CHIMERIC ENGULFMENT RECEPTOR MOLECULES

Abstract

The present disclosure relates to chimeric engulfment receptor molecules, host cells modified to include the phagocytic engulfment molecules, and methods of making and using such receptor molecules and modified cells.

Description

STATEMENT REGARDING SEQUENCE LISTING

[0001] The Sequence Listing associated with this application is provided in text format in lieu of a paper copy, and is hereby incorporated by reference into the specification.

[0002] The name of the text file containing the Sequence Listing is 200265_401WO_SEQUENCE_LISTING.txt. The text file is 275 KB, was created on Sep. 26, 2017, and is being submitted electronically via EFS-Web.

BACKGROUND

[0003] There are two principle types of phagocytosis, which are influenced by the target, cell-type and surrounding milieu. Anti-microbe phagocytosis clears and degrades disease-causing microbes, induces pro-inflammatory signaling through cytokine and chemokine secretion, and recruits immune cells to mount an effective inflammatory response. This type of phagocytosis is often referred to as "inflammatory phagocytosis" (or "immunogenic phagocytosis"). However, in some instances, such as with certain persistent infections, anti-inflammatory responses may follow microbial uptake. Anti-microbe phagocytosis is commonly performed by professional phagocytes of the myeloid lineage, such as immature dendritic cells (DCs) and macrophages and by tissue-resident immune cells.

[0004] Phagocytosis of damaged, self-derived apoptotic cells or cell debris (e.g., efferocytosis), in contrast, is typically a non-inflammatory (also referred to as a "non-immunogenic") process. Billions of damaged, dying, and unwanted cells undergo apoptosis each day. Unwanted cells include, for example, excess cells generated during development, senescent cells, infected cells (intracellular bacteria or viruses), transformed or malignant cells, and cells irreversibly damaged by cytotoxic agents. Phagocytes execute specific, swift removal of apoptotic cells without causing damage to the surrounding tissues or inducing a pro-inflammatory immune response. Steps for apoptotic cell clearance include: (1) release of "find me" signals from apoptotic cells to recruit phagocytes to the location of apoptotic cells; (2) "eat me" signals exposed on the surface of apoptotic cells are bound by phagocytes via specific receptors; (3) cytoskeletal rearrangement to engulf the apoptotic cell; and (4) the ingested apoptotic cell is digested and specific phagocytic responses are elicited (e.g., secretion of anti-inflammatory cytokines).

[0005] There is an ongoing need for new compositions and methods of treating infections, inflammatory diseases, immune diseases, and various cancers. The methods and compositions disclosed herein meets such needs by enhancing the removal of infected, transformed, malignant, apoptotic, damaged or necrotic cells or particles from the body in treatment of various cancers, acute and chronic infections, inflammatory, immune and selected neurological diseases.

BRIEF SUMMARY

[0006] Chimeric, engulfment receptors are described herein. In certain embodiments, the chimeric engulfment receptors ("CER" in the singular and "CERs" in the plural) include an extracellular domain, a transmembrane domain, and an intracellular engulfment signaling domain. The transmembrane domain is positioned between and connects the extracellular domain and the engulfment signaling domain. The extracellular domain comprises a binding domain and an optional extracellular spacer domain positioned between and connecting the binding domain and transmembrane domain. In certain embodiments, the chimeric engulfment receptors described herein are chimeric proteins having (a) and extracellular domain that targets a pro-engulfment marker or a target antigen associated with a disease, disorder, condition, or infection, (b) a transmembrane domain, and (c) an engulfment signaling domain. In certain embodiments, the engulfment signaling domain comprises at least one of a homeostatic engulfment domain and a pro-inflammatory engulfment domain. In some embodiments, the engulfment signaling domain comprises a primary engulfment signaling domain and a secondary engulfment signaling domain. In particular embodiments, the chimeric engulfment receptors are single chain chimeric proteins. Chimeric engulfment receptors may be designed to generate an inflammatory response to a target cell/organ/tissue/area. While apoptotic cell clearance is typically a non-inflammatory process, inflammation can be beneficial to the host in certain contexts, such as, for example, in the context clearance of apoptotic tumor cells to induce an immune response to residual tumor cells.

[0007] In some embodiments, the extracellular domain of the CER includes a binding domain specific to a pro-engulfment marker. In certain such embodiments, the extracellular domain includes a phosphatidylserine (PtdSer) binding domain. In embodiments of the CERs described herein, a PtdSer binding domain can include all or a portion of the extracellular domain of T cell immunoglobulin and mucin domain 1 (Tim1), T cell immunoglobulin and mucin domain 4 (Tim4), or T cell immunoglobulin and mucin domain 3 (Tim3). In other embodiments a PtdSer binding domain can include all or a portion of a binding domain derived from FA58C2, GAS6, protein S, Factor VII, Factor IX, Factor X, or prothrombin PS.

[0008] In further embodiments, the extracellular domain binds to a target antigen. In certain such embodiments, the extracellular domain includes all or part of the extracellular domain of an Fc receptor (FcR), such as, for example, FcGR1, FcGR2A, FcGR2B2, FcGR2C, FcGR3A, Fc.epsilon.R1, and Fc.alpha.R1. In still other embodiments where the extracellular domain binds a target antigen, the extracellular domain can include an antibody or an antigen-binding domain thereof. For example, the extracellular domain can include an antibody or an antigen-binding domain selected from intrabodies, peptibodies, nanobodies, single domain antibodies, SMIPs, and multispecific antibodies. In certain such embodiments, the extracellular domain includes a Fab binding domain. In yet other such embodiments, the extracellular domain includes a scFv.

[0009] Upon binding of the extracellular domain of the CER to the pro-engulfment marker or targeted antigen, the engulfment signaling domain of the CER stimulates engulfment signaling activity. Thus, upon activation, the engulfment signaling domain included in the CER transduces effector functional signals that direct the host cell to engulf. In certain embodiments, the engulfment signaling domain of the CER includes a homeostatic engulfment signaling domain. Examples of homeostatic engulfment signaling domains include MRC1, ItgB5, MERTK, Tyro3, and Axl signaling domains. In other embodiments, the engulfment signaling domain includes a pro-inflammatory engulfment signaling domain. Examples of pro-inflammatory engulfment signaling domains include Traf6, Syk, MyD88, Zap70, Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R, NFAM1, DAP12, and CD79b signaling domains. In still other embodiments, the engulfment signaling domain includes a primary engulfment signaling domain and a secondary engulfment signaling domain. In such embodiments, the primary engulfment signaling domain and the secondary engulfment signaling domain can be independently selected from homeostatic and pro-inflammatory engulfment signaling domains, including those described herein.

[0010] In further aspects, the present disclosure is directed to cells genetically modified to express a CER. In specific embodiments, the CER confers and engulfment phenotype not exhibited by a single, naturally-occurring receptor protein. In other embodiments, CER according to the present description confers an engulfment phenotype to a cell that does not naturally exhibit engulfment activity. In certain embodiments, cells are genetically modified to express a CER that targets a pro-engulfment marker associated with dead, dying, damaged, infected, or necrotic cells. In other embodiments, cells are genetically modified to express a CER that targets a marker, such as an antibody, associated with an infectious microbe or molecule induced by an infectious particle. In such embodiments, the genetically modified cells promote clearance or degradation of the targeted cells or microbes upon binding by the CER of the marker associated with the targeted infectious microbe or the targeted molecule induced by an infectious particle. In other specific embodiments, cells are genetically modified to express a CER that targets an antigenic marker that does not normally trigger engulfment. For example, in such embodiments, the extracellular domain of the CER can include an antibody or antigen-binding portion of an antibody, such as a Fab binding domain or a scFv specific to an antigenic marker. In certain such embodiments, the antigenic marker can be a surface protein, glycoprotein, or glycolipid characteristic of aberrant cells associated with a disease, disorder, or other undesirable condition. In such embodiments, the genetically modified cells promote clearance or degradation of the aberrant cells upon binding of the antigenic marker by the CER.

[0011] In further embodiments, a CER-modified cell may be further modified to co-express a small GTPase. A small GTPase may be introduced into a CER-modified cell using a vector encoding bot the CER and the small GTPase. Alternatively, a small GTPase may be introduced into a cell that is or will be a CER-modified cell using a vector different than the vector used to introduce the CER.

[0012] In yet further aspects, the present disclosure is directed to a method treating a subject suffering from a disease, disorder or undesired condition. Embodiments of these methods include administering to a subject a therapeutically effective amount of a pharmaceutical composition including one or more CERs or a population of cells genetically modified to express one or more CERs according to the present description.

[0013] In other aspects, the present disclosure provides methods for altering the engulfment phenotype of a host cell. In certain embodiments, such methods include one or more of the following: methods for producing a population of cells exhibiting an engulfment phenotype by introducing into and expressing a CER in host cells that do not naturally exhibit an engulfment phenotype; methods for altering the engulfment phenotype of a population of cells by introducing into and expressing a CER in the host cells, wherein the CER confers an engulfment phenotype specific to a pro-engulfment marker or antigenic marker that is not naturally targeted by the host cells; and methods for enhancing the engulfment phenotype of a population of cells by introducing into and expressing a CER in the host cells, where the CER is specific to a pro-engulfment marker or antigenic marker naturally targeted by the host cells and expression of the CER by the host cells enhances the engulfment by the host cells of cells, microbes, or particles exhibiting the targeted pro-engulfment or antigenic marker.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIGS. 1A-1D show illustrative schematics of chimeric engulfment receptors (CERs). FIG. 1A shows two illustrative CERs having extracellular domains specific for phosphatidylserine (Tim4 and scFv) and table include a single engulfment signaling domain. FIG. 1B shows two illustrative CERs having binding domains specific for phosphatidylserine (Tim4 and scFv) and include an engulfment signaling domain that includes a primary engulfment signaling domain and a secondary engulfment signaling domain. Integration of an accessory or secondary engulfment signaling domain into a CER may enhance engulfment responses even in the absence of expressed ligands for accessory receptors. FIG. 1C shows two illustrative CERs having extracellular domains comprising a Fab or FcR and include a single engulfment signaling domain. FIG. 1D shows two illustrative CERs having comprising a Fab or FcR and include an engulfment signaling domain that includes a primary engulfment signaling domain and a secondary engulfment signaling domain. "TMD"=transmembrane domain.

[0015] FIGS. 2A and 2B show illustrative CER vectors. The CER vectors shown in FIG. 2A contain a single engulfment signaling domain. The CER vectors shown in FIG. 2B contain an engulfment signaling domain that includes a primary engulfment signaling domain and a secondary engulfment signaling domain. "ECD"=extracellular domain.

[0016] FIGS. 3A and 3B show a comparison of a natural lymphocyte and a lymphocyte modified with a CER of the present disclosure. FIG. 3A shows an endogenous lymphocyte. FIG. 3B shows a lymphocyte modified with a CER of the present disclosure.

[0017] FIG. 4 shows an illustrative method of administration of the CERs of the present disclosure.

[0018] FIGS. 5A-5C show illustrative treatment timelines. FIG. 5A shows a treatment scheme for therapy with cells modified with a CER. FIG. 5B shows a treatment scheme for CER-modified cells used in combination with non-phagocytic T cellular immune therapies. FIG. 5C shows a treatment scheme for CER-modified cells used in combination with monoclonal antibodies, conventional chemotherapy, or radiation therapy.

[0019] FIGS. 6A-6F show Tim4-MERTK chimeric engulfment receptor (CER) mediated in vitro engulfment of apoptotic target cells. FIG. 6A shows an illustrative schematic of Tim4-MERTK CER. ECD=extracellular domain; TMD=transmembrane domain; ESD=engulfment signaling domain. FIG. 6B shows a fluorescence-activated cell sorting (FACs) plot of murine Ba/F3 B-cells transduced with pMSCV retroviral vector comprising a nucleotide sequence encoding the Tim4-MERTK CER of FIG. 6A and a nucleotide sequence encoding green fluorescent protein (GFP). Positive Ba/F3 B-cell transductants were sorted by staining for green fluorescent protein marker and Tim4 using flow cytometry, demonstrating the presence of the Tim4-MERTK CER on the cellular membrane of Ba/F3 B-cells. FIG. 6C shows a bar graph of phagocytosis of apoptotic primary thymocytes by Tim4-MERTK chimeric engulfment receptor-expressing Ba/F3 B-cells at 2 hours and 24 hours post-incubation as quantified by FACs. BA/F3 B-cells transduced with pMSCV comprising nucleotide sequence encoding Tim4 and GFP were used as a negative control. FIG. 6D shows a line graph illustrating the correlation between quantity of Tim4-MERTK CER surface expression, as well as duration of target cell incubation, with phagocytosis of apoptotic primary thymocytes. FIG. 6E shows an image from fluorescence microscopy, showing that Tim4-MERTK CER-expressing cells engulf pHrodo Red dye-stained apoptotic primary thymocytes. Yellow triangles indicate apoptotic primary thymocytes inside phagolysosomes; white squares indicate low intensity staining of un-engulfed apoptotic primary thymocytes. FIG. 6F shows FACs and histogram plots of Ba/F3 cells that are double positive for pHrodo Red and Tim4-MERTK CER expression, demonstrating in vitro phagocytosis.

[0020] FIGS. 7A-7B show Tim4-MERTK chimeric engulfment receptor (CER)-mediated engulfment of apoptotic target cells. FIG. 7A shows time-lapse images of Tim4-MERTK CER-mediated clearance of target apoptotic thymocytes at 12 hours and 48 hours incubation time. Greater than 95% of target cells had been eliminated within four days. Sheets of apoptotic thymocytes persist in the presence of control Ba/F3 cells expressing Tim4 (bottom panel) (white arrows point to thymocytes). FIG. 7B shows a line graph quantifying the number of thymocytes present per high power microscopic field in control (Tim4 expressing Ba/F3 cells) and Tim4-MERTK CER-expressing Ba/F3 cells samples. FIG. 7B demonstrates essentially complete elimination of the apoptotic thymocytes by the lymphocytes expressing the Tim4-MERTK CER.

[0021] FIGS. 8A-8C show Tim4-MERTK chimeric engulfment receptor-mediated clearance of Raji Burkitt's lymphoma cells. FIG. 8A shows a FACs plot of Ba/F3 cells that are double positive for pHrodo Red and Tim4-MERTK CER expression, demonstrating in vitro phagocytosis, and FIG. 8B shows a bar graph of phagocytosis of Raji Burkitt's lymphoma cells by Tim4-MERTK CER-expressing Ba/F3 B-cells as compared to control Ba/F3 B-cells expressing Tim4. FIG. 8C shows a fluorescence micrograph of Tim4-MERTK CER-mediated clearance of Raji Burkitt's lymphoma cells.

[0022] FIGS. 9A-9F show FA58C2-MERTK chimeric engulfment receptor (CER)-mediated in vitro engulfment of apoptotic target cells. FIG. 9A shows an illustrative schematic of FA58C2-MERTK CER. FIG. 9B shows a bar graph of phagocytosis of apoptotic primary thymocytes by FA58C2-MERTK CER-expressing Ba/F3 B-cells at 2 hours and 24 hours post-incubation as quantified by FACs. BA/F3 B-cells transduced with pMSCV comprising a nucleotide sequence encoding Tim4 and GFP were used as a negative control. FIG. 9C shows a line graph illustrating the correlation between quantity of FA58C2-MERTK CER surface expression, as well as duration of target cell incubation, with phagocytosis of apoptotic primary thymocytes. FIG. 9D shows an image from fluorescence microscopy, showing that FA58C3-MERTK CER-expressing cells engulf pHrodo Red dye-stained apoptotic primary thymocytes. Yellow triangles indicate apoptotic primary thymocytes inside phagolysosomes. FIG. 9E shows a FACs plot and FIG. 9F shows a histogram plot of Ba/F3 cells that are double positive for pHrodo Red and FA58C2-MERTK CER expression, demonstrating in vitro phagocytosis.

[0023] FIGS. 10A-10E show enhancement of CER-mediated phagocytosis by small GTPase Rac1. FIG. 10A shows an illustrative schematic of a bi-cistronic retroviral expression cassette for FA58C2-MERTK CER and Rac1 or Rab5 separated by P2A sequence (top panel) and a resulting co-expressed FA58C2-MERTK CER and GTPase (Rac1) (bottom panel). FIG. 10B shows a line graph illustrating the correlation between quantity of FA58C2-MERTK CER surface expression with phagocytosis of apoptotic primary thymocytes at 24 hours incubation in Ba/F3 B-cells expressing FA58C2-MERTK CER or FA58C2-MERTK CER+Rac1. FIG. 10C shows an image from fluorescence microscopy, showing that FA58C3-MERTK CER+Rac1-expressing cells engulf pHrodo Red dye-stained apoptotic primary thymocytes. FIG. 10D shows a FACs plot and FIG. 10E shows a histogram plot of Ba/F3 cells that are double positive for pHrodo Red and FA58C2-MERTK CER+Rac1 expression, demonstrating in vitro phagocytosis.

[0024] FIGS. 11A-11E show FA58C2-Syk CER-mediated in vitro engulfment of target apoptotic cells. FIG. 11A shows an illustrative schematic of a retroviral expression cassette for FA58C2-Syk CER and a bi-cistronic retroviral expression cassette for FA58C2-Syk CER and small GTPase Rac1 separated by P2A sequence (top panel) and a resulting co-expressed FA58C2-Syk CER and Rac1 (bottom panel). FIG. 11B shows a bar graph of phagocytosis of apoptotic primary thymocytes by FA58C2-Syk CER- or FA58C2-Syk CER+Rac1-expressing Ba/F3 B-cells at 2 hours and 24 hours post-incubation as quantified by FACs. BA/F3 B-cells transduced with pMSCV comprising a nucleotide sequence encoding Tim4 and green fluorescent protein were used as a negative control. FIG. 11C shows a line graph illustrating the correlation between quantity of FA58C2-Syk CER surface expression with phagocytosis of apoptotic primary thymocytes at 24 hours incubation in Ba/F3 B-cells expressing FA58C2-Syk CER or FA58C2-Syk CER+Rac1. The addition of small GTPase Rac1 enhances phagocytosis. FIG. 11D shows an image from fluorescence microscopy, showing that FA58C3-Syk CER+Rac1-expressing cells engulf pHrodo Red dye-stained apoptotic primary thymocytes. Yellow triangles indicate apoptotic primary thymocytes inside phagolysosomes. FIG. 11E shows a FACs plot of Ba/F3 cells that are double positive for pHrodo Red and FA58C2-Syk CER+Rac1 expression, demonstrating in vitro phagocytosis.

[0025] FIGS. 12A-12D show that co-expression of small GTPase Rab5 enhances CER-mediated phagocytosis. FIG. 12A shows an illustrative schematic of a bi-cistronic retroviral expression cassette for FA58C2-Syk CER and small GTPase Rab5 separated by P2A sequence (top panel) and a resulting co-expressed FA58C2-Syk CER and Rab5 (bottom panel). FIG. 12B shows a bar graph of phagocytosis of apoptotic primary thymocytes by FA58C2-Syk CER- or FA58C2-Syk CER+Rab5-expressing Ba/F3 B-cells at 2 hours post-incubation as quantified by FACs. BA/F3 B-cells transduced with pMSCV comprising a nucleotide sequence encoding Tim4 and GFP were used as a negative control. FIG. 12C shows an image from fluorescence microscopy, showing that FA58C3-Syk CER+Rab5-expressing cells engulf pHrodo Red dye-stained apoptotic primary thymocytes. FIG. 12D shows FACs plots of Ba/F3 cells that are double positive for pHrodo Red and FA58C2-Syk CER (left plot), FA58C2-Syk CER+Rab5 expression (middle plot), or Tim4 control, demonstrating in vitro phagocytosis for FA58C2-Syk CER expressing cells (9%) and increased phagocytosis with the addition of Rab5 (12.5%).

[0026] FIGS. 13A-13H show CD19-MERTK chimeric engulfment receptor (CER)-mediated in vitro engulfment of target B-cells. FIG. 13A shows an illustrative schematic of a retroviral expression cassette for CD19-MERTK CER (top panel) and the resulting co-expressed CD19-MERTK CER (bottom panel). FIG. 13B shows an illustrative schematic of a retroviral expression cassette for a bi-cistronic retroviral expression cassette for CD19-MERTK CER and small GTPase Rac1 separated by P2A sequence (top panel) and the resulting co-expressed CD19-MERTK CER and Rac1 (bottom panel). FIG. 13C shows a bar graph of phagocytosis of Raji Burkitt's lymphoma cells by CD19-MERTK CER- or CD19-MERTK CER+Rac1-expressing Ba/F3 B-cells at 2 hours and 24 hours post-incubation as quantified by FACs. Ba/F3 B-cells transduced with pMSCV comprising a nucleotide sequence encoding Tim4 and GFP were used as a negative control. FIG. 13D shows a line graph illustrating the correlation between quantity of CD19-MERTK CER surface expression with phagocytosis of Raji Burkitt's lymphoma cells at 24 hours incubation in Ba/F3 B-cells expressing CD19-MERTK CER. FIG. 13E shows an image from fluorescence microscopy, showing that CD19-MERTK CER+Rac1-expressing cells engulf pHrodo Red dye-stained Raji Burkitt's lymphoma cells. Yellow triangles indicate Raji Burkitt's lymphoma cells inside phagolysosomes. FIG. 13F shows a FACs plot of Ba/F3 cells that are double positive for pHrodo Red and CD19-MERTK CER expression, demonstrating in vitro phagocytosis at 2 hours incubation with Raji Burkitt's lymphoma target cells or at 24 hours incubation with Raji Burkitt's lymphoma target cells (FIG. 13G). FIG. 13H shows a fluorescent microscope image of CD19-MERTK CER expressing cells that engulfed pHrodo Red dye stained Raji Burkitt's lymphoma cells. White arrows indicate engulfment events.

[0027] FIG. 14 shows Tables 1 and 2, which illustrate examples of CERs according the present disclosure.

[0028] FIG. 15 shows Table 3, which illustrates examples of CERs according the present disclosure.

[0029] FIG. 16 shows a vector map for a lentiviral vector comprising "CER01" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:71. CER01 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and a MERTK signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER01 sequence by a viral T2A sequence.

[0030] FIGS. 17A-D show FACS purification of Ba/F3 murine cells transduced with CER01. Biotin-labeled cetuximab (anti-EGFR antibody) followed by streptavidin conjugated with R-phycoerythrin (SA-PE) were used to detect EGFR expression by FACS in untransduced Ba/F3 cells (FIG. 17A) and Ba/F3 murine B cells transduced with the CER01-T2A-EGFRt containing lentivirus (FIG. 17B) at 48 hours post-transduction. CER+EGFRt+ expressing cells (FIG. 17C) were selected by FACs and expanded for downstream assays. FIG. 17D shows untransduced Ba/F3 control cells following EGFRt purification.

[0031] FIGS. 18A-B show in vitro engulfment of dexamethasone-treated thymocytes by CER01+ Ba/F3 murine B cells. FIG. 18A shows fluorescent microscope images of Ba/F3 cells transduced with EGFRt+ control co-cultured with dexamethasone-treated thymocytes; FIG. 18B shows fluorescent microscope images of Ba/F3 cells transduced with CER01 co-cultured with dexamethasone-treated thymocytes (white arrows indicate engulfment events). A high magnification image of a portion of FIG. 18B is shown to the right.

[0032] FIGS. 19A-B show FACS analysis of CER01+ Ba/F3 effector cells (FIG. 19A) and quantification of engulfment of dexamethasone-treated thymocytes by CER01+ Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 19B).

[0033] FIGS. 20A-B depict phagocytic index for CER01+ cells or EGFRt+ control Ba/F3 cells. FIG. 20A shows a table of values for percentage of phagocytosing cells and hybrid capture values of CER01+ cells or EGFRt+ control Ba/F3 cells co-cultured with dexamethansone-treated thymocytes. FIG. 20B shows a graph of phagocytic index for CER01+ cells or EGFRt+ control Ba/F3 cells.

[0034] FIG. 21 shows a fluorescent microscope image of phagocytosis of CT26 colon carcinoma cells by CER01+ Ba/F3 cells. White arrows indicate phagocytosis events.

[0035] FIGS. 22A-B--a hybrid capture algorithm was used to detect fluorescence of pHrodo Red stained target cells within CER01+ Ba/F3 cells CELLTRACE Violet stained area on fluorescent images of phagocytosis assay. FIG. 22A shows a histogram plot of hybrid cell counts extracting CT26 target cell area from CER01+ Ba/F3 cells, and FIG. 22B shows hybrid cell counts for EGFRt+ control Ba/F3 cells. The area ratio represents the overlay area of CT26 cells within Ba/F3 cells.

[0036] FIG. 23 shows a scatterplot of hybrid cell counts extracting CT26 target cell area from CER01+ Ba/F3 cells or EGFRt+ control Ba/F3 cells. The area ratio represents the overlay area of CT26 cells within Ba/F3 cells.

[0037] FIGS. 24A-B show frequency of phagocytosis (A) and phagocytic index (B) of CER01+ Ba/F3 cells or EGFRt+ control Ba/F3 cells co-cultured with CT26 colon carcinoma cells.

[0038] FIG. 25 shows a fluorescent microscope image of phagocytosis of A20 lymphoma cells by CER01+ Ba/F3 cells. White arrows indicate phagocytosis events.

[0039] FIGS. 26A-B--a hybrid capture algorithm was used to detect fluorescence of pHrodo Red stained target cells within CER01+ Ba/F3 cells CELLTRACE Violet stained area on fluorescent images of phagocytosis assay. FIG. 26A shows a histogram plot of hybrid cell counts extracting A20 target cell area from CER01+ Ba/F3 cells, and FIG. 26B shows hybrid cell counts for EGFRt+ control Ba/F3 cells. The area ratio represents the overlay area of A20 cells within Ba/F3 cells.

[0040] FIG. 27 shows a scatterplot of hybrid cell counts extracting A20 target cell area from CER01+ Ba/F3 cells or EGFRt+ control Ba/F3 cells. The area ratio represents the area of A20 cells within Ba/F3 cells.

[0041] FIG. 28 show a graph of phagocytic index of CER01+ Ba/F3 cells or EGFRt+ control Ba/F3 cells co-cultured with A20 cells.

[0042] FIG. 29 shows a microscope image of phagocytosis of WR19L T cell lymphoma cells by CER01+ Ba/F3 cells. White arrows indicate phagocytosis events.

[0043] FIG. 30 shows a graph of frequency of phagocytosis of WR19L cells by CER01+ Ba/F3 cells.

[0044] FIGS. 31A-B show transduction and expansion of CER01+ human primary B cells. FIG. 31A shows FACS analysis of human primary B cells transduced with CER01 (right histogram) and control B cells (left histogram) using an anti-EGFR antibody and then an anti-Tim4 Kat5-18 antibody. FIG. 31B shows purified CER01+ B cells that were expanded at 24 hours, 48 hours and 72 hours.

[0045] FIGS. 32A-B shows fluorescent microscope images of in vitro phagocytosis of staurosporine treated Jurkat cells by CER01+ human primary B cells (FIG. 32A) compared to control human primary B cells transduced with truncated EGFR (FIG. 32B). White arrows indicate phagocytosis events.

[0046] FIG. 33 shows phagocytosis of staurosporine treated, pHrodo Red stained Jurkat cells by CER01+ human primary B cells as analyzed by FACS. Gating was performed on viable CD19+, allophycocyanin (APC)-labeled cells (left plot) and frequency of double positive stained events (APC and pHrodo Red) was defined as phagocytosis events (right plot).

[0047] FIG. 34 shows a graph of frequency of phagocytosis of staurosporine treated Jurkat cells co-incubated with CER01+ human primary B cells.

[0048] FIG. 35 shows fluorescent microscope images of in vitro phagocytosis of oxaliplatin and fluorouracil treated Jurkat cells by CER01+ human primary B cells. White arrows indicate phagocytosis events.

[0049] FIG. 36 shows a vector map for a lentiviral vector comprising "CER08" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:83. CER08 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and a Tyro3 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER08 sequence by a viral T2A sequence.

[0050] FIGS. 37A-B show FACS plots of viable, CER08+ modified Ba/F3 cells (FIG. 37A) and cell populations staining double positive for pHrodo red and CELLTRACE Violet representing frequency of phagocytosis (FIG. 37B) in a co-culture of dexamethasone treated, pHrodo Red stained thymocytes with CELLTRACE Violet stained, CER08+ mouse Ba/F3 cells.

[0051] FIG. 38 shows fluorescent microscope images of phagocytosis of dexamethasone treated thymocytes by CER08+Ba/F3 cells (lower photo) as compared to EGFRt+Ba/Fe control cells (upper photo). White arrows indicate phagocytosis events. High magnification of an engulfment event is shown on the right.

[0052] FIGS. 39A-B show phagocytic index for CER08+ cells or EGFRt+ control Ba/F3 cells. FIG. 39A shows a table of values for percentage of phagocytosing cells and hybrid capture values of CER08+ cells or EGFRt+ control Ba/F3 cells co-cultured with dexamethansone-treated thymocytes. FIG. 39B shows a graph of phagocytic index for CER08+ cells or EGFRt+ control Ba/F3 cells.

[0053] FIG. 40 shows a vector map for a lentiviral vector comprising "CER09" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:84. CER09 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and a DAP12 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER09 sequence by a viral T2A sequence.

[0054] FIGS. 41A-B show FACS plots of viable, CER09+ modified Ba/F3 cells (FIG. 41A) and cell populations staining double positive for pHrodo red and CELLTRACE Violet representing frequency of phagocytosis (FIG. 41B) in a co-culture of dexamethasone treated, pHrodo Red stained thymocytes with CELLTRACE Violet stained, CER09+ mouse Ba/F3 cells.

[0055] FIGS. 42A-B show fluorescent microscope images of phagocytosis of dexamethasone treated thymocytes by CER09+Ba/F3 cells (FIG. 42B) as compared to EGFRt+Ba/Fe control cells (FIG. 42A). White arrows indicate phagocytosis events. High magnification of an engulfment event is shown on the right.

[0056] FIGS. 43A-B show phagocytic index for CER09+ cells or EGFRt+ control Ba/F3 cells. FIG. 43A shows a table of values for percentage of phagocytosing cells and hybrid capture of CER09+ cells or EGFRt+ control Ba/F3 cells co-cultured with dexamethansone-treated thymocytes. FIG. 43B shows a graph of phagocytic index for CER09+ cells or EGFRt+ control Ba/F3 cells.

[0057] FIGS. 44A-B show fluorescent microscope images of in vitro phagocytosis of staurosporine treated CT26 colon carcinoma cells by CER09+Ba/F3 cells (FIG. 44A) and EGFRt+ control Ba/F3 cells. White arrows indicate phagocytosis events.

[0058] FIG. 45 shows a scatterplot of hybrid cell counts extracting CT26 target cell area from CER09+Ba/F3 cells or EGFRt+ control Ba/F3 cells. The area ratio represents the area of CT26 cells within Ba/F3 cells.

[0059] FIG. 46 shows phagocytic index for CER09+ cells or EGFRt+ control Ba/F3 cells co-incubated with staurosporine treated CT26 cells.

[0060] FIG. 47 shows a fluorescent microscope image of in vitro phagocytosis of staurosporine treated WR19L lymphoma cells by CER09+Ba/F3 cells. White arrows indicate phagocytosis events.

[0061] FIG. 48 shows a fluorescent microscope image of in vitro phagocytosis of staurosporine treated A20 lymphoma cells by CER09+Ba/F3 cells. White arrows indicate phagocytosis events.

[0062] FIGS. 49A-B show transduction and expansion of CER09+ human primary B cells. FIG. 49A shows FACS analysis of human primary B cells transduced with CER09 (right histogram) and control B cell (left histogram) using an anti-EGFR antibody and then an anti-Tim4 Kat5-18 antibody. FIG. 49B shows purified CER09+ B cells that were expanded at 24 hours, 48 hours and 72 hours.

[0063] FIG. 50 shows phagocytosis of staurosporine treated, pHrodo Red stained Jurkat cells by CER09+ human primary B cells as analyzed by FACS. Gating was performed on viable CD19+, allophycocyanin (APC)-labeled cells (left plot) and frequency of double positive stained events (APC and pHrodo Red) was defined as phagocytosis events (right plot).

[0064] FIG. 51 shows a graph of frequency of phagocytosis of staurosporine treated Jurkat cells by CER09+ human primary B cells or control EGFRt+ human primary B cells.

[0065] FIG. 52 shows fluorescent microscope images of in vitro phagocytosis of staurosporine treated Jurkat cells by CER09+ human primary B cells (left photo) or EGFRt+ human primary B cells (right photo). White arrows indicate phagocytosis events.

[0066] FIG. 53 shows a vector map for a lentiviral vector comprising "CER10" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:86. CER10 comprises a Tim4 binding domain, a Dap12 transmembrane domain, and a DAP12 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER10 sequence by a viral P2A sequence.

[0067] FIGS. 54A-B show FACS analysis of viable, CER10+ Ba/F3 effector cells (FIG. 54A) and quantification of engulfment of dexamethasone-treated thymocytes by CER10+ Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 54B).

[0068] FIGS. 55A-B show fluorescent microscope images of in vitro phagocytosis of dexamethasone treated thymocytes by CER10+ Ba/F3 cells (FIG. 55B) or control EGFRt+Ba/F3 cells (FIG. 55A). White arrows indicate phagocytosis events. High magnification of an engulfment event is shown on the right.

[0069] FIGS. 56A-B show phagocytic index for CER10+ cells or EGFRt+ control Ba/F3 cells. FIG. 56A shows a table of values for percentage of phagocytosing cells and hybrid capture values of CER10+ cells or EGFRt+ control Ba/F3 cells co-cultured with dexamethansone-treated thymocytes. FIG. 56B shows a graph of phagocytic index for CER10+ cells or EGFRt+ control Ba/F3 cells.

[0070] FIG. 57 shows a vector map for a lentiviral vector comprising "CER11" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:87. CER11 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and an Axl signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO:121), which is separated from the CER11 sequence by a viral T2A sequence.

[0071] FIGS. 58A-B show FACS analysis of CER11+Ba/F3 effector cells (FIG. 58A) and quantification of engulfment of dexamethasone-treated thymocytes by CER11+ Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 58B).

[0072] FIGS. 59A-B show fluorescent microscope images of in vitro phagocytosis of dexamethasone treated thymocytes by CER11+Ba/F3 cells (FIG. 59B) or control EGFRt+Ba/F3 cells (FIG. 59A). White arrows indicate phagocytosis events. High magnification of an engulfment event is shown on the right.

[0073] FIGS. 60A-B show phagocytic index for CER11+ cells or EGFRt+ control Ba/F3 cells. FIG. 60A shows a table of values for percentage of phagocytosing cells and hybrid capture values of CER11+ cells or EGFRt+ control Ba/F3 cells co-cultured with dexamethansone-treated thymocytes. FIG. 60B shows a graph of phagocytic index for CER11+ cells or EGFRt+ control Ba/F3 cells.

[0074] FIGS. 61A-B show fluorescent microscope images of in vitro phagocytosis of staurosporine treated CT26 colon carcinoma cells by CER11+Ba/F3 cells (left photo) or control EGFRt+Ba/F3 cells (right photo). White arrows indicate phagocytosis events.

[0075] FIG. 62 shows a scatterplot of hybrid cell counts extracting CT26 target cell area from CER11+Ba/F3 cells or EGFRt+ control Ba/F3 cells. The area ratio represents the area of CT26 cells within Ba/F3 cells.

[0076] FIG. 63 shows fluorescent microscope image showing in vitro phagocytosis of WR19L cells by CER11+Ba/F3. White arrow shows phagocytosis event.

[0077] FIGS. 64A-B show FACS analysis of CER11+Ba/F3 effector cells (FIG. 64A) and quantification of engulfment of WR19L lymphoma cells by CER11+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 64B).

[0078] FIGS. 65A-B show fluorescent microscope images of in vitro phagocytosis of staurosporine treated A20 lymphoma cells by CER11+Ba/F3 cells (left photo) or control EGFRt+Ba/F3 cells (right photo). White arrows indicate phagocytosis events.

[0079] FIG. 66 shows phagocytic index for CER11+ cells or EGFRt+ control Ba/F3 cells co-incubated with staurosporine treated A20 cells.

[0080] FIG. 67 shows fluorescent microscope images of in vitro phagocytosis of oxaliplatin and fluorouracil treated Jurkat cells by CER11+ human primary B cells (left photo) or control EGFRt+ human primary B cells (right photo). White arrows indicate phagocytosis events.

[0081] FIG. 68 shows fluorescent microscope images of in vitro phagocytosis of gemcitabine treated COLO320HSR colon cancer cells by CER11+ human primary B cells. White arrows indicate phagocytosis events.

[0082] FIG. 69 shows fluorescent microscope images of in vitro phagocytosis of paclitaxel or paclitaxel treated A204 rhabdomyosarcoma cells by CER11+ human primary B cells. Arrows indicate phagocytosis events.

[0083] FIG. 70 shows fluorescent microscope images of in vitro phagocytosis of paclitaxel or paclitaxel+gemcitabine treated H1703 non small cell lung cancer cells by CER11+ human primary B cells. Arrows indicate phagocytosis events.

[0084] FIG. 71 shows a vector map for a lentiviral vector comprising "CER12" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:90. CER12 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and an Fc.epsilon.RI.gamma. signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER12 sequence by a viral T2A sequence.

[0085] FIGS. 72A-B show FACS analysis of CER12+Ba/F3 effector cells (FIG. 72A) and quantification of engulfment of thymocytes by CER12+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 72B).

[0086] FIGS. 73A-B show fluorescent microscope images of in vitro phagocytosis of dexamethasone treated thymocytes by CER12+Ba/F3 cells (FIG. 73B) or control EGFRt+Ba/F3 cells (FIG. 73A). White arrows indicate phagocytosis events. High magnification of an engulfment event is shown on the right.

[0087] FIGS. 74A-B show phagocytic index for CER12+ cells or EGFRt+ control Ba/F3 cells. FIG. 74A shows a table of values for percentage of phagocytosing cells and hybrid capture values of CER12+ cells or EGFRt+ control Ba/F3 cells co-cultured with dexamethansone-treated thymocytes. FIG. 74B shows a graph of phagocytic index for CER12+ cells or EGFRt+ control Ba/F3 cells.

[0088] FIG. 75 shows a fluorescent microscope image of in vitro phagocytosis of staurosporine treated WR19L lymphoma cells by CER12+Ba/F3 cells. White arrows indicate phagocytosis events.

[0089] FIG. 76 shows a fluorescent microscope image of in vitro phagocytosis of staurosporine treated A20 lymphoma cells by CER12+Ba/F3 cells. The white arrow indicates a phagocytosis event.

[0090] FIG. 77 shows phagocytic index for CER12+ cells or EGFRt+ control Ba/F3 cells co-incubated with staurosporine treated A20 cells.

[0091] FIG. 78 shows a vector map for a lentiviral vector comprising "CER13" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:91. CER13 comprises a Tim4 binding domain, an Fc.epsilon.RI.gamma. transmembrane domain, and an Fc.epsilon.RI.gamma. signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER13 sequence by a viral T2A sequence.

[0092] FIGS. 79A-B show FACS analysis of CER13+Ba/F3 effector cells (FIG. 79A) and quantification of engulfment of thymocytes by CER13+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 79B).

[0093] FIG. 80 shows fluorescent microscope images of in vitro phagocytosis of paclitaxel and gemcitabine treated Colo320 HSR colon cancer cells by CER13+ human primary B cells. Arrows indicate phagocytosis events.

[0094] FIG. 81 shows fluorescent microscope images of in vitro phagocytosis of paclitaxel treated A204 rhabdomyosarcoma cells by CER13+ human primary B cells. Arrows indicate phagocytosis events.

[0095] FIG. 82 shows fluorescent microscope images of in vitro phagocytosis of paclitaxel and gemcitabine treated Colo320 HSR colon cancer cells by CER13+ human primary B cells. Arrows indicate phagocytosis events.

[0096] FIG. 83 shows a vector map for a lentiviral vector comprising "CER15" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:79. CER15 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and truncated MyD88 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER15 sequence by a viral T2A sequence.

[0097] FIGS. 84A-B show FACS analysis of CER15+Ba/F3 effector cells (FIG. 84A) and quantification of engulfment of thymocytes by CER15+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 84B).

[0098] FIGS. 85A-B show fluorescent microscope images of in vitro phagocytosis of dexamethasone treated thymocytes by CER15+Ba/F3 cells (FIG. 85B) or control EGFRt+Ba/F3 cells (FIG. 85A). White arrows indicate phagocytosis events. High magnification of an engulfment event is shown on the right.

[0099] FIGS. 86A-B show phagocytic index for CER15+ cells or EGFRt+ control Ba/F3 cells. FIG. 86A shows a table of values for percentage of phagocytosing cells and hybrid capture values of CER15+ cells or EGFRt+ control Ba/F3 cells co-cultured with dexamethansone-treated thymocytes. FIG. 86B shows a graph of phagocytic index for CER15+ cells or EGFRt+ control Ba/F3 cells.

[0100] FIG. 87 shows a fluorescent microscope image of in vitro phagocytosis of staurosporine treated CT26 colon carcinoma cells by CER15+Ba/F3 cells. White arrows indicate phagocytosis events.

[0101] FIG. 88 shows a fluorescent microscope image of in vitro phagocytosis of staurosporine treated WR19L lymphoma cells by CER15+Ba/F3 cells. White arrows indicate phagocytosis events.

[0102] FIG. 89 shows a fluorescent microscope image of in vitro phagocytosis of staurosporine treated A20 lymphoma cells by CER15+Ba/F3 cells. White arrows indicate phagocytosis events.

[0103] FIGS. 90A-B show transduction and expansion of CER15+ human primary B cells. FIG. 90A shows FACS analysis of human primary B cells transduced with CER15 (right histogram) and control B cell (left histogram) using an anti-EGFR antibody and then an anti-Tim4 Kat5-18 antibody. FIG. 49B shows purified CER15+ B cells that were expanded at 24 hours, 48 hours and 72 hours.

[0104] FIG. 91 shows phagocytosis of staurosporine treated, pHrodo Red stained Jurkat cells by CER15+ human primary B cells as analyzed by FACS. Gating was performed on viable CD19+, allophycocyanin (APC)-labeled cells (left plot) and frequency of double positive stained events (APC and pHrodo Red) was defined as phagocytosis events (right plot).

[0105] FIG. 92 shows a graph of frequency of phagocytosis by CER15+ human primary B cells co-incubated with staurosporine treated Jurkat cells compared to control human primary B cells transduced with truncated EGFR.

[0106] FIGS. 93A-B show fluorescent microscope images of in vitro phagocytosis of staurosporine treated Jurkat cells by CER15+ human primary B cells (FIG. 93A) compared to control human primary B cells transduced with truncated EGFR (FIG. 93B). White arrows indicate phagocytosis events.

[0107] FIG. 94 shows a vector map for a lentiviral vector comprising "CER16" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:80. CER16 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and a MyD88 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER16 sequence by a viral T2A sequence.

[0108] FIG. 95 shows fluorescent microscope images of in vitro phagocytosis of Jurkat cells treated with oxaliplatin and fluorouracil by CER16+ human primary B cells. White arrows indicate phagocytosis events.

[0109] FIG. 96 shows a vector map for a lentiviral vector comprising "CER25" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:93. CER25 comprises a Tim4 binding domain, a Tim4 transmembrane domain, and a NFAM1 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER25 sequence by a viral T2A sequence.

[0110] FIGS. 97A-B show FACS quantification of engulfment of dexamethasone treated thymocytes by CER25+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 97B) compared to control Ba/F3 cells transduced with truncated EGFR (FIG. 97A).

[0111] FIG. 98 shows fluorescent microscope images of in vitro phagocytosis by CER25+Ba/F3 cells co-cultured with dexamethasone treated thymocytes. High magnification of an engulfment event is shown to the right. White arrows indicate phagocytosis events.

[0112] FIG. 99 shows a graph of phagocytic index of CER25+Ba/F3 cells co-cultured with dexamethasone treated thymocytes compared to Ba/F3 cells transduced with truncated EGFR.

[0113] FIG. 100 shows a vector map for a lentiviral vector comprising "CER85" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:95. CER85 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a truncated MyD88 signaling domain, and a secondary engulfment signaling domain that is a BAFFR signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER85 sequence by a viral T2A sequence.

[0114] FIGS. 101A-B show FACS quantification of engulfment of dexamethasone treated thymocytes by CER85+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 101A) compared to control Ba/F3 cells transduced with truncated EGFR (FIG. 101B).

[0115] FIG. 102 shows fluorescent microscope images of in vitro phagocytosis by CER85+Ba/F3 cells co-cultured with dexamethasone treated thymocytes. High magnification of an engulfment event is shown to the right. White arrows indicate phagocytosis events.

[0116] FIG. 103 shows a graph of phagocytic index of CER85+Ba/F3 cells co-cultured with dexamethasone treated thymocytes compared to control Ba/F3 cells transduced with truncated EGFR.

[0117] FIG. 104 shows a vector map for a lentiviral vector comprising "CER86" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:96. CER86 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a truncated MyD88 signaling domain, and a secondary engulfment signaling domain that is a DAP12 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER86 sequence by a viral T2A sequence.

[0118] FIG. 105 shows a vector map for a lentiviral vector comprising "CER8T" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 130. CER87 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a BAFFR signaling domain, and a secondary engulfment signaling domain that is a truncated MyD88 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER87 sequence by a viral T2A sequence.

[0119] FIGS. 106A-B show FACS quantification of engulfment of dexamethasone treated thymocytes by CER87+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 106A) compared to control Ba/F3 cells transduced with truncated EGFR (FIG. 106B).

[0120] FIG. 107 shows fluorescent microscope images of in vitro phagocytosis by CER87+Ba/F3 cells co-cultured with dexamethasone treated thymocytes. High magnification of an engulfment event is shown to the right. White arrows indicate phagocytosis events.

[0121] FIG. 108 shows a graph of phagocytic index of CER87+Ba/F3 cells co-cultured with dexamethasone treated thymocytes compared to control Ba/F3 cells transduced with truncated EGFR.

[0122] FIG. 109 shows a vector map for a lentiviral vector comprising "CER88" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 131. CER88 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a DAP12 signaling domain, and a secondary engulfment signaling domain that is a truncated MyD88 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER88 sequence by a viral T2A sequence.

[0123] FIG. 110 shows a vector map for a lentiviral vector comprising "CER89" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO:98. CER89 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a truncated MyD88 signaling domain, and a secondary engulfment signaling domain that is a CD79b signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER89 sequence by a viral T2A sequence.

[0124] FIG. 111 shows a vector map for a lentiviral vector comprising "CER90" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 100. CER90 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a truncated MyD88 signaling domain, and a secondary engulfment signaling domain that is a NFAM1 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER90 sequence by a viral T2A sequence.

[0125] FIG. 112 shows a vector map for a lentiviral vector comprising "CER91" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 105. CER91 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a truncated MyD88 signaling domain, a sequence encoding Rab5a, which is separated from the CER sequence by a viral P2A sequence, and a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the Rab5a sequence by a viral T2A sequence.

[0126] FIGS. 113A-B show FACS quantification of engulfment of dexamethasone treated thymocytes by CER91+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 113A) compared to control Ba/F3 cells transduced with truncated EGFR (FIG. 113B).

[0127] FIG. 114 shows fluorescent microscope images of in vitro phagocytosis by CER91+Ba/F3 cells co-cultured with dexamethasone treated thymocytes. High magnification of an engulfment event is shown to the right. White arrows indicate phagocytosis events.

[0128] FIG. 115 shows a graph of phagocytic index of CER91+Ba/F3 cells co-cultured with dexamethasone treated thymocytes compared to control Ba/F3 cells transduced with truncated EGFR.

[0129] FIG. 116 shows a vector map for a lentiviral vector comprising "CER92" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 133. CER92 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a MERTK signaling domain, and a secondary engulfment signaling domain that is a truncated MyD88 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO: 121), which is separated from the CER92 sequence by a viral T2A sequence.

[0130] FIGS. 117A-B show FACS quantification of engulfment of dexamethasone treated thymocytes by CER92+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 117A) compared to control Ba/F3 cells transduced with truncated EGFR (FIG. 117B).

[0131] FIG. 118 shows fluorescent microscope images of in vitro phagocytosis by CER92+Ba/F3 cells co-cultured with dexamethasone treated thymocytes. High magnification of an engulfment event is shown to the right. White arrows indicate phagocytosis events.

[0132] FIG. 119 shows a graph of phagocytic index of CER92+Ba/F3 cells co-cultured with dexamethasone treated thymocytes compared to control Ba/F3 cells transduced with truncated EGFR.

[0133] FIG. 120 shows a vector map for a lentiviral vector comprising "CER93" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 103. CER93 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a MERTK signaling domain, and a secondary engulfment signaling domain that is a BAFFR signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO:121), which is separated from the CER93 sequence by a viral T2A sequence.

[0134] FIGS. 121A-B show FACS quantification of engulfment of dexamethasone treated thymocytes by CER93+Ba/F3 murine B cells by measuring the cell population that stained double positive for pHrodo Red and CELLTRACE Violet (FIG. 121A) compared to control Ba/F3 cells transduced with truncated EGFR (FIG. 121B).

[0135] FIG. 122 shows fluorescent microscope images of in vitro phagocytosis by CER93+Ba/F3 cells co-cultured with dexamethasone treated thymocytes. High magnification of an engulfment event is shown to the right. White arrows indicate phagocytosis events.

[0136] FIG. 123 shows a graph of phagocytic index of CER93+Ba/F3 cells co-cultured with dexamethasone treated thymocytes compared to control Ba/F3 cells transduced with truncated EGFR.

[0137] FIG. 124 shows a vector map for a lentiviral vector comprising "CER94" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 134. CER94 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a MERTK signaling domain, and a secondary engulfment signaling domain that is a DAP12 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO:121), which is separated from the CER94 sequence by a viral T2A sequence.

[0138] FIG. 125 shows a vector map for a lentiviral vector comprising "CER9T" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 152. CER97 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is an Axl signaling domain, and a secondary engulfment signaling domain that is a DAP12 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO:121), which is separated from the CER97 sequence by a viral T2A sequence.

[0139] FIG. 126 shows a vector map for a lentiviral vector comprising "CER98" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 153. CER98 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is an Axl signaling domain, and a secondary engulfment signaling domain that is a CD79b signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO:121), which is separated from the CER98 sequence by a viral T2A sequence.

[0140] FIG. 127 shows a vector map for a lentiviral vector comprising "CER95" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 101. CER95 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a MERTK signaling domain, and a secondary engulfment signaling domain that is a CD79b signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO:121), which is separated from the CER95 sequence by a viral T2A sequence.

[0141] FIG. 128 shows a vector map for a lentiviral vector comprising "CER96" chimeric engulfment receptor having an amino acid sequence of SEQ ID NO: 102. CER96 comprises a Tim4 binding domain, a Tim4 transmembrane domain, a primary engulfment signaling domain that is a MERTK signaling domain, and a secondary engulfment signaling domain that is a NFAM1 signaling domain. The lentiviral vector also comprises a sequence encoding truncated EGFR (SEQ ID NO:121), which is separated from the CER96 sequence by a viral T2A sequence.

[0142] FIG. 129 shows phagocytic index of various CER+ Ba/F3 cells co-incubated with dexamethasone treated thymocytes as compared to control Ba/F3 cells transduced with truncated EGFRt.

[0143] FIG. 130 shows phagocytic index of various CER+ Ba/F3 cells co-incubated with staurosporine treated CT26 colon carcinoma cells as compared to control Ba/F3 cells transduced with truncated EGFRt.

[0144] FIG. 131 shows phagocytic index of various CER+ Ba/F3 cells co-incubated with staurosporine treated A20 lymphoma cells as compared to control Ba/F3 cells transduced with truncated EGFRt.

[0145] FIGS. 132A-C show in vivo synergy of CER0 (Tim4MerTk) 1 treatment with low dose radiation in a mouse model of lymphoma. FIG. 132A shows an exemplary timeline for a combination therapy regimen. FIG. 132B shows measurement of tumor size in untreated mice, mice receiving radiation+control T cells, or mice receiving radiation+CER01 modified T cells.

[0146] FIGS. 133A-B show in vivo synergy of CER01 (Tim4MerTk) treatment with chimeric antigen receptor (CAR) T cell therapy in a mouse model of lymphoma. FIG. 133A shows an exemplary timeline for a combination therapy regimen. FIG. 133B shows lucerifase imaging of tumor size in mice receiving anti-CD19 CAR modified T cells and CER modified B cells (n=3) or T cells (n=2) at day 4 post CER infusion (right image) as compared to control mice receiving anti-CD19 CAR modified T cells and pMSCV empty retroviral vector modified T cells (left photo).

[0147] FIG. 134 shows an illustrative triple combination treatment timeline comprising radiation therapy, CER immunotherapy (e.g., targeting phosphatidylserine expressing cells), followed by TCR or CAR immunotherapy.

DETAILED DESCRIPTION

[0148] Chimeric proteins including (a) an extracellular domain comprising an extracellular binding domain and, optionally, an extracellular spacer domain, (b) a transmembrane domain, and (c) an engulfment signaling domain, and nucleic acid molecules encoding said chimeric proteins are described herein. Additionally, cells modified to express these chimeric proteins and methods and compositions for delivery of such modified cells to a subject in need thereof are provided. The chimeric proteins are referred to herein as a "chimeric engulfment receptor" or "chimeric engulfment receptors" ("CER" in the singular and "CERs" in the plural). Chimeric engulfment receptors described herein are capable of conferring an engulfment phenotype to a host cell that is genetically modified to express said chimeric engulfment receptor. In such certain embodiments, expression of a CER as described herein confers an engulfment phenotype to a host cell that does not naturally exhibit an engulfment phenotype. In other such embodiments, expression of a CER as described herein by a host cell confers an engulfment phenotype specific to a pro-engulfment marker or antigenic marker not naturally targeted by the host cell. In still other such embodiments, expression of a CER as described herein by a host cell confers an engulfment phenotype specific to a pro-engulfment marker or antigenic marker naturally targeted by the host cell and expression of the CER by the host cell enhances engulfment by the host cell of cells, microbes, or particles exhibiting the targeted pro-engulfment or antigenic marker.

[0149] In certain embodiments, the CER targets an engulfment marker associated with apoptotic, dead, dying, damaged, infected, or necrotic cells. In other embodiments, the CER targets an antibody bound cell associated with an infectious microbe or particle. In still other embodiments, the CER targets an antigenic marker displayed by aberrant cells or misfolded proteins associated with a disease, disorder, or other undesired condition.

[0150] One or more CERs according to the present description can be transduced into and expressed in cells, such as T cells, Natural Killer Cells, Natural Killer T cells, B cells, lymphoid precursor cells, dendritic cells, Langerhans cells, and myeloid cells. In certain embodiments, in addition to engineering the CER to bind to a specified target molecule (e.g., an engulfment marker or an antigenic marker), the engulfment signaling domain of the CER is selected to provide desired engulfment activity. In one such embodiment, the engulfment signaling domain is selected to induce homeostatic engulfment signaling. In another such embodiment, the engulfment signaling domain is selected to induce pro-inflammatory engulfment signaling. In yet another embodiment, the engulfment signaling domain comprises a primary engulfment signaling domain and a secondary engulfment signaling domain. The primary engulfment signaling domain and the secondary engulfment signaling domain may both be homeostatic engulfment signaling domains, both be pro-inflammatory engulfment signaling domains, or the primary engulfment signaling domain may be a homeostatic engulfment signaling domain and the secondary engulfment signaling domain may be a pro-inflammatory engulfment signaling domain (or vice versa).

[0151] Host cells that are genetically modified to express one or more CERs according to the present description can be used for specific engulfment of a target cell or particle expressing a target molecule to which the extracellular domain of the CER binds. In certain embodiments, the target cell or particle may be a tumor cell, a cancer cell, a microbe (e.g., bacteria, fungus, virus), a protozoan parasite, an aberrant cell, or a misfolded protein associated with an infection, disease, disorder, or other undesired condition. In further embodiments, host cells that are genetically modified to express one or more CERs according to the present description are used to treat cancer, an infectious disease (viral, bacterial, fungal, protozoan), an inflammatory disease, an immune disease (e.g., autoimmune disease), or a neurodegenerative disease (e.g., Alzheimer's disease) in a subject, either as a primary therapy or as an adjunct or combination therapy. The CER of the present disclosure can be designed to confer a specific engulfment phenotype (e.g., homeostatic (non-immunogenic) vs. pro-inflammatory (immunogenic)) via selection of a homeostatic engulfment signaling domain or pro-inflammatory engulfment signaling domain, depending upon on the target molecule and therapeutic indication. Without wishing to be bound by theory, a CER comprising a proinflammatory engulfment domain may be useful in improving the microenvironment of cancers and enhancing tumor regression.

Definitions

[0152] Prior to setting forth this disclosure in more detail, it may be helpful to an understanding thereof to provide definitions of certain terms to be used herein.

[0153] In the present description, any concentration range, percentage range, ratio range, or integer range is to be understood to include the value of any integer within the recited range and, when appropriate, fractions thereof (such as one tenth and one hundredth of an integer), unless otherwise indicated. Also, any number range recited herein relating to any physical feature, such as polymer subunits, size or thickness, are to be understood to include any integer within the recited range, unless otherwise indicated. As used herein, the term "about" means.+-.20% of the indicated range, value, or structure, unless otherwise indicated. It should be understood that the terms "a" and "an" as used herein refer to "one or more" of the enumerated components. The use of the alternative (e.g., "or") should be understood to mean either one, both, or any combination thereof of the alternatives. As used herein, the terms "include," "have" and "comprise" are used synonymously, which terms and variants thereof are intended to be construed as non-limiting.

[0154] Terms understood by those in the art of antibody technology are each given the meaning acquired in the art, unless expressly defined differently herein. The term "antibody" is used in the broadest sense and includes polyclonal and monoclonal antibodies. An "antibody" may refer to an intact antibody comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds, as well as an antigen-binding portion (or antigen-binding domain) of an intact antibody that has or retains the capacity to bind a target molecule. An antibody may be naturally occurring, recombinantly produced, genetically engineered, or modified forms of immunoglobulins, for example intrabodies, peptibodies, nanobodies, single domain antibodies, SMIPs, multispecific antibodies (e.g., bispecific antibodies, diabodies, triabodies, tetrabodies, tandem di-scFV, tandem tri-scFv, ADAPTIR). A monoclonal antibody or antigen-binding portion thereof may be non-human, chimeric, humanized, or human, preferably humanized or human. Immunoglobulin structure and function are reviewed, for example, in Harlow et al., Eds., Antibodies: A Laboratory Manual, Chapter 14 (Cold Spring Harbor Laboratory, Cold Spring Harbor, 1988). "Antigen-binding portion" or "antigen-binding domain" of an intact antibody is meant to encompass an "antibody fragment," which indicates a portion of an intact antibody and refers to the antigenic determining variable regions or complementary determining regions of an intact antibody. Examples of antibody fragments include, but are not limited to, Fab, Fab', F(ab')2, and Fv fragments, Fab'-SH, F(ab').sub.2, diabodies, linear antibodies, scFv antibodies, VH, and multispecific antibodies formed from antibody fragments. A "Fab" (fragment antigen binding) is a portion of an antibody that binds to antigens and includes the variable region and CH1 of the heavy chain linked to the light chain via an inter-chain disulfide bond. An antibody may be of any class or subclass, including IgG and subclasses thereof (IgG.sub.1, IgG.sub.2, IgG.sub.3, IgG.sub.4), IgM, IgE, IgA, and IgD.

[0155] The term "variable region" or "variable domain" refers to the domain of an antibody heavy or light chain that is involved in binding of the antibody to antigen. The variable domains of the heavy chain and light chain (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved framework regions (FRs) and three CDRs. (See, e.g., Kindt et al. Kuby Immunology, 6th ed., W.H. Freeman and Co., page 91 (2007). A single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind a particular antigen may be isolated using a VH or VL domain from an antibody that binds the antigen to screen a library of complementary VL or VH domains, respectively. See, e.g., Portolano et al., J. Immunol. 150:880-887 (1993); Clarkson et al., Nature 352:624-628 (1991).

[0156] The terms "complementarity determining region" and "CDR," which are synonymous with "hypervariable region" or "HVR," are known in the art to refer to non-contiguous sequences of amino acids within antibody variable regions, which confer antigen specificity and/or binding affinity. In general, there are three CDRs in each heavy chain variable region (HCDR1, HCDR2, HCDR3) and three CDRs in each light chain variable region (LCDR1, LCDR2, LCDR3).

[0157] The terms "antigen" and "Ag" refer to a molecule that provokes an immune response. The immune response provoked may involve antibody production, the activation of specific immunologically-competent cells, or both. Macromolecules, including proteins, glycoproteins, and glycolipids, can serve as an antigen. Antigens can be derived from recombinant or genomic DNA. As contemplated herein, an antigen need not be encoded (i) solely by a full length nucleotide sequence of a gene or (ii) by a "gene" at all. An antigen can be generated or synthesized, or an antigen can be derived from a biological sample. Such a biological sample can include, but is not limited, to a tissue sample, a tumor sample, a cell, or a biological fluid.

[0158] The term "epitope" or "antigenic epitope" includes any molecule, structure, amino acid sequence or protein determinant within an antigen that is specifically bound by a cognate immune binding molecule, such as an antibody or fragment thereof (e.g., scFv), T cell receptor (TCR), chimeric engulfment receptor, or other binding molecule, domain or protein. Epitopic determinants generally contain chemically active surface groupings of molecules, such as amino acids or sugar side chains, and can have specific three dimensional structural characteristics, as well as specific charge characteristics. An epitope may be a linear epitope or a conformational epitope.

[0159] The term "anti-tumor effect" refers to a biological effect which can be manifested by a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in the number of metastases, an increase in life expectancy, or amelioration of various physiological symptoms associated with a cancerous condition. An "anti-tumor effect" can also be manifested by prevention of a hematological malignancy or tumor formation.

[0160] "Autoimmune disease" refers to a disorder that results from an autoimmune response. An autoimmune disease is the result of an inappropriately excessive response to a self-antigen. An autoimmune response may involve self-reactive B-cells that produce autoantibodies, self-reactive T-cells, or both. An "autoantibody" as used herein is an antibody produced by a subject that binds to a self-antigen also produced by the subject.

[0161] "Autologous" refers to any material derived from the same subject to which it is later to be re-introduced.

[0162] "Allogeneic" refers to a graft derived from a different subject of the same species.

[0163] As used herein, the terms "binding domain," "binding region," and "binding moiety" refer to a molecule, such as a peptide, oligopeptide, polypeptide, or protein that possesses the ability to specifically and non-covalently bind, associate, unite, recognize, or combine with a target molecule (e.g., PtdSer, an IgG antibody, an IgE antibody, an IgA antibody, CD138, CD38, CD33, CD123, CD79b, mesothelin, PSMA, BCMA, ROR1, MUC-16, L1CAM, CD22, CD19, EGFRviii, VEGFR-2, or GD2). A binding domain includes any naturally occurring, synthetic, semi-synthetic, or recombinantly produced binding partner for a biological molecule or other target of interest. In some embodiments, the binding domain is an antigen-binding domain, such as an antibody or functional binding domain or antigen-binding portion thereof. Exemplary binding domains include single chain antibody variable regions (e.g., domain antibodies, sFv, scFv, Fab), receptor ectodomains (e.g., TNF-.alpha.), ligands (e.g., cytokines, chemokines), or synthetic polypeptides selected for the specific ability to bind to a biological molecule.

[0164] A variety of assays are known for identifying binding domains of the present disclosure that specifically bind a particular target, as well as determining binding domain affinities, such as Western blot, ELISA, and BIACORE.RTM. analysis (see also, e.g., Scatchard et al., Ann. N.Y. Acad. Sci. 51:660, 1949; and U.S. Pat. Nos. 5,283,173, 5,468,614, or the equivalent). As used herein, "specifically binds" refers to an association or union of a binding domain, or a fusion protein thereof, to a target molecule with an affinity or K.sub.a (i.e., an equilibrium association constant of a particular binding interaction with units of 1/M) equal to or greater than 10.sup.5 M.sup.-1, while not significantly associating or uniting with any other molecules or components in a sample.

[0165] The term "cancer" as used herein is defined as disease characterized by the rapid and uncontrolled growth of aberrant cells. The aberrant cells may form solid tumors or constitute a hematological malignancy. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body. Examples of various cancers include, but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, lymphoma, leukemia, lung cancer and the like.

[0166] A "disease" is a state of health of a subject wherein the subject cannot maintain homeostasis, and wherein, if the disease is not ameliorated, then the subject's health continues to deteriorate. In contrast, a "disorder" or "undesirable condition" in a subject is a state of health in which the subject is able to maintain homeostasis, but in which the subject's state of health is less favorable than it would be in the absence of the disorder or undesirable condition. Left untreated, a disorder or undesirable condition does not necessarily result in a further decrease in the subject's state of health.

[0167] A "microbe" or "microorganism" refers to any species of bacteria, virus, archaea, or fungi.

[0168] A "particle" refers to a fragment of a cell or a small object of at least 100 nm and up to 6 .mu.m in diameter and that is derived from a living cell or organism. A particle can be a viral particle, small mineral particle, cellular debris, or a synthetic particle.

[0169] "Encoding" refers to the inherent property of specific polynucleotide sequences, such as DNA, cDNA, and mRNA sequences, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (i.e., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom.

[0170] Thus, a polynucleotide encodes a protein if transcription and translation of mRNA corresponding to that polynucleotide produces the protein in a cell or other biological system. Both a coding strand and a non-coding strand can be referred to as encoding a protein or other product of the polynucleotide.

[0171] Unless otherwise specified, a "nucleotide sequence encoding an amino acid sequence" includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence.

[0172] As used herein, the term "endogenous" or "native" refers to a gene, protein, compound, molecule or activity that is normally present in a host or host cell.

[0173] As used herein, the term "engulfment" refers to a receptor-mediated process wherein endogenous or exogenous cells or particles greater than 100 nm in diameter are internalized by a phagocyte or host cell of the present disclosure. Engulfment is typically composed of multiple steps: (1) tethering of the target cell or particle via binding of an engulfment receptor to a pro-engulfment marker or antigenic marker directly or indirectly (via a bridging molecule) on a target cell or particle; and (2) internalization or engulfment of the whole target cell or particle, or a portion thereof. In certain embodiments, internalization may occur via cytoskeletal rearrangement of a phagocyte or host cell to form a phagosome, a membrane-bound compartment containing the internalized target. Engulfment may further include maturation of the phagosome, wherein the phagosome becomes increasingly acidic and fuses with lysosomes (to form a phagolysosome), whereupon the engulfed target is degraded (e.g., "phagocytosis"). Alternatively, phagosome-lysosome fusion may not be observed in engulfment. In yet another embodiment, a phagosome may regurgitate or discharge its contents to the extracellular environment before complete degradation. In some embodiments, engulfment refers to phagocytosis. In some embodiments, engulfment includes tethering of the target cell or particle by the phagocyte of host cell of the present disclosure, but not internalization. In some embodiments, engulfment includes tethering of the target cell or particle by the phagocyte of host cell of the present disclosure and internalization of part of the target cell or particle.

[0174] As used herein, the term "phagocytosis" refers to an engulfment process of cells or large particles (.gtoreq.0.5 .mu.m) wherein tethering of a target cell or particle, engulfment of the target cell or particle, and degradation of the internalized target cell or particle occurs. In certain embodiments, phagocytosis comprises formation of a phagosome that encompasses the internalized target cell or particle and phagosome fusion with a lysosome to form a phagolysosome, wherein the contents therein are degraded. In certain embodiments, during phagocytosis, following binding of a CER expressed on a phagocyte or a host cell of the present disclosure to an engulfment marker expressed by a target cell or particle, a phagocytic synapse is formed; an actin-rich phagocytic cup is generated at the phagocytic synapse; phagocytic arms are extended around the target cell or particle through cytoskeletal rearrangements; and ultimately, the target cell or particle is pulled into the phagocyte or host cell through force generated by motor proteins. As used herein, "phagocytosis" includes the process of"efferocytosis", which specifically refers to the phagocytosis of apoptotic or necrotic cells in a non-inflammatory manner.

[0175] As used herein, the term "pro-engulfment marker" refers to a moiety (e.g., protein, lipid, or polysaccharide) that an apoptotic, necrotic, pyroptotic, or infected cell exhibits on its surface that distinguishes it from a non-apoptotic, non-necrotic, non-pyroptotic, oncotic, or uninfected cell, respectively. A pro-engulfment marker can be an intracellular moiety that is surface exposed on an apoptotic or necrotic cell, a moiety that has altered glycosylation or altered surface charge on an apoptotic or necrotic cell, or a serum moiety that is bound to an apoptotic, necrotic, pyroptotic, or oncotic cell. Examples of pro-engulfment markers for apoptotic cells include phosphatidylserine (PtdSer), ICAM-3, oxidized low density lipoprotein, calreticulin, annexin I, complement C1q, and thrombospondin. Necrotic, oncotic, and pyroptotic cells also expose PtdSer pro-engulfment markers on the cell surface. Engulfment receptors can detect (or bind) a pro-engulfment marker on a target cell (e.g., a damaged, infected, apoptotic, necrotic, pyroptotic, or oncotic cell) directly or indirectly using soluble bridging molecules as intermediaries that bind to the pro-engulfment marker.

[0176] An "engulfment signaling domain" refers to an intracellular effector domain, which, upon binding of the target molecule (e.g., pro-engulfment marker or antigenic marker) targeted by the extracellular domain of a CER expressed by a host cell, activates one or more signaling pathways in the host cell resulting in engulfment, including, in specific embodiments, cytoskeletal rearrangement of the host cell and internalization of the target cell, microbe, or particle associated with the marker or antigen. In certain embodiments, an engulfment signaling domain activates one or more signaling pathways resulting in phagocytosis of the target cell, microbe, or particle. In certain embodiments, the engulfment signaling domain includes a primary engulfment signaling domain. In certain other embodiments, the engulfment signaling domain includes a primary engulfment signaling domain and a secondary engulfment signaling domain. A primary engulfment may be a homeostatic engulfment signaling domain or a pro-inflammatory engulfment signaling domain. In embodiments where the engulfment signaling domain includes a primary engulfment signaling domain and a secondary engulfment signaling domain, the primary engulfment signaling domain can be a homeostatic engulfment signaling domain or a pro-inflammatory engulfment signaling domain. Similarly, the secondary engulfment signaling domain can be selected from a homeostatic engulfment signaling domain or a pro-inflammatory engulfment signaling domain. In certain embodiments, the CER includes a primary engulfment signaling domain and a secondary engulfment signaling domain that are both homeostatic engulfment signaling domains. In certain other embodiments, the CER includes a primary engulfment signaling domain and a secondary engulfment signaling domain that are both pro-inflammatory engulfment signaling domains. In still other embodiments, the CER includes a primary engulfment signaling domain that is a homeostatic engulfment signaling domain and a secondary engulfment signaling domain that is a pro-inflammatory engulfment signaling domain. In still other embodiments, the CER includes a primary engulfment signaling domain that is a pro-inflammatory engulfment signaling domain and a secondary engulfment signaling domain that is a homeostatic engulfment signaling domain.

[0177] The term "homeostatic engulfment signaling domain" refers to an effector domain that (i) stimulates engulfment of the targeted cell, microbe, or particle without (ii) is derived from an endogenous receptor or signaling molecule that typically stimulates an inflammatory or immunogenic response. In some embodiments, a homeostatic engulfment signaling domain stimulates host cell secretion of anti-inflammatory and/or immunosuppressive cytokines, such as, for example, TGF-3 and IL-10. In certain embodiments, stimulation of homeostatic engulfment signaling dampens, attenuates, or resolves inflammation in the local tissue milieu. A homeostatic engulfment signaling domain can also be referred to as a "non-inflammatory" engulfment signaling domain or a "non-immunogenic" engulfment signaling domain.

[0178] A "pro-inflammatory engulfment signaling domain" refers to an effector domain that (i) stimulates engulfment of the targeted cell, microbe, or particle and (ii) is derived from an endogenous receptor or signaling molecule that typically stimulates one or more of (a) host cell secretion of inflammatory cytokines, such as, for example, TNF.alpha., IL-1, IL-6, IL-12, and IL-23, (b) host cell secretion of inflammatory chemokines, such as, for example, CCL5 (RANTES), CXCL9, and CXCL10, (c) upregulation of cell surface co-stimulatory markers, such as, for example, CD80, CD86, HLA-DR, CD40, HVEM, and 4-1BBL, and (d) activation of one or more signaling cascades, such as NF-.kappa.B, that induce, potentiate, or complement chemotherapies, antibody-based immune therapies, or cellular therapies, such as, for example, T cell targeted therapies. In certain embodiments, stimulation of pro-inflammatory engulfment signaling promotes inflammation in the local tissue milieu. A pro-inflammatory engulfment signaling domain can also be referred to as an "immunogenic" engulfment signaling domain or an "inflammatory" engulfment signaling domain.

[0179] As used herein, an "effector domain" is an intracellular portion of a fusion protein or receptor that can directly or indirectly promote a biological or physiological response in a cell expressing the effector domain when receiving the appropriate signal. In certain embodiments, an effector domain is part of a protein or protein complex that receives a signal when bound, or it binds directly to a target molecule, which triggers a signal from the effector domain. For example, in response to binding of the CER to a target molecule, the effector domain may transduce a signal to the interior of the host cell, eliciting an effector function, e.g., engulfment, phagolysosome maturation, secretion of anti-inflammatory and/or immunosuppressive cytokines, secretion of inflammatory cytokines and/or chemokines. An effector domain may directly promote a cellular response when it contains one or more signaling domains or motifs. In other embodiments, an effector domain will indirectly promote a cellular response by associating with one or more other proteins that directly promote a cellular response.

[0180] As used herein, "heterologous" or "non-endogenous" or "exogenous" refers to any gene, protein, compound, molecule, or activity that is not native to a host cell or a subject, or is any gene, protein, compound, molecule, or activity native to a host or host cell but has been altered or mutated such that the structure, activity, or both is different as between the native and mutated molecules. In certain embodiments, heterologous, non-endogenous or exogenous molecules (e.g., receptors, ligands) may not be endogenous to a host cell or subject, but instead nucleic acids encoding such molecules may have been added to a host cell by conjugation, transformation, transfection, electroporation, or the like, wherein the added nucleic acid molecule may integrate into a host cell genome or can exist as extra-chromosomal genetic material (e.g., as a plasmid or other self-replicating vector). The term "homologous" or "homolog" refers to a molecule or activity found in or derived from a host cell, species or strain. For example, a heterologous or exogenous molecule or gene encoding the molecule may be homologous to a native host or host cell molecule or gene that encodes the molecule, respectively, but may have an altered structure, sequence, expression level, or combinations thereof. A non-endogenous molecule may be from the same species, a different species or a combination thereof.

[0181] "Junction amino acids" or "junction amino acid residues" refer to one or more (e.g., about 2-20) amino acid residues between two adjacent motifs, regions or domains of a polypeptide. Junction amino acids may result from the construct design of a chimeric protein (e.g., amino acid residues resulting from the use of a restriction enzyme site during the construction of a nucleic acid molecule encoding a fusion protein).

[0182] "Nucleic acid molecule" and "polynucleotide" can be in the form of RNA or DNA, which includes cDNA, genomic DNA, and synthetic DNA. A nucleic acid molecule may be double stranded or single stranded, and if single stranded, may be the coding strand or non-coding (anti-sense strand). A coding molecule may have a coding sequence identical to a coding sequence known in the art or may have a different coding sequence, which, as the result of the redundancy or degeneracy of the genetic code, or by splicing, can encode the same polypeptide.

[0183] The term "overexpressed" or "overexpression" of an antigen refers to an abnormally high level of antigen expression in a cell. Overexpressed antigen or overexpression of antigen is often associated with a disease state, such as in hematological malignancies and cells forming a solid tumor within a specific tissue or organ of a subject. Solid tumors or hematological malignancies characterized by overexpression of a tumor antigen can be determined by standard assays known in the art.

[0184] As used herein, the terms "peptide," "polypeptide," and "protein" are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein's or peptide's sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. "Polypeptides" include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. The polypeptides include natural peptides, recombinant peptides, synthetic peptides, or a combination thereof.

[0185] As used herein, the term "mature polypeptide" or "mature protein" refers to a protein or polypeptide that is secreted or localized in the cell membrane or inside certain cell organelles (e.g., the endoplasmic reticulum, golgi, or endosome) and does not include an N-terminal signal peptide.

[0186] A "signal peptide", also referred to as "signal sequence", "leader sequence", "leader peptide", "localization signal" or "localization sequence", is a short peptide (usually 15-30 amino acids in length) present at the N-terminus of newly synthesized proteins that are destined for the secretory pathway. A signal peptide typically comprises a short stretch of hydrophilic, positively charged amino acids at the N-terminus, a central hydrophobic domain of 5-15 residues, and a C-terminal region with a cleavage site for a signal peptidase. In eukaryotes, a signal peptide prompts translocation of the newly synthesized protein to the endoplasmic reticulum where it is cleaved by the signal peptidase, creating a mature protein that then proceeds to its appropriate destination.

[0187] The "percent identity" between two or more nucleic acid or amino acid sequences is a function of the number of identical positions shared by the sequences (i.e., % identity=number of identical positions/total number of positions.times.100), taking into account the number of gaps, and the length of each gap that needs to be introduced to optimize alignment of two or more sequences. The comparison of sequences and determination of percent identity between two or more sequences can be accomplished using a mathematical algorithm, such as BLAST and Gapped BLAST programs at their default parameters (e.g., Altschul et al., J. Mol. Biol. 215:403, 1990; see also BLASTN at www.ncbi.nlm.nih.gov/BLAST).

[0188] A "conservative substitution" is recognized in the art as a substitution of one amino acid for another amino acid that has similar properties. Exemplary conservative substitutions are well known in the art (see, e.g., WO 97/09433, page 10, published Mar. 13, 1997; Lehninger, Biochemistry, Second Edition; Worth Publishers, Inc. NY:NY (1975), pp. 71-77; Lewin, Genes IV, Oxford University Press, NY and Cell Press, Cambridge, Mass. (1990), p. 8).

[0189] The term "chimeric" refers to any nucleic acid molecule or protein that is not endogenous and comprises sequences joined or linked together that are not normally found joined or linked together in nature. For example, a chimeric nucleic acid molecule may comprise regulatory sequences and coding sequences that are derived from different sources, or regulatory sequences and coding sequences that are derived from the same source but arranged in a manner different than that found in nature.

[0190] The term "promoter" as used herein is defined as a DNA sequence recognized by the synthetic machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence.

[0191] As used herein, the term "promoter/regulatory sequence" means a nucleic acid sequence which is required for expression of a gene product operably linked to the promoter/regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements which are required for expression of the gene product. The promoter/regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner.

[0192] A "constitutive" promoter is a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell under most or all physiological conditions of the cell.

[0193] An "inducible" promoter is a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell substantially only when an inducer which corresponds to the promoter is present in the cell.

[0194] A "tissue-specific" promoter is a nucleotide sequence which, when operably linked with a polynucleotide encodes or specified by a gene, causes the gene product to be produced in a cell substantially only if the cell is a cell of the tissue type corresponding to the promoter.

[0195] The term "subject," "patient" and "individual" are used interchangeably herein and are intended to include living organisms in which an immune response can be elicited (e.g., mammals). Examples of subjects include humans, primates, cows, horses, sheep, dogs, cats, mice, rats, rabbits, guinea pigs, pigs, and transgenic species thereof

[0196] The term "T cells" refers to cells of T cell lineage. "Cells of T cell lineage" refers to cells that show at least one phenotypic characteristic of a T cell or a precursor or progenitor thereof that distinguishes the cells from other lymphoid cells, and cells of the erythroid or myeloid lineages. Such phenotypic characteristics can include expression of one or more proteins specific for T cells (e.g., CD3.sup.+, CD4.sup.+, CD8.sup.+), or a physiological, morphological, functional, or immunological feature specific for a T cell. For example, cells of the T cell lineage may be progenitor or precursor cells committed to the T cell lineage; CD25.sup.+ immature and inactivated T cells; cells that have undergone CD4 or CD8 linage commitment; thymocyte progenitor cells that are CD4.sup.+CD8.sup.+ double positive; single positive CD4.sup.+ or CD8.sup.+; TCR.alpha..beta. or TCR .gamma..delta.; or mature and functional or activated T cells. The term "T cells" encompasses naive T cells (CD45 RA+, CCR7+, CD62L+, CD27+, CD45RO-), central memory T cells (CD45RO.sup.+, CD62L.sup.+, CD8.sup.+), effector memory T cells (CD45RA+, CD45RO-, CCR7-, CD62L-, CD27-), mucosal-associated invariant T cells, natural killer T cells, and tissue resident T cells.

[0197] The term "B cells" refers to cells of the B cell lineage. "Cells of B cell lineage" refers to cells that show at least one phenotypic characteristic of a B cell or a precursor or progenitor thereof that distinguishes the cells from other lymphoid cells, and cells of the erythroid or myeloid lineages. Such phenotypic characteristics can include expression of one or more proteins specific for B cells (e.g., CD19.sup.+, CD72+, CD24+, CD20+), or a physiological, morphological, functional, or immunological feature specific for a B cell. For example, cells of the B cell lineage may be progenitor or precursor cells committed to the B cell lineage (e.g., pre-pro-B cells, pro-B cells, and pre-B cells); immature and inactivated B cells or mature and functional or activated B cells. Thus, "B cells" encompass naive B cells, plasma cells, regulatory B cells, marginal zone B cells, follicular B cells, lymphoplasmacytoid cells, plasmablast cells, and memory B cells (e.g., CD27.sup.+, IgD.sup.-).

[0198] A "therapeutically effective amount" or "effective amount" of a chimeric protein or cell expressing a chimeric protein of this disclosure (e.g., a CER or a cell expressing a CER) refers to that amount of protein or cells sufficient to result in amelioration of one or more symptoms of the disease, disorder, or undesired condition being treated. When referring to an individual active ingredient or a cell expressing a single active ingredient, administered alone, a therapeutically effective dose refers to the effects of that ingredient or cell expressing that ingredient alone. When referring to a combination, a therapeutically effective dose refers to the combined amounts of active ingredients or combined adjunctive active ingredient with a cell expressing an active ingredient that results in a therapeutic effect, whether administered serially or simultaneously.

[0199] "Treat" or "treatment" or "ameliorate" refers to medical management of a disease, disorder, or undesired condition of a subject. In general, an appropriate dose or treatment regimen comprising a host cell expressing a CER of this disclosure is administered in an amount sufficient to elicit a therapeutic or prophylactic benefit. Therapeutic or prophylactic/preventive benefit includes improved clinical outcome; lessening or alleviation of symptoms associated with a disease, disorder, or undesired condition; decreased occurrence of symptoms; improved quality of life; longer disease-free status; diminishment of extent of disease, disorder, or undesired condition; stabilization of disease state; delay of disease progression; remission; survival; prolonged survival; or any combination thereof.

[0200] The phrase "under transcriptional control" or "operatively linked" as used herein means that a promoter is in the correct location and orientation in relation to a polynucleotide to control the initiation of transcription by RNA polymerase and expression of the polynucleotide.

[0201] A "vector" is a nucleic acid molecule that is capable of transporting another nucleic acid. Vectors may be, for example, plasmids, cosmids, viruses, or phage. The term should also be construed to include non-plasmid and non-viral compounds which facilitate transfer of nucleic acid into cells. An "expression vector" is a vector that is capable of directing the expression of a protein encoded by one or more genes carried by the vector when it is present in the appropriate environment.

[0202] In certain embodiments, the vector is a viral vector. Examples of viral vectors include, but are not limited to, adenovirus vectors, adeno-associated virus vectors, retrovirus vectors, gammaretrovirus vectors, and lentivirus vectors. "Retroviruses" are viruses having an RNA genome. "Gammaretrovirus" refers to a genus of the retroviridae family. Examples of gammaretroviruses include mouse stem cell virus, murine leukemia virus, feline leukemia virus, feline sarcoma virus, and avian reticuloendotheliosis viruses. "Lentivirus" refers to a genus of retroviruses that are capable of infecting dividing and non-dividing cells. Examples of lentiviruses include, but are not limited to HIV (human immunodeficiency virus, including HIV type 1 and HIV type 2, equine infectious anemia virus, feline immunodeficiency virus (FIV), bovine immune deficiency virus (BIV), and simian immunodeficiency virus (SIV).

[0203] In other embodiments, the vector is a non-viral vector. Examples of non-viral vectors include lipid-based DNA vectors, modified mRNA (modRNA), self-amplifying mRNA, closed-ended linear duplex (CELiD) DNA, and transposon-mediated gene transfer (PiggyBac, Sleeping Beauty). Where a non-viral delivery system is used, the delivery vehicle can be a liposome. Lipid formulations can be used to introduce nucleic acids into a host cell in vitro, ex vivo, or in vivo. The nucleic acid may be encapsulated in the interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the nucleic acid, contained or complexed with a micelle, or otherwise associated with a lipid.

[0204] Additional definitions are provided throughout the present disclosure.

Chimeric Engulfment Receptors (CERs)

[0205] Chimeric engulfment receptors (CERs) are described herein. In particular embodiments, the CER is a chimeric, single chain protein, which comprises an extracellular domain and an engulfment signaling domain, which are connected by a transmembrane domain. The extracellular domain includes an extracellular binding domain and, optionally, an extracellular spacer domain. When expressed in a host cell, a CER confers an engulfment phenotype to the modified host cell (the host cell is "switched" to an engulfment phenotype) specific to a selected pro-engulfment marker or antigenic marker present on or expressed by target cells, microbes, particles, or other materials. In certain embodiments, a CER confers a phagocytic phenotype to the modified host cell specific to a selected pro-engulfment marker or antigenic marker present on or expressed by target cells, microbes, particles, or other materials. In particular CER embodiments, the chimeric protein comprises, from amino-terminus to carboxyl-terminus: an extracellular domain having a binding domain specific for a target molecule and an optional extracellular spacer domain; a transmembrane domain; and an engulfment signaling domain (see, e.g., FIGS. 1A and 1B).

[0206] The component parts of a CER as disclosed herein can be selected and arranged to provide a desired engulfment phenotype. For example, in certain embodiments, the extracellular domain can include a binding domain specific to: (i) a pro-engulfment marker associated with apoptotic, dead, dying, damaged, or necrotic cells; or (ii) an antigenic marker displayed by foreign (e.g., a microbe), infected, or aberrant cells associated with an infection, disease, disorder, or other undesired condition.

[0207] The engulfment signaling domain can include one or more effector (also referred to as "signaling") domains that drive engulfment of the targeted cell. Signaling by the engulfment signaling domain is triggered by binding of the extracellular domain to the targeted pro-engulfment or antigenic marker. In certain embodiments, the engulfment signaling domain comprises a primary engulfment signaling domain. In particular embodiments, the primary engulfment signaling domain is selected to initiate a homeostatic engulfment response. Alternatively, in other embodiments, the primary engulfment signaling domain is selected to initiate a pro-inflammatory engulfment response. In yet other embodiments, the engulfment signaling domain comprises a primary engulfment signaling domain and a secondary engulfment signaling domain, wherein the primary and secondary engulfment signaling domains are both homeostatic signaling domains, both pro-inflammatory signaling domains, or one of each (in any order). A CER according to the present disclosure can be engineered for application in a variety of therapeutic contexts (e.g., clearance of apoptotic, dead, dying, damaged, infected, or necrotic cells, clearance of microbes responsible for infectious disease, and clearance of aberrant cells associated with a disease, disorder or undesired condition), while providing engulfment signaling that complements the desired therapeutic outcome (e.g., homeostatic or pro-inflammatory engulfment signaling).

[0208] FIGS. 3A and 3B provide a functional comparison of a natural lymphocyte with a lymphocyte modified with an embodiment of a CER of the present disclosure. FIG. 3A shows an endogenous lymphocyte, and as is represented in the figure, the natural lymphocyte does not exhibit an engulfment phenotype. However, as is illustrated in FIG. 3B, a lymphocyte modified to express a CER as described herein exhibits an engulfment phenotype specific to the targeted cancer cell, leading to engulfment (e.g., phagocytosis) and elimination of the targeted cancer cell. Even further, as is illustrated in FIG. 3B, in certain embodiments the CER can be engineered to drive polarization of the engulfment process. In particular embodiments, the engulfment signaling domains included in CERs according to the present description can be selected to drive homeostatic engulfment signaling or pro-inflammatory engulfment signaling.

[0209] Component parts of the fusion proteins of the present disclosure are further described in detail herein.

Extracellular Domain

[0210] As described herein, a CER comprises an extracellular domain specific to a target molecule. In certain embodiments, the extracellular domain includes an extracellular binding domain that specifically binds a targeted pro-engulfment marker or antigen. Binding of a target molecule by the binding domain may block the interaction between the target molecule (e.g., a receptor or a ligand) and another molecule and, for example, interfere with, reduce or eliminate certain functions of the target molecule (e.g., signal transduction). In some embodiments, the binding of a target molecule may induce certain biological pathways or identify the target molecule or cell expressing the target molecule for elimination.

[0211] A binding domain may be any polypeptide or peptide that specifically binds a target molecule of interest. Sources of binding domains include receptor binding domains, ligand binding domains, and antibodies or antigen binding portions, such as antibody variable regions from various species (which can be in the form of antibodies, sFvs, scFvs, Fabs, scFv-based grababody, or soluble VH domain or domain antibodies), including human, rodent, avian, or ovine. Additional sources of binding domains include variable regions of antibodies from other species, such as camelid (from camels, dromedaries, or llamas; Ghahroudi et al., FEBS Lett. 414:521, 1997; Vincke et al., J. Biol. Chem. 284:3273, 2009; Hamers-Casterman et al., Nature 363:446, 1993 and Nguyen et al., J. Mol. Biol. 275:413, 1998), nurse sharks (Roux et al., Proc. Nat'l. Acad. Sci. (USA) 95:11804, 1998), spotted ratfish (Nguyen et al., Immunogen. 54:39, 2002), or lamprey (Herrin et al., Proc. Nat'l. Acad. Sci. (USA) 105:2040, 2008 and Alder et al. Nat. Immunol. 9:319, 2008). These antibodies can form antigen-binding regions using only a heavy chain variable region, i.e., these functional antibodies are homodimers of heavy chains only (referred to as "heavy chain antibodies") (Jespers et al., Nat. Biotechnol. 22:1161, 2004; Cortez-Retamozo et al., Cancer Res. 64:2853, 2004; Baral et al., Nature Med. 12:580, 2006; and Barthelemy et al., J. Biol. Chem. 283:3639, 2008).

[0212] In some embodiments, the extracellular domain binds to a pro-engulfment marker. In certain such embodiments, the pro-engulfment marker targeted by the extracellular domain is phosphatidylserine (PtdSer), ICAM-3, oxidized low density lipoprotein, calreticulin, annexin I, complement C1q, or thrombospondin. In further embodiments, the extracellular domain that binds to a pro-engulfment marker is derived from an endogenous engulfment receptor or a soluble bridging molecule for an engulfment receptor (e.g., GAS6, Protein S, MFG-E8). In some embodiments, the entire extracellular portion (for membrane spanning molecules), the entire bridging molecule, or a truncated portion of an engulfment receptor or bridging molecule is used, provided that the truncated portion retains sufficient binding activity to the pro-engulfment marker (i.e., is a functional variant). In further embodiments, the extracellular portion of an engulfment receptor or bridging molecule used for the extracellular domain is a variant of the entire extracellular portion (for membrane spanning molecules), the entire bridging molecule, or a truncated portion of the engulfment receptor or bridging molecule, provided that the variant retains sufficient binding activity to the pro-engulfment marker (i.e., is a functional variant).

[0213] In some embodiments, the extracellular domain includes a T-cell immunoglobulin and mucin domain 1 (Tim1), T-cell immunoglobulin and mucin domain 4 (Tim4), T-cell immunoglobulin and mucin domain 3 (Tim3), stabilin-2, RAGE, or Fc receptor (FcR) extracellular domain. In specific embodiments, an FcR extracellular domain can include a binding domain from Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, or Fc.alpha.R1. In further embodiments, the extracellular domain can include a PtdSer binding domain from Tim1, Tim4, Tim3, stabilin-2, receptor for advanced glycation endproducts (RAGE), brain-specific angiogenesis inhibitor 1 (BAI1), Milk Fat Globule-EGF Factor 8 Protein (MFG-E8) (e.g., a FA58C2 domain that mediates high affinity binding to PtdSer), Growth Arrest Specific 6 (GAS6), protein S, protein C, Factor II, Factor VII, Factor IX, Factor X, Beta 2-glycoprotein I, .alpha.5.beta.3 integrin and other integrins, CR3 complement receptor, CR4 complement receptor, CD14, CD93, annexin V, phosphatidylserine receptor (PSr), prothrombin, or scavenger receptors such as scavenger receptor B (SRB) (e.g., SRB 1 (CD36)), scavenger receptor C (SRC) (e.g., LOX-1, SRCL), scavenger receptor D (SRD) (e.g., CD68, macrosialin), and PSOX.

[0214] In some embodiments, the extracellular domain comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identical to a Fc.gamma.RI binding domain comprising an amino acid sequence of SEQ ID NO:31 or amino acids 16-292 of SEQ ID NO:31, TIM1 binding domain comprising an amino acid sequence of SEQ ID NO:28 or amino acids 21-290 of SEQ ID NO:28, a TIM4 binding domain comprising an amino acid sequence of SEQ ID NO:29 or amino acids 25-314 of SEQ ID NO:29, a TIM3 binding domain comprising an amino acid sequence of SEQ ID NO: 34 or amino acids 22-202 of SEQ ID NO:34, a FA58C2 binding domain comprising an amino acid sequence of SEQ ID NO: 30, a GAS6 binding domain comprising an amino acid sequence of SEQ ID NO: 32 or amino acids 31-94 of SEQ ID NO:32, a BAI1 binding domain comprising an amino acid sequence of SEQ ID NO: 117, or a protein S binding domain comprising an amino acid sequence of SEQ ID NO:33 or amino acids 25-87 of SEQ ID NO:33. In certain other embodiments, the extracellular domain is encoded by a polynucleotide sequence that comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identical to a polynucleotide encoding Fc.gamma.RI binding domain according to SEQ ID NO:4, a polynucleotide encoding a TIM1 binding domain according to SEQ ID NO: 1, a polynucleotide encoding a TIM4 binding domain according to SEQ ID NO:2, a polynucleotide encoding a TIM3 binding domain according to SEQ ID NO:7, a polynucleotide encoding FA58C2 binding domain according to SEQ ID NO:3, a polynucleotide encoding a GAS6 binding domain according to SEQ ID NO:5, a polynucleotide encoding a BAI1 binding domain according to SEQ ID NO: 135, or a polynucleotide sequence encoding a protein S binding domain according to SEQ ID NO:6.

[0215] In other embodiments, the extracellular domain is derived from least one of the following: CD14, which binds to ICAM3; a scavenger receptor extracellular domain, which binds to oxidized LDL; a lectin, which binds to altered sugars; CD36, which binds to thrombospondin; or LRP1/CD91 or a lectin moiety, which binds to calreticulin.

[0216] In still other embodiments, the extracellular domain includes an antibody or antigen binding fragment thereof, such as a single chain Fv fragment (scFv) that comprises VH and VL regions, specific for a target molecule of interest. In certain embodiments, the antibody is chimeric, human, or humanized. In further embodiments, the VH and VL regions are human or humanized. In particular embodiments, the extracellular domain is an antibody or antigen binding portion thereof that is specific for a pro-engulfment marker. Antibodies specific for phosphatidylserine are known in the art (see, U.S. Pat. No. 7,247,303; Khogeer et al., 2015, Lupus 24:186-90; Gerber et al., 2015, Am. J. Nucl. Med. Mol. Imaging, 5:493-503, each of which is incorporated by reference in its entirety). In particular embodiments, a target molecule of interest is a tumor antigen, for example CD138, CD38, CD33, CD123, CD72, CD79a, CD79b, mesothelin, PSMA, BCMA, ROR1, MUC-16, LCAM, CD22, CD19, CD20, CD23, CD24, CD37, CD30, CA125, CD56, c-Met, EGFR, GD-3, HPV E6, HPV E7, MUC-1, HER2, folate receptor .alpha., CD97, CD171, CD179a, CD44v6, WT1, VEGF-.alpha., VEGFR1, IL-13R.alpha.1, IL-13R.alpha.2, IL-1 IR.alpha., PSA, FcRH5, NKG2D ligand, NY-ESO-1, TAG-72, CEA, ephrin A2, ephrin B2, Lewis A antigen, Lewis Y antigen, MAGE, MAGE-A1, RAGE-1, folate receptor .beta., EGFRviii, VEGFR-2, LGR5, SSX2, AKAP-4, FLT3, fucosyl GM1, GM3, o-acetyl-GD2, and GD2, and exemplary V.sub.H and V.sub.L regions include the segments of anti-CD138, -CD38, -CD33, -CD123, -CD72, -CD79a -CD79b, -mesothelin, -PSMA, -BCMA, -ROR1, -MUC-16, -LCAM, -CD22, -CD19, -CD20, -CD23, -CD24, -CD37, -CD30, -CA125, -CD56, -c-Met, -EGFR, -GD-3, -HPV E6, -HPV E7, -MUC-1, -HER2, -folate receptor .alpha., -CD97, -CD171, -CD179a, -CD44v6, -WT1, -VEGF-.alpha., -VEGFR1, -IL-13R.alpha.1, -IL-13R.alpha.2, -IL-11R.alpha., -PSA, -FcRH5, -NKG2D ligand, -NY-ESO-1, -TAG-72, -CEA, -ephrin A2, -ephrin B2, -Lewis A antigen, -Lewis Y antigen, -MAGE, -MAGE-A1, -RAGE-1, -folate receptor 3, -EGFRviii, -VEGFR-2, -LGR5, -SSX2, -AKAP-4, -FLT3, -fucosyl GM1, -GM3, -o-acetyl-GD2, and -GD2 specific monoclonal antibodies, respectively.

[0217] In further embodiments, the extracellular domain includes a Fab specific for a target of interest. In such embodiments, targets of interest include CD138, CD38, CD33, CD123, CD72, CD79a, CD79b, mesothelin, PSMA, BCMA, ROR1, MUC-16, L1CAM, CD22, CD19, CD20, CD23, CD24, CD37, CD30, CA125, CD56, c-Met, EGFR, GD-3, HPV E6, HPV E7, MUC-1, HER2, folate receptor .alpha., CD97, CD171, CD179a, CD44v6, WT1, VEGF-.alpha., VEGFR1, IL-13R.alpha.1, IL-13R.alpha.2, IL-1IR.alpha., PSA, FcRH5, NKG2D ligand, NY-ESO-1, TAG-72, CEA, ephrin A2, ephrin B2, Lewis A antigen, Lewis Y antigen, MAGE, MAGE-A1, RAGE-1, folate receptor 3, EGFRviii, VEGFR-2, LGR5, SSX2, AKAP-4, FLT3, fucosyl GM1, GM3, o-acetyl-GD2, and GD2, and Fab regions include portions of anti-CD138, -CD38, -CD33, -CD123, -CD72, -CD79a, -CD79b, -mesothelin, -PSMA, -BCMA, -ROR1, -MUC-16, -LCAM, -CD22, -CD19, -CD20, -CD23, -CD24, -CD37, -CD30, -CA125, -CD56, -c-Met, -EGFR, -GD-3, -HPV E6, -HPV E7, -MUC-1, -HER2, -folate receptor .alpha., -CD97, -CD171, -CD79a, -CD44v6, -WT1, -VEGF-.alpha., -VEGFR1, -IL-13R.alpha., -IL-13R.alpha.2, -IL-11R.alpha., -PSA, -FcRH5, -NKG2D ligand, -NY-ESO-1, -TAG-72, -CEA, -ephrin A2, -ephrin B2, -Lewis A antigen, -Lewis Y antigen, -MAGE, MAGE-A1, -RAGE-1, -folate receptor .beta., -EGFRviii, -VEGFR-2, -LGR5, -SSX2, AKAP-4, -FLT3, -fucosyl GM1, -GM3, -o-acetyl-GD2, and -GD2 specific monoclonal antibodies, respectively.

[0218] A target molecule, which is specifically bound by an extracellular domain of a CER of the present disclosure, may be found on or in association with a cell of interest ("target cell"). Exemplary target cells include a cancer cell, a cell associated with an autoimmune disease or disorder or with an inflammatory disease or disorder, and an infectious microbe (e.g., bacteria, virus, or fungi), or infected cell (e.g., virus-infected cell). A cell of an infectious organism, such as a mammalian parasite, is also contemplated as a target cell.

[0219] In some embodiments, the extracellular domain optionally comprises an extracellular, non-signaling spacer or linker domain. Where included, such a spacer or linker domain may position the binding domain away from the host cell surface to further enable proper cell/cell contact, binding, and activation. An extracellular spacer domain is generally located between the extracellular binding domain and the transmembrane domain. The length of the extracellular spacer may be varied to optimize target molecule binding based on the selected target molecule, selected binding epitope, binding domain size and affinity (see, e.g., Guest et al., J. Immunother. 28:203-11, 2005; PCT Publication No. WO 2014/031687). In certain embodiments, an extracellular spacer domain is an immunoglobulin hinge region (e.g., IgG1, IgG2, IgG3, IgG4, IgA, IgD). An immunoglobulin hinge region may be a wild type immunoglobulin hinge region or an altered wild type immunoglobulin hinge region. An altered IgG.sub.4 hinge region is described in PCT Publication No. WO 2014/031687, which hinge region is incorporated herein by reference in its entirety. In a particular embodiment, an extracellular spacer domain comprises a modified IgG.sub.4 hinge region having an amino acid sequence of ESKYGPPCPPCP (SEQ ID NO:67). Other examples of hinge regions that may be used in the CERs described herein include the hinge region present in the extracellular regions of type 1 membrane proteins, such as CD8a, CD4, CD28 and CD7, which may be wild-type or variants thereof. In further embodiments, an extracellular spacer domain comprises all or a portion of an immunoglobulin Fc domain selected from: a CH1 domain, a CH2 domain, a CH3 domain, or combinations thereof (see, e.g., PCT Publication WO2014/031687, which spacers are incorporated herein by reference in their entirety). In yet further embodiments, an extracellular spacer domain may comprise a stalk region of a type II C-lectin (the extracellular domain located between the C-type lectin domain and the transmembrane domain). Type II C-lectins include CD23, CD69, CD72, CD94, NKG2A, and NKG2D. In yet further embodiments, an extracellular spacer domain may be derived from MERTK.

Engulfment Signaling Domain

[0220] The engulfment signaling domain of a CER is an intracellular effector domain and is capable of transmitting functional signals to a cell in response to binding of the extracellular domain of the CER to a target molecule. In certain embodiments, an engulfment signaling domain may include one or more homeostatic engulfment signaling domains, one or more pro-inflammatory signaling domains, or both a homeostatic signaling domain and a pro-inflammatory signaling domain.

[0221] In certain embodiments, an engulfment signaling domain is an intracellular signaling domain of an endogenous engulfment receptor. Examples of endogenous engulfment receptors from which engulfment signaling domains can be derived include Mer tyrosine kinase (MERTK), Tyro3 protein tyrosine kinase, Axl receptor tyrosine kinase, BAI1, mannose receptor C-type 1 (MRC1), and Fc receptor (FcR) (e.g., Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, or Fc.alpha.R1). In other embodiments, an engulfment signaling domain is an intracellular signaling domain of an endogenous kinase or adaptor protein associated with a signaling pathway during phagocytosis. Examples of kinases associated with phagocytic signaling pathway include spleen associated tyrosine kinase (SYK), zeta chain of T cell receptor associated protein kinase 70 (Zap70), and phosphoinositide 3-kinase (PI3K).

[0222] The engulfment signaling domain may be any portion of an engulfment signaling molecule that retains sufficient signaling activity. In some embodiments, a full length or full length intracellular component of an engulfment signaling molecule is used. In some embodiments, a truncated portion of an engulfment signaling molecule or intracellular component of an engulfment signaling molecule is used, provided that the truncated portion retains sufficient signal transduction activity. In further embodiments, an engulfment signaling domain is a variant of an entire or truncated portion of an engulfment signaling molecule, provided that the variant retains sufficient signal transduction activity (i.e., is a functional variant).

[0223] In certain embodiments, the engulfment signaling domain includes a homeostatic engulfment signaling domain, for example an MRC1 signaling domain, an ItgB5 signaling domain, a MERTK signaling domain, a Tyro3 signaling domain, an Axl signaling domain, a BAI1 signaling domain, or an ELMO signaling domain. In more particular embodiments, the engulfment signaling domain comprises a homeostatic engulfment signaling domain that comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identical to an MRC1 signaling domain comprising an amino acid sequence of SEQ ID NO:56, an ItgB5 signaling domain comprising an amino acid sequence of SEQ ID NO: 114, a MERTK signaling domain comprising an amino acid sequence of SEQ ID NO:69, a Tyro3 signaling domain comprising an amino acid sequence of SEQ ID NO:45, an Axl signaling domain comprising an amino acid sequence of SEQ ID NO:44, a BAI1 signaling domain comprising an amino acid sequence of SEQ ID NO: 136, or an ELMO signaling domain comprising an amino acid sequence of SEQ ID NO: 120. In other embodiments, the engulfment signaling domain includes a homeostatic engulfment signaling domain and the homeostatic engulfment signaling domain is encoded by a polynucleotide sequence that comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identical to a polynucleotide encoding a MRC1 signaling domain according to SEQ ID NO:55, a polynucleotide encoding a ItgB5 signaling domain according to SEQ ID NO: 137, a polynucleotide encoding a MERTK signaling domain according to SEQ ID NO:138, a polynucleotide encoding a Tyro3 signaling domain according to SEQ ID NO: 18, a polynucleotide encoding an Axl signaling domain according to SEQ ID NO:17, a polynucleotide encoding a BAI1 signaling domain according to SEQ ID NO: 139, or polynucleotide encoding an ELMO signaling domain according to SEQ ID NO: 140.

[0224] In certain embodiments, signaling by the homeostatic engulfment signaling domain results in expression of at least one of an anti-inflammatory cytokine and immunosuppressive cytokine. In particular embodiments, the at least one of anti-inflammatory cytokine and immunosuppressive cytokine is TGF-3, IL-10, or both.

[0225] In certain embodiments, the engulfment signaling domain includes a pro-inflammatory engulfment signaling domain, for example a Traf6 signaling domain, a Syk signaling domain, a MyD88 signaling domain, a truncated MyD88 signaling domain (e.g., comprising a death domain but lacking a Toll/interleukin-1 receptor (TIR) homology domain), a Zap70 signaling domain, a PI3K signaling domain, an FcR signaling domain (including an Fc.gamma.R1 signaling domain, an Fc.gamma.R2A signaling domain, an Fc.gamma.R2C signaling domain, Fc.gamma.R2B2 signaling domain, an Fc.gamma.R3A signaling domain, Fc.gamma.R2C signaling domain, Fc.gamma.R3A signaling domain, Fc.epsilon.R1 signaling domain, and Fc.alpha.R1 signaling domain), a B-cell activating factor receptor (BAFF-R) signaling domain, a DAP12 (also referred to as TYRO Protein Tyrosine Kinase Binding Protein (TYROBP)) signaling domain, an NFAT Activating Protein With ITAM Motif 1 (NFAM1) signaling domain, or a CD79b signaling domain.

[0226] In particular embodiments, the engulfment signaling domain includes a pro-inflammatory engulfment signaling domain that comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identical to a Traf6 signaling domain comprising an amino acid sequence of SEQ ID NO:54, a Syk signaling domain comprising an amino acid sequence of SEQ ID NO:46, a MyD88 signaling domain comprising an amino acid sequence of SEQ ID NO:53, a truncated MyD88 signaling domain comprising an amino acid sequence of SEQ ID NO:78, a Zap70 signaling domain comprising an amino acid sequence of SEQ ID NO: 47, a Fc.epsilon.RI.gamma. signaling domain comprising an amino acid sequence of SEQ ID NO:88, an Fc.gamma.R1 signaling domain comprising an amino acid sequence of SEQ ID NO:48, an Fc.gamma.R2A signaling domain comprising an amino acid sequence of SEQ ID NO:49, an Fc.gamma.R2C signaling domain comprising an amino acid sequence of SEQ ID NO:50, an Fc.gamma.R3A signaling domain comprising an amino acid sequence of SEQ ID NO:51, a BAFF-R signaling domain comprising an amino acid sequence of SEQ ID NO:94, a DAP12 signaling domain comprising an amino acid sequence of SEQ ID NO:82, a NFAM1 signaling domain comprising an amino acid sequence of SEQ ID NO:92, a truncated NFAM1 signaling domain comprising an amino acid sequence of SEQ ID NO: 132, or a CD79b signaling domain comprising an amino acid sequence of SEQ ID NO:97.

[0227] In other embodiments, the engulfment signaling domain includes a pro-inflammatory engulfment signaling domain and the pro-inflammatory signaling domain is provided by a polynucleotide sequence that comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100%0/identical to a polynucleotide encoding a Traf6 signaling domain according to SEQ ID NO:27, a polynucleotide encoding a Syk signaling domain according to SEQ ID NO: 19, a polynucleotide encoding a MyD88 signaling domain according to SEQ ID NO:26, a polynucleotide encoding a truncated MyD88 signaling domain according to SEQ ID NO:99, a polynucleotide encoding a Zap70 according to SEQ ID NO:20, a polynucleotide encoding a Fc.epsilon.RI.gamma. signaling domain according to SEQ ID NO: 141, a polynucleotide encoding an Fc.gamma.R1 signaling domain according to SEQ ID NO:21, a polynucleotide encoding an Fc.gamma.R2A signaling domain according to SEQ ID NO:22, a polynucleotide encoding an Fc.gamma.R2C signaling domain according to SEQ ID NO:23, a polynucleotide encoding an Fc.gamma.R3A signaling domain according to SEQ ID NO:24, a polynucleotide encoding a BAFF-R signaling domain according to SEQ ID NO: 126, a polynucleotide encoding a DAP12 signaling domain according to SEQ ID NO: 127, a polynucleotide encoding a NFAM1 signaling domain according to SEQ ID NO: 129, or a polynucleotide encoding a CD79b signaling domain according to SEQ ID NO: 128.

[0228] In further embodiments, signaling by the pro-inflammatory engulfment signaling domain results in expression of at least one of an inflammatory cytokine, an inflammatory chemokine, or a co-stimulatory cell surface marker. In yet further embodiments, the inflammatory cytokine is TNF.alpha., IL-1, IL-6, IL-12, or IL-23; the inflammatory chemokine is CCL5 (RANTES), CXCL9, or CXCL10; and the co-stimulatory cell surface marker is CD80, CD86, HLA-DR, CD40, HVEM, or 4-1BBL; or any combination thereof.

[0229] In yet further embodiments, the engulfment signaling domain of a CER can include more than one signaling domain. In certain such embodiments, the engulfment signaling domain includes a primary engulfment signaling domain and a secondary engulfment signaling domain. In embodiments where the engulfment signaling domain includes a primary engulfment signaling domain and a secondary engulfment signaling domain, the primary engulfment signaling domain can be a homeostatic engulfment signaling domain or a pro-inflammatory engulfment signaling domain. Similarly, the secondary engulfment signaling domain can be selected from a homeostatic engulfment signaling domain or a pro-inflammatory engulfment signaling domain. In certain embodiments, the CER includes a primary engulfment signaling domain and a secondary engulfment signaling domain that are both homeostatic engulfment signaling domains. In certain other embodiments, the CER includes a primary engulfment signaling domain and a secondary signaling domain that are both pro-inflammatory engulfment signaling domains. In still other embodiments, the CER includes a primary engulfment signaling domain that is a homeostatic engulfment signaling domain and a secondary engulfment signaling domain that is a pro-inflammatory engulfment signaling domain. In yet other embodiments, the CER includes a primary engulfment signaling domain that is a pro-inflammatory engulfment signaling domain and a secondary engulfment signaling domain that is a homeostatic engulfment signaling domain. In those embodiments where the primary engulfment signaling domain and the secondary engulfment signaling domain are both homeostatic engulfment signaling domains or both pro-inflammatory signaling domains, the primary and second engulfment signaling domains may be the same or different. In specific embodiments, the domains utilized as primary engulfment signaling domains and secondary engulfment signaling domains are selected from one or more of the specific signaling domains described herein, including MRC1, ItgB5, MERTK, ELMO, BAI1, Tyro3, Axl, Traf6, Syk, MyD88, Zap70, PI3K, Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R, DAP12, NFAM1, and CD79b.

[0230] In certain embodiments, the presence of a primary engulfment signaling domain and a secondary engulfment signaling domain enhances engulfment activity of the CER, persistence of the CER modified host cell, expansion of the CER modified host cell, or a combination thereof. In a particular embodiment, inclusion of a secondary engulfment signaling domain that is a pro-inflammatory signaling domain with a primary engulfment signaling domain that is a homeostatic engulfment signaling domain enhances engulfment activity of the CER, persistence of the CER modified host cell, expansion of the CER modified host cell, or a combination thereof.

Transmembrane Domain

[0231] The transmembrane domain connects and is positioned between the extracellular domain and the engulfment signaling domain. The transmembrane domain is a hydrophobic alpha helix that transverses the host cell membrane. The transmembrane domain may be directly fused to the binding domain or to the extracellular spacer domain if present. In certain embodiments, the transmembrane domain is derived from an integral membrane protein (e.g., receptor, cluster of differentiation (CD) molecule, enzyme, transporter, cell adhesion molecule, or the like). The transmembrane domain can be naturally associated with either the extracellular domain or the engulfment signaling domain included in the CER (e.g., a CER comprises a Tim4 binding domain and a Tim4 transmembrane domain). In certain embodiments, the transmembrane domain and the extracellular domain are derived from different molecules, the transmembrane domain and the engulfment signaling domain are derived from different molecules, or the transmembrane domain, extracellular domain, and engulfment signaling domain are all derived from different molecules.

[0232] In certain embodiments, the transmembrane domain is a Tim1 transmembrane domain, a Tim4 transmembrane domain, an FcR transmembrane domain (e.g., Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, or Fc.alpha.R1 transmembrane domain), a CD8a transmembrane domain, a MERTK transmembrane domain, an Axl transmembrane domain, a Tyro3 transmembrane domain, a BAI1 transmembrane domain, a CD4 transmembrane domain, a CD28 transmembrane domain a MRC1 transmembrane domain, or a DAP12 transmembrane domain.

[0233] In specific embodiments, the transmembrane domain comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100%0/identical to a Tim1 transmembrane domain comprising an amino acid sequence of SEQ ID NO:35, a Tim4 transmembrane domain comprising an amino acid sequence of SEQ ID NO:36, an Fc.gamma.RI transmembrane domain comprising an amino acid sequence of SEQ ID NO:37, a Fc.epsilon.RI.gamma. transmembrane domain comprising an amino acid sequence of SEQ ID NO:89, a CD8a transmembrane domain comprising an amino acid sequence of SEQ ID NO:38, a MERTK transmembrane domain comprising an amino acid sequence of SEQ ID NO:39, an Axl transmembrane domain comprising an amino acid sequence of SEQ ID NO:40, a Tyro3 transmembrane domain comprising an amino acid sequence of SEQ ID NO:41, a BAI1 transmembrane domain comprising an amino acid sequence of SEQ ID NO: 142, a CD28 transmembrane domain as set forth in an amino acid sequence of SEQ ID NO:68, a CD4 transmembrane domain comprising an amino acid sequence of SEQ ID NO:42, a MRC1 transmembrane domain comprising an amino acid sequence of SEQ ID NO: 118, or a DAP12 transmembrane domain comprising an amino acid sequence of SEQ ID NO:81. In other embodiments, the transmembrane domain is provided by a polynucleotide sequence that comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identical to a polynucleotide sequence encoding a Tim1 transmembrane domain according to SEQ ID NO:8, a polynucleotide sequence encoding a Tim4 transmembrane domain according to SEQ ID NO:9, a polynucleotide sequence encoding a Fc.epsilon.RI.gamma. transmembrane domain according to SEQ ID NO:85, a polynucleotide sequence encoding an Fc.gamma.RI transmembrane domain according to SEQ ID NO: 10, a polynucleotide sequence encoding a CD8a transmembrane domain according to SEQ ID NO: 11, a polynucleotide sequence encoding MERTK transmembrane domain according to SEQ ID NO: 12, a polynucleotide sequence encoding an Axl transmembrane domain according to SEQ ID NO: 13, a polynucleotide sequence encoding a Tyro3 transmembrane domain according to SEQ ID NO: 14, a polynucleotide sequence encoding a CD28 transmembrane domain according to SEQ ID NO: 144, a polynucleotide sequence encoding a BAI1 transmembrane domain according to SEQ ID NO: 143, a polynucleotide sequence encoding a CD4 transmembrane domain according to SEQ ID NO: 15, or a polynucleotide sequence encoding a DAP12 transmembrane domain according to SEQ ID NO: 145.

[0234] It is understood that direct fusion of one domain to another domain of a CER described herein does not preclude the presence of intervening junction amino acids. Junction amino acids may be natural or non-natural (e.g., resulting from the construct design of a chimeric protein).

Examples of CERs

[0235] The component parts of a CER as disclosed herein can be selected and arranged in various combinations to provide a desired engulfment phenotype to a host cell. In addition to inducing engulfment of a cell, microbe, or particle expressing or characterized by a molecule targeted by a CER-modified host cell, a CER as described herein may be designed to initiate a homeostatic engulfment response or pro-inflammatory engulfment response, depending upon the target cell or particle, disease state, and desired therapeutic outcome.

[0236] In one aspect, the present disclosure provides a chimeric engulfment receptor (CER) comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising a binding domain that binds to phosphatidylserine (PtdSer); an engulfment signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the engulfment signaling domain.

[0237] In certain embodiments, the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and the transmembrane domain.

[0238] In certain embodiments of a CER including an extracellular domain comprising a binding domain that binds to PtdSer, the engulfment signaling domain is a homeostatic engulfment signaling domain or a pro-inflammatory engulfment signaling domain. In certain such embodiments, the homeostatic engulfment signaling domain or the pro-inflammatory engulfment signaling domain can be selected from one or more of those described herein. In other embodiments of a CER including an extracellular domain comprising a binding domain that binds to PtdSer, the engulfment signaling domain comprises a primary engulfment signaling domain and a secondary engulfment signaling domain. The primary engulfment signaling domain and secondary engulfment signaling domain may both be homeostatic engulfment signaling domains, pro-inflammatory engulfment signaling domains, or both (in any order). In certain such embodiments, the homeostatic engulfment signaling domain or the pro-inflammatory engulfment signaling domain included in the primary signaling domain and the secondary signaling domain can be selected from one or more of the homeostatic engulfment signaling domains and the pro-inflammatory engulfment signaling domains described herein.

[0239] An embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a TIM4 PtdSer binding domain, a transmembrane domain comprising a TIM4 transmembrane domain, and an engulfment signaling domain comprising a MERTK signaling domain (also referred to herein as "CER01") (see, e.g., FIG. 6A). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:71. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:71 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:71).

[0240] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a FA58C2 PtdSer binding domain and an extracellular spacer domain comprising a modified IgG4 hinge region, a transmembrane domain comprising a CD28 transmembrane domain, and an engulfment signaling domain comprising a MERTK signaling domain (also referred to herein as "CER03") (see, e.g., FIG. 9A). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:75. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:75 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:75).

[0241] Yet another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a FA58C2 PtdSer binding domain and extracellular spacer domain comprising a modified IgG4 hinge region, a transmembrane domain comprising a CD28 transmembrane domain, and an engulfment signaling domain comprising a SYK signaling domain (also referred to as "CER04") (see, e.g., FIG. 11A). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:70. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:70 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:70).

[0242] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a TIM4 binding domain, a transmembrane domain comprising TIM4 transmembrane domain, and an engulfment signaling domain comprising a Tyro3 signaling domain (also referred to herein as "CER08"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:83. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:83 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:83).

[0243] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a TIM4 binding domain, a transmembrane domain comprising TIM4 transmembrane domain, and an engulfment signaling domain comprising a DAP12 signaling domain (also referred to herein as "CER09"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:84. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:84 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:84).

[0244] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a TIM4 binding domain, a transmembrane domain comprising DAP12 transmembrane domain, and an engulfment signaling domain comprising a DAP12 signaling domain (also referred to herein as "CER10"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:86. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:86 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:86).

[0245] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a TIM4 binding domain, a transmembrane domain comprising TIM4 transmembrane domain, and an engulfment signaling domain comprising a Axl signaling domain (also referred to herein as "CER11"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:87. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:87 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:87).

[0246] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a TIM4 binding domain, a transmembrane domain comprising TIM4 transmembrane domain, and an engulfment signaling domain comprising a Fc.epsilon.RI.gamma. signaling domain (also referred herein to as "CER12"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:90. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:90 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:90).

[0247] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a TIM4 binding domain, a transmembrane domain comprising a Fc.epsilon.RI.gamma. transmembrane domain, and an engulfment signaling domain comprising a Fc.epsilon.RI.gamma. signaling domain (also referred to herein as "CER13"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:91. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO:91 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:91).

[0248] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, and an engulfment signaling domain comprising a truncated MyD88 signaling domain comprising the death domain but lacking the TIR domain (also referred to herein as "CER15"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:79. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:79 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:79).

[0249] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, and an engulfment signaling domain comprising a MyD88 signaling domain (also referred to herein as "CER16"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:80. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:80 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:80).

[0250] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, and an engulfment signaling domain comprising a NFAM1 signaling domain (also referred to herein as "CER25"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:93. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:93 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:93).

[0251] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a truncated MyD88 signaling domain, and a secondary engulfment signaling domain comprising a BAFF-R signaling domain (also referred to herein as "CER85"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:95. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:95 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:95).

[0252] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a truncated MyD88 signaling domain, and a secondary engulfment signaling domain comprising a DAP12 signaling domain (also referred to herein as "CER86"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:96. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:96 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:96).

[0253] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising Tim4 transmembrane domain, a primary engulfment signaling domain comprising a truncated MyD88 signaling domain, and a secondary engulfment signaling domain comprising a CD79b signaling domain (also referred to herein as "CER89"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:98. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:98 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:98).

[0254] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a truncated MyD88 signaling domain, and a secondary engulfment signaling domain comprising a NFAM1 signaling domain (also referred to herein as "CER90"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 100. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 100 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 100).

[0255] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a MERTK signaling domain, and a secondary engulfment signaling domain comprising a CD79b signaling domain (also referred to herein as "CER95"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 101. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 101 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:101).

[0256] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a MERTK signaling domain, and a secondary engulfment signaling domain comprising a NFAM1 signaling domain (also referred to herein as "CER96"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 102. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 102 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 102).

[0257] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a MERTK signaling domain, and a secondary engulfment signaling domain comprising a BAFF-R signaling domain (also referred to herein as "CER93"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 103. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 103 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 103).

[0258] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a BAFF-R signaling domain, and a secondary engulfment signaling domain comprising a truncated MyD88 signaling domain (also referred to herein as "CER8T"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 130. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 130 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 130).

[0259] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a DAP12 signaling domain, and a secondary engulfment signaling domain comprising a truncated MyD88 signaling domain (also referred to herein as "CER88"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 131. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:131 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:131).

[0260] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a MERTK signaling domain, and a secondary engulfment signaling domain comprising a truncated MyD88 signaling domain (also referred to herein as "CER92"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 133. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 133 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 133).

[0261] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a MERTK signaling domain, and a secondary engulfment signaling domain comprising a DAP12 signaling domain (also referred to herein as "CER94"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 134. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 134 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 134).

[0262] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a MERTK signaling domain, and a secondary engulfment signaling domain comprising a NFAM1 signaling domain (also referred to herein as "CER96"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 102. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO: 102 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:102).

[0263] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a MERTK signaling domain, and a secondary engulfment signaling domain comprising a truncated NFAM1 signaling domain (also referred to herein as "CER96 with truncated NFAM1"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 116. In some embodiments, the CER mature polypeptide comprises an amino acid sequence of SEQ ID NO: 116 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:116).

[0264] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising a BAFFR signaling domain, and a secondary engulfment signaling domain comprising a truncated MyD88 signaling domain (also referred to herein as "CER8T"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 130. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 130 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 130).

[0265] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising an Axl signaling domain, and a secondary engulfment signaling domain comprising a DAP12 signaling domain (also referred to herein as "CER9T"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 152. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 152 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 152).

[0266] Another embodiment of a CER including an extracellular domain comprising a binding domain that binds to PtdSer comprises an extracellular domain comprising a Tim4 binding domain, a transmembrane domain comprising a Tim4 transmembrane domain, a primary engulfment signaling domain comprising an Axl signaling domain, and a secondary engulfment signaling domain comprising a CD79b signaling domain (also referred to herein as "CER98"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 153. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 153 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 153).

[0267] In another aspect, the present disclosure provides a CER comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising a binding domain that binds to a pro-engulfment marker or target antigen; a pro-inflammatory engulfment signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the pro-inflammatory engulfment signaling domain. Such CERs are specifically "polarized" to provide an inflammatory or immunogenic engulfment phenotype upon binding a target molecule (e.g., pro-engulfment marker or target antigen).

[0268] In certain embodiments of a CER including a pro-inflammatory engulfment signaling domain, the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and the transmembrane domain.

[0269] In yet another aspect, the present disclosure provides a CER comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising a binding domain that binds to a pro-engulfment marker or target antigen; an engulfment signaling domain comprising a primary engulfment signaling domain and a secondary engulfment signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the pro-inflammatory engulfment signaling domain. The primary engulfment signaling domain and secondary engulfment signaling domain may both be homeostatic engulfment signaling domains, pro-inflammatory engulfment signaling domains, or both (in any order).

[0270] In certain embodiments of a CER including an engulfment signaling domain comprising a primary engulfment signaling domain and a secondary engulfment signaling domain, the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and the transmembrane domain.

[0271] In yet another aspect, the present disclosure provides a CER comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising an scFv that binds to a pro-engulfment marker or target antigen; an engulfment signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the engulfment signaling domain, wherein the transmembrane domain and engulfment signaling domain are each derived from a different molecule.

[0272] In certain embodiments of a CER that includes an extracellular domain comprising an scFv that binds to a pro-engulfment marker or target antigen, the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and the transmembrane domain.

[0273] An embodiment of a CER that includes an extracellular domain comprising an scFv that binds to a pro-engulfment marker or target antigen comprises an extracellular domain comprising a scFv binding domain specific for CD19 (e.g., FMC63 scFv (SEQ ID NO:66)) and an extracellular spacer domain comprising a modified IgG4 hinge region; an engulfment signaling domain comprising a MERTK signaling domain; and a transmembrane domain comprising a CD28 transmembrane domain positioned between and connecting the extracellular domain and the engulfment signaling domain; wherein the extracellular spacer domain is positioned between the binding domain and the transmembrane domain (also referred to as "CER40") (see, e.g., FIG. 13A). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO:64. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO:64 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO:64).

[0274] Another of a CER that includes an extracellular domain comprising an scFv that binds to a pro-engulfment marker or target antigen comprises an extracellular domain comprising an scFv specific for mesothelin (e.g., M912 scFv, amino acids 23-264 of SEQ ID NO:106, signal peptide at amino acids 1-22 of SEQ ID NO:106) and an extracellular spacer domain comprising a modified IgG4 hinge region; an engulfment signaling domain comprising a truncated MyD88 signaling domain; and a transmembrane domain comprising a Tim4 transmembrane domain positioned between and connecting the extracellular domain and the engulfment signaling domain; wherein the extracellular spacer domain is positioned between the scFv and the transmembrane domain (also referred to herein as "CER50"). In certain embodiments, such a CER comprises an amino acid sequence of SEQ ID NO: 107. In some embodiments, the CER mature polypeptide sequence comprises an amino acid sequence of SEQ ID NO: 107 without the signal peptide sequence (amino acids 1-22 of SEQ ID NO: 107).

[0275] In certain embodiments, following binding of a CER expressed on the surface of a host cell to its cognate target molecule, lateral clustering of CERs occurs on the host cell surface, increasing the local CER concentration. Clustering is driven by the presence of multivalent ligands on the target cell or particle surface.

[0276] In certain embodiments, following binding of a CER expressed on the surface of a host cell to its cognate target molecule, dimerization or multimerization of the CERs occurs, bringing together intracellular engulfment signaling domains, which then become targets of intracellular kinases.

[0277] In certain embodiments, a CER of the present disclosure when expressed on the surface of a host cell is capable of tethering, internalizing, and processing (degrading) a target molecule or particle (e.g., phagocytosing a target). In other embodiments, a CER of the present disclosure is capable of tethering and internalizing a target molecule or particle (e.g, engulfing a target). In some embodiments, the target cell or particle within the phagosome may be discharged before or during phagosome maturation. Moreover, internalizing may comprise internalizing the whole cell or particle that is bound by the extracellular domain of the CER, or may comprise internalization of a piece or portion of the cell or particle that is bound by the extracellular domain of the CER.

[0278] In certain embodiments, a CER of the present disclosure tethers a target molecule or particle without internalization. A host cell expressing a CER may engulf or be tethered to multiple target cells or particles. Without wishing to be bound by theory, even in the absence of internalization and degradation of the target cell or particle, tethering of a target cell or particle by a host cell expressing a CER may result in degradation of the target cell or particle or promote an inflammatory environment, which is desirable in certain therapeutic contexts (e.g., cancer).

[0279] Embodiments of CERs according to the present description are illustrated in Tables 1-3, FIGS. 6A, 9A, 10A, 11A, 12A, 13A, 13B, Sequence Listing, and the examples.

Host Cells and Nucleic Acids

[0280] In certain aspects, the present disclosure provides nucleic acid molecules that encode any one or more of the CERs described herein. The nucleic acid sequences encoding a desired CER can be obtained or produced using recombinant methods known in the art using standard techniques, such as by screening libraries from cells expressing the desired sequence or a portion thereof, by deriving the sequence from a vector known to include the same, or by isolating the sequence or a portion thereof directly from cells or tissues containing the same. Alternatively, the sequence of interest can be produced synthetically, rather than being cloned.

[0281] Polynucleotides encoding the CER compositions provided herein may be derived from any animal, such as humans, primates, cows, horses, sheep, dogs, cats, mice, rats, rabbits, guinea pigs, or pigs. In certain embodiments, a polynucleotide encoding the CER is from the same animal species as the host cell into which the polynucleotide is inserted.

[0282] Polynucleotides encoding the CER compositions provided herein may also include a sequence encoding a signal peptide (also referred to as leader peptide or signal sequence) at the amino terminal end of the CER for targeting of the precursor protein to the secretory pathway. The signal peptide is optionally cleaved from the N-terminus of the extracellular domain during cellular processing and localization of the CER to the cell membrane. A polypeptide from which a signal peptide sequence has been cleaved or removed may also be called a mature polypeptide. Examples of signal peptides that may be used in the CERs of the present disclosure include signal peptides derived from endogenous secreted proteins, including, e.g., GM-CSF (amino acid sequence of SEQ ID NO:65), Tim4 (amino acid sequence of SEQ ID NO:72). In certain embodiments, polynucleotide or polypeptide sequences of CERs of the present disclosure comprise sequences for mature polypeptides. It is understood by persons of skill in the art that for sequences disclosed herein that include a signal peptide sequence, the signal peptide sequence may be replaced with another signal peptide that is capable of trafficking the encoded protein to the extracellular membrane.

[0283] In certain embodiments, a nucleic acid molecule encoding a CER of the present disclosure is codon optimized for efficient expression in a target host cell.

[0284] Nucleic acid molecules encoding a desired CER can be inserted into an appropriate vector (e.g., viral vector, non-viral plasmid vector, and non-viral vectors, such as lipid-based DNA vectors, modified mRNA (modRNA), self-amplifying mRNA, CELiD, and transposon-mediated gene transfer (PiggyBac, Sleeping Beauty)) for introduction in a host cell of interest (e.g., a T cell, a natural killer cell, a B cell, a lymphocyte precursor cell, an antigen presenting cell, a Langerhans cell, or a myeloid cell). Nucleic acid molecules encoding a CER of the present disclosure can be cloned into any suitable vector, such as an expression vector, a replication vector, a probe generation vector, or a sequencing vector. In certain embodiments, a nucleic acid sequence encoding the extracellular domain, a nucleic acid sequence encoding the transmembrane domain, and a nucleic acid sequence encoding the engulfment signaling domain are joined together in a single polynucleotide and then inserted into a vector. In other embodiments, a nucleic acid sequence encoding the extracellular domain, a nucleic acid sequence encoding the transmembrane domain, and a nucleic acid sequence encoding the engulfment signaling domain may be inserted separately in a vector such that the resulting amino acid sequence produces a functional CER. A vector that encodes a CER is referred to herein as a "CER vector."

[0285] In certain embodiments, a vector comprises a nucleic acid molecule encoding one CER. In other embodiments, a vector comprises one or more nucleic acid molecules encoding two or more CERs. In one embodiment, two or more nucleic acid molecules each encoding a CER may be cloned sequentially into a vector at different multiple cloning sites, with each CER expressed under the regulation of different promoters. In another embodiment, a single nucleic acid molecule encoding multiple CERs is cloned into a cloning site and expressed from a single promoter, with each CER separated from each other by an IRES or viral 2A peptide sequence to allow for co-expression of multiple genes from a single open reading frame (e.g., a multicistronic vector). In certain embodiments, a viral 2A peptide is T2A (SEQ ID NO: 147), P2A (SEQ ID NO: 104), E2A (SEQ ID NO: 148), or F2A (SEQ ID NO: 149).

[0286] In some embodiments, vectors that allow long-term integration of a transgene and propagation to daughter cells are utilized. Examples include viral vectors such as, adenovirus, adeno-associated virus, vaccinia virus, herpes viruses, Cytomegalovirus, pox virus, or retroviral vectors, such as lentiviral vectors. Vectors derived from lentivirus can be used to achieve long-term gene transfer and have added advantages over vectors including the ability to transduce non-proliferating cells, such as hepatocytes, and low immunogenicity.

[0287] In certain embodiments, a CER vector can be constructed to optimize spatial and temporal control. For example, CER vector can include promoter elements to optimize spatial and temporal control. In some embodiments, a CER vector includes tissue specific promoters or enhancers that enable specific induction of a CER to an organ or a pathologic microenvironment, such as tumor or infected tissue. An "enhancer" is an additional promoter element that can function either cooperatively or independently to activate transcription. In other embodiments, a CER vector includes a constitutive promoter. In still other embodiments, a CER vector includes an inducible promoter.

[0288] In further embodiments, a CER vector can include a homing receptor, such as CCR4 or CXCR4, to improve homing and antitumor activity in vivo.

[0289] Where temporal control is desired, a CER vector may include an element that allows for inducible depletion of transduced cells. For example, such a vector may include an inducible suicide gene. A suicide gene may be an apoptotic gene or a gene that confers sensitivity to an agent (e.g., drug), such as chemically inducible caspase 9 (iCASP9), chemically inducible Fas, or HSV-TK (confers sensitivity to ganciclovir). In further embodiments, a CER vector can be designed to express a known cell surface antigen that, upon infusion of an associated antibody, enables depletion of transduced cells. Examples of cell surface antigens and their associated antibodies that may be used for depletion of transduced cells include CD20 and Rituximab, RQR8 (combined CD34 and CD20 epitopes, allowing CD34 selection and anti-CD20 deletion) and Rituximab, and EGFR and Cetuximab.

[0290] Inducible vector systems, such as the tetracycline (Tet)-On vector system which activates transgene expression with doxycycline (Heinz et al., Hum. Gene Ther. 2011, 22:166-76) may also be used for inducible CER expression. Inducible CER expression may be also accomplished via retention using a selective hook (RUSH) system based on streptavidin anchored to the membrane of the endoplasmic reticulum through a hook and a streptavidin binding protein introduced into the CER structure, where addition of biotin to the system leads to the release of the CER from the endoplasmic reticulum (Agaugue et al., 2015, Mol. Ther. 23(Suppl. 1):S88).

[0291] As used herein, the term "recombinant" or "non-natural" refers to an organism, microorganism, cell, nucleic acid molecule, or vector that includes at least one genetic alteration or has been modified by introduction of an exogenous nucleic acid molecule, wherein such alterations or modifications are introduced by genetic engineering. Genetic alterations include, for example, modifications introducing expressible nucleic acid molecules encoding proteins, chimeric proteins or enzymes, or other nucleic acid molecule additions, deletions, substitutions or other functional disruption of a cell's genetic material. Additional modifications include, for example, non-coding regulatory regions in which the modifications alter expression of a gene or operon. In certain embodiments, a cell, such as a T cell, obtained from a subject may be genetically modified into a non-natural or recombinant cell (e.g., a non-natural or recombinant T cell) by introducing a nucleic acid that encodes a CER as described herein and whereby the cell expresses a cell surface located CER.

[0292] A vector that encodes a core virus is referred to herein as a "viral vector." There are a large number of available viral vectors suitable for use with the compositions of the instant disclosure, including those identified for human gene therapy applications (see Pfeifer and Verma, Ann. Rev. Genomics Hum. Genet. 2:177, 2001). Suitable viral vectors include vectors based on RNA viruses, such as retrovirus-derived vectors, e.g., Moloney murine leukemia virus (MLV)-derived vectors, and include more complex retrovirus-derived vectors, e.g., lentivirus-derived vectors. HIV-1-derived vectors belong to this category. Other examples include lentivirus vectors derived from HIV-2, FIV, equine infectious anemia virus, SIV, and Maedi-Visna virus (ovine lentivirus). Methods of using retroviral and lentiviral viral vectors and packaging cells for transducing mammalian host cells with viral particles containing chimeric receptor transgenes are known in the art and have been previous described, for example, in U.S. Pat. No. 8,119,772; Walchli et al., PLoS One 6:327930, 2011; Zhao et al., J. Immunol. 174:4415, 2005; Engels et al., Hum. Gene Ther. 14:1155, 2003; Frecha et al., Mol. Ther. 18:1748, 2010; Verhoeyen et al., Methods Mol. Biol. 506:97, 2009. Retroviral and lentiviral vector constructs and expression systems are also commercially available.

[0293] In certain embodiments, a viral vector is used to introduce a non-endogenous nucleic acid sequence encoding a CER specific for a target. A viral vector may be a retroviral vector or a lentiviral vector. A viral vector may also include nucleic acid sequences encoding a marker for transduction. Transduction markers for viral vectors are known in the art and include selection markers, which may confer drug resistance, or detectable markers, such as fluorescent markers or cell surface proteins that can be detected by methods such as flow cytometry. In particular embodiments, a viral vector further comprises a gene marker for transduction comprising fluorescent protein (e.g., green, yellow), an extracellular domain of human CD2, or a truncated human EGFR (encoding an amino acid sequence of SEQ ID NO: 121) (huEGFRt; see Wang et al., Blood 118:1255, 2011). When a viral vector genome comprises a plurality of nucleic acid sequences to be expressed in a host cell as separate transcripts, the viral vector may also comprise additional sequences between the two (or more) transcripts allowing bicistronic or multicistronic expression. Examples of such sequences used in viral vectors include internal ribosome entry sites (IRES), furin cleavage sites, viral 2A peptides (e.g., T2A, P2A, E2A, F2A), or any combination thereof.

[0294] FIGS. 2A and 2B provide illustrative CER vectors. The CER vectors shown in FIG. 2A contain a single engulfment signaling domain. The CER vectors shown in FIG. 2B contain an engulfment signaling domain that includes a primary engulfment signaling domain and a secondary engulfment signaling domain.

[0295] Other viral vectors also can be used for polynucleotide delivery including DNA viral vectors, including, for example adenovirus-based vectors and adeno-associated virus (AAV)-based vectors; vectors derived from herpes simplex viruses (HSVs), including amplicon vectors, replication-defective HSV and attenuated HSV (Krisky et al., Gene Ther. 5: 1517, 1998).

[0296] Other viral vectors recently developed for gene therapy uses can also be used with the compositions and methods of this disclosure. Such vectors include those derived from baculoviruses and .alpha.-viruses. (Jolly, D J. 1999. Emerging Viral Vectors. pp 209-40 in Friedmann T. ed. The Development of Human Gene Therapy. New York: Cold Spring Harbor Lab), or plasmid vectors (such as sleeping beauty or other transposon vectors). In some embodiments, a viral or plasmid vector further comprises a gene marker for transduction (e.g. green fluorescent protein, huEGFRt (encoding an amino acid sequence of SEQ ID NO:121).

[0297] In certain embodiments, gene editing methods are used to modify the host cell genome to comprise a polynucleotide encoding a CER of the present disclosure. Gene editing, or genome editing, is a method of genetic engineering wherein DNA is inserted, replaced, or removed from a host cell's genome using genetically engineered endonucleases. The nucleases create specific double-stranded breaks at targeted loci in the genome. The host cell's endogenous DNA repair pathways then repair the induced break(s), e.g., by non-homologous ending joining (NHEJ) and homologous recombination. Exemplary endonucleases useful in gene editing include a zinc finger nuclease (ZFN), a transcription activator-like effector (TALE) nuclease, a clustered regularly interspaced short palindromic repeats (CRISPR)/Cas nuclease system (e.g., CRISPR-Cas9), a meganuclease, or combinations thereof. Methods of disrupting or knocking out genes or gene expression in immune cells including B cells and T cells, using gene editing endonucleases are known in the art and described, for example, in PCT Publication Nos. WO 2015/066262; WO 2013/074916; WO 2014/059173; Cheong et al., Nat. Comm. 2016 7:10934; Chu et al., Proc. Natl. Acad. Sci. USA 2016 113:12514-12519; methods from each of which are incorporated herein by reference in their entirety.

[0298] In certain embodiments, B cells, lymphoid precursor cells, including common lymphocyte precursor cells, antigen presenting cells, including dendritic cells, Langerhans cells, a myeloid precursor cell, or mature myeloid cells are modified to comprise a non-endogenous nucleic acid molecule that encodes a CER of this disclosure.

[0299] In some embodiments, B cells are genetically modified to express one or more CERs. B cells possess certain properties that may be advantageous as host cells, including: trafficking to sites of inflammation (e.g., lymph nodes, tumors), capable of internalizing and presenting antigen, capable of costimulating T cells, highly proliferative, and self-renewing (persist for life). In certain embodiments, CER modified B cells are capable of digesting an engulfed target cell or engulfed target particle into smaller peptides and presenting them to T cells via an MHC molecule. Antigen presentation by CER modified B cells may contribute to antigen spreading of the immune response to non-targeted antigens. B cells include progenitor or precursor cells committed to the B cell lineage (e.g., pre-pro-B cells, pro-B cells, and pre-B cells); immature and inactivated B cells or mature and functional or activated B cells. In certain embodiments, B cells may be naive B cells, plasma cells, regulatory B cells, marginal zone B cells, follicular B cells, lymphoplasmacytoid cell, plasmablast cell, memory B cells, or any combination thereof. Memory B cells may be distinguished from naive B cells by expression of CD27, which is absent on naive B cells. In certain embodiments, the B cells can be primary cells or cell lines derived from human, mouse, rat, or other mammals. B cell lines are well known in the art. If obtained from a mammal, a B cell can be obtained from numerous sources, including blood, bone marrow, spleen, lymph node, or other tissues or fluids. In certain embodiments, a B cell is isolated from a tumor site (tumor infiltrating B cell). A B cell composition may be enriched or purified.

[0300] In certain embodiments, expression of an endogenous gene of the host B cell is inhibited, knocked down, or knocked out. Examples of endogenous genes that may be inhibited, knocked down, or knocked out in a B cell include a B cell receptor (BCR) gene (e.g., CD79b, IGH, IG.kappa., IG.lamda., or any combination thereof), an immune checkpoint molecule (e.g., PD-L1, PD-L2, CD80, CD86, B7-H3, B7-H4, HVEM, adenosine, GAL9, VISTA, CEACAM-1, CEACAM-3, CEACAM-5, PVRL2, PD-1, CTLA-4, BTLA, KIR, LAG3, TIM3, A2aR, CD244/2B4, CD160, TIGIT, LAIR-1, PVRIG/CD112R, or any combination thereof), or any combination thereof. Expression of a BCR gene, an immune checkpoint molecule gene, or both may be inhibited, knocked down, or knocked out at the gene level, transcriptional level, or translational level, or a combination thereof. Methods of inhibiting, knocking down, or knocking out a BCR gene, immune checkpoint molecule gene, or both may be accomplished, for example, by RNA interference agents (e.g., siRNA, shRNA, miRNA, etc.) or engineered endonucleases (e.g., CRISPR/Cas nuclease system, a zinc finger nuclease (ZFN), a Transcription Activator Like Effector nuclease (TALEN), a meganuclease, or any combination thereof). In some embodiments, an endogenous gene (e.g., a BCR gene or an immune checkpoint molecule gene) is knocked out by insertion of a polynucleotide encoding a CER of the present disclosure into the locus of the endogenous B cell gene, such as via an engineered endonuclease.

[0301] In some embodiments, cells capable of expressing a CER of this disclosure on the cell surface are T cells, including CD4.sup.+, CD8.sup.+, naive (CD45 RA+, CCR7+, CD62L+, CD27+, CD45RO-), central memory (CD45RO+, CD62L+, CD8+), effector memory (CD45RA+, CD45RO-, CCR7-, CD62L-, CD27-), virus-specific, mucosal-associated invariant, .gamma..delta. (gd), tissue resident T cells, and natural killer T cells. In certain embodiments, the T cells can be primary cells or cell lines derived from human, mouse, rat, or other mammals. If obtained from a mammal, a T cell can be obtained from numerous sources, including blood, bone marrow, lymph node, thymus, or other tissues or fluids. In certain embodiments, a T cell is isolated from a tumor site (tumor infiltrating T cell). A T cell composition may be enriched or purified. T cell lines are well known in the art, some of which are described in Sandberg et al., Leukemia 21:230, 2000. In certain embodiments, T cells that lack endogenous expression of TCR.alpha. and .beta. chains are used. Such T cells may naturally lack endogenous expression of TCR.alpha. and .beta. chains or may have been modified to block expression (e.g., T cells from a transgenic mouse that does not express TCR .alpha. and .beta. chains or cells that have been manipulated to inhibit expression of TCR .alpha. and .beta. chains) or to knockout TCR.alpha. chain, TCR chain, or both genes. In certain embodiments, cells capable of expressing a chimeric protein of this disclosure on the cell surface are not T cells or cells of a T cell lineage, but cells that are progenitor cells, stem cells or cells that have been modified to express cell surface anti-CD3.

[0302] In certain embodiments, a host T cell transfected to express a CER of this disclosure is a functional T cell, such as a virus-specific T cell, a tumor antigen specific cytotoxic T cell, a naive T cell, a memory stem T cell, a central or effector memory T cell, or a CD4+CD25+ regulatory T cell.

[0303] In certain embodiments, expression of an endogenous gene of the host T cell is inhibited, knocked down, or knocked out. Examples of endogenous genes that may be inhibited, knocked down, or knocked out in a T cell include a TCR gene (TRA, TRB, or both), HLA gene (HLA class I gene, HLA class II gene, or both), an immune checkpoint molecule (PD-L1, PD-L2, CD80, CD86, B7-H3, B7-H4, HVEM, adenosine, GAL9, VISTA, CEACAM-1, CEACAM-3, CEACAM-5, PVRL2, PD-1, CTLA-4, BTLA, KIR, LAG3, TIM3, A2aR, CD244/2B4, CD160, TIGIT, LAIR-1, PVRIG/CD112R, or any combination thereof), or any combination thereof. Expression of a TCR gene, an HLA gene, an immune checkpoint molecule gene, or any combination thereof may be inhibited, knocked down, or knocked out at the gene level, transcriptional level, or translational level, or any combination thereof. Methods of inhibited, knocked down, or knocked out a TCR gene, an HLA gene, immune checkpoint molecule gene, or any combination thereof may be accomplished, for example, by RNA interference agents (e.g., siRNA, shRNA, miRNA, etc.) or engineered endonucleases (e.g., CRISPR/Cas nuclease system, a zinc finger nuclease (ZFN), a Transcription Activator Like Effector nuclease (TALEN), a meganuclease, or any combination thereof). In some embodiments, an endogenous gene (e.g., a TCR gene, an HLA gene, or an immune checkpoint molecule gene) is knocked out by insertion of a polynucleotide encoding a CER of the present disclosure into the locus of the endogenous T cell gene, such as via an engineered endonuclease.

[0304] In certain embodiments, a host cell may be genetically modified to express one type of CER. In other embodiments, a host cell may express at least two or more different CERs.

[0305] In certain embodiments, a population of host cells that are modified to express one or more CERs may be a population of B cells, a population of T cells, a population of natural killer cells, a population of lymphoid precursor cells, including common lymphocyte precursor cells, a population of antigen presenting cells, including dendritic cells, Langerhans cells, a population of myeloid precursor cells, a population of mature myeloid cells, or any combination thereof. In a particular embodiment, the population of host cells that are modified to express one or more CERs is a population of B cells, a population of T cells, or both.

[0306] In certain embodiments, each host cell within a population of host cells expresses the same CER or set of CERs. In other embodiments, a population of host cells comprises a mixture of two or more subpopulation of host cells, wherein each subpopulation expresses a different CER or set of CERs.

[0307] In certain embodiments, a host cell that is genetically modified to express a CER may also be modified to co-express one or more small GTPases. Rho GTPases, a family of small (.about.21 k Da) signaling G proteins and also a subfamily of the Ras superfamily, regulate actin cytoskeleton organization in various cell types and promote pseudopod extension and phagosome closure during phagocytosis (see, e.g., Castellano et al., 2000, J. Cell Sci. 113:2955-2961). Engulfment requires F-actin recruitment beneath tethered cells or particles, and F-actin rearrangement to allow membrane extension resulting in cell or particle internalization. RhoGTPases include RhoA, Rac1, Rac2, RhoG, and CDC42. Other small GTPases, such as Rap1, is involved in regulation of complement mediated phagocytosis. Co-expression of a small GTPase with the CER may promote target cell or particle internalization and/or phagosome formation by the host cell. In some embodiments, a recombinant nucleic acid molecule encoding a GTPase is encoded on a separate vector than the CER-containing vector. In other embodiments, a recombinant nucleic acid molecule encoding a GTPase is encoded on the same CER-containing vector as a multicistronic expression construct. The polynucleotide sequences encoding the CER and small GTPase(s) may be separated from each other by a viral 2A peptide sequence (e.g., T2A (SEQ ID NO: 147), P2A (SEQ ID NO:104), E2A (SEQ ID NO: 148), F2A (SEQ ID NO: 149)) to allow multicistronic expression from a single open reading frame. Examples of GTPases that may be co-expressed with a CER include Rac1, Rac2, Rab5 (also referred to as Rab5a), Rab7, Rap1, RhoA, RhoG, CDC42, or any combination thereof. In specific embodiments, the GTPase comprises or is a sequence that is at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, at least 99.5%, or 100% identical to a Rac1 amino acid sequence of SEQ ID NO:76, a Rab5 amino acid sequence of SEQ ID NO:77, a Rab7 amino acid sequence of SEQ ID NO:122, a Rap1 amino acid sequence of SEQ ID NO:123, a RhoA amino acid sequence of SEQ ID NO: 124, a CDC42 amino acid sequence of SEQ ID NO: 125, or any combination thereof. In a particular embodiment of a multicistronic expression construct, an expression construct encoding a Tim4-MyD88t CER and small GTPase Rab5a separated by a P2A sequence may comprise an amino acid sequence of SEQ ID NO: 105 (CER91). In yet another particular embodiment, a CER mature polypeptide sequence comprises SEQ ID NO: 105 without the signal peptide at amino acids 1-22.

[0308] In certain embodiments, when preparing host cells, e.g., B cells or T cells, that express a CER as described herein, one or more growth factor cytokines that promote proliferation of the host cells, e.g., B cells or T cells, may be added to the cell culture. The cytokines may be human or non-human. Exemplary growth factor cytokines that may be used to promote T cell proliferation include IL-2, IL-15, or the like. Exemplary growth factor cytokines that may be used to promote B cell proliferation include CD40L, IL-2, IL-4, IL-15, IL-21, BAFF, or the like.

[0309] In further embodiments, selective gene transfer is used to localize the CER vector to a specific region or organ. In some embodiments, selective gene transfer is used to localize the CER vector to the liver or the lungs of a subject.

[0310] Prior to genetic modification of the host cells with a CER vector, a source of host cells (e.g., T cells, B cells, natural killer cells, etc.) is obtained from a subject (e.g., whole blood, peripheral blood mononuclear cells, bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue), from which host cells are isolated using methods known in the art. Specific host cell subsets can be collected in accordance with known techniques and enriched or depleted by known techniques, such as affinity binding to antibodies, flow cytometry and/or immunomagnetic selection. After enrichment and/or depletion steps and introduction of a CER, in vitro expansion of the desired modified host cells can be carried out in accordance with known techniques, or variations thereof that will be apparent those skilled in the art.

[0311] In certain embodiments, a host cell, including a T cell, a natural killer cell, a B cell, a lymphoid precursor cell, an antigen presenting cell, dendritic cell, a Langerhans cell, a myeloid precursor cell, and a mature myeloid cell, comprising a CER according to any of the embodiments described herein has a phagocytic index of about 20 to about 1,500 for a target cell. A "phagocytic index" is a measure of phagocytic activity of the transduced host cell as determined by counting the number of target cells ingested per CER modified host cell during a set period of incubation of a suspension of target cells and CER modified host cells in media. Phagocytic index may be calculated by multiplying [total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)].times.[average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] or [total number of engulfed particles/total number of counted CER modified host cells].times.[number of CER modified host cells containing engulfed particles/total number of counted CER cells].times.100. In certain embodiments, a CER modified cell has a phagocytic index of about 30 to about 1,500; about 40 to about 1,500; about 50 to about 1,500; about 75 to about 1,500; about 100 to about 1,500; about 200 to about 1,500; about 300 to about 1,500; about 400 to about 1,500; about 500 to about 1,500; about 20 to about 1,400; about 30 to about 1,400; about 40 to about 1,400; about 50 to about 1,400; about 100 to about 1,400; about 200 to about 1,400; about 300 to about 1,400; about 400 to about 1,400; about 500 to about 1,400; about 20 to about 1,300; about 30 to about 1,300; about 40 to about 1,300; about 50 to about 1,300; about 100 to about 1,300; about 200 to about 1,300; about 300 to about 1,300; about 400 to about 1,300; about 500 to about 1,300; about 20 to about 1,200; about 30 to about 1,200; about 40 to about 1,200; about 50 to about 1,200; about 100 to about 1,200; about 200 to about 1,200; about 300 to about 1,200; about 400 to about 1,200; about 500 to about 1,200; about 20 to about 1,100; about 30 to about 1,100; about 40 to about 1,100; about 50 to about 1,100; about 100 to about 1,100; about 200 to about 1,100; about 300 to about 1,100; about 400 to about 1,100; or about 500 to about 1,100; about 20 to about 1,000; about 30 to about 1,000; about 40 to about 1,000; about 50 to about 1,000; about 100 to about 1,000; about 200 to about 1,000; about 300 to about 1,000; about 400 to about 1,000; or about 500 to about 1,000; about 20 to about 750; about 30 to about 750; about 40 to about 750; about 50 to about 750; about 100 to about 750; about 200 to about 750; about 300 to about 750; about 400 to about 750; or about 500 to about 750; about 20 to about 500; about 30 to about 500; about 40 to about 500; about 50 to about 500; about 100 to about 500; about 200 to about 500; or about 300 to about 500. In further embodiments, the incubation time is from about 2 hours to about 4 hours, about 2 hours, about 3 hours, or about 4 hours. In yet further embodiments, a CER modified cell exhibits phagocytic index that is statistically significantly higher than a cell transduced with truncated EGFR control. Phagocytic index may be calculated using methods known in the art and as further described in the Examples, including quantification by flow cytometry or fluorescence microscopy.

[0312] Host cells may be from an animal, such as a primate, cow, horse, sheep, dog, cat, mouse, rat, rabbit, guinea pig, or pig. In a preferred embodiment, the animal is a human. Host cells may be obtained from a healthy subject or a subject having a disease associated with expression of an antigen.

Uses of CERs and Cells Modified to Express CERs

[0313] The present disclosure provides methods for altering the engulfment phenotype of a host cell. In one aspect, the present disclosure provides methods for producing a population of cells exhibiting an engulfment phenotype comprising introducing into a population of host cells that do not naturally exhibit an engulfment phenotype a nucleic acid molecule encoding at least one CER or a vector comprising at least one CER according to any of the embodiments described herein; and expressing the at least one CER in the population of host cells. In certain embodiments, the engulfment phenotype is phagocytosis.

[0314] In another aspect, the present disclosure provides methods for altering the engulfment phenotype of a population of cells comprising introducing into a population of host cells a nucleic acid molecule encoding at least one CER or a vector comprising at least one CER according to any of the embodiments described herein; and expressing the at least one CER in the population of host cells, wherein the at least one CER confers an engulfment phenotype specific to a pro-engulfment marker or antigenic marker (target antigen) that is not naturally targeted by the host cells. In certain embodiments, the engulfment phenotype is phagocytosis.

[0315] In yet another aspect, the present disclosure provides methods for enhancing the engulfment phenotype of a population of cells comprising introducing into a population of host cells a nucleic acid molecule encoding at least one CER or a vector comprising at least one CER according to any of the embodiments described herein; and expressing the at least one CER in the population of host cells, wherein the at least one CER is specific to a pro-engulfment marker or antigenic marker (target antigen) that is naturally targeted by the host cells and expression of the at least one CER by the host cells enhances the engulfment by the host cells of cells, microbes, or particles exhibiting the targeted pro-engulfment or antigenic marker.

[0316] CERs, nucleic acid molecules encoding CERs, vectors comprising CERs, and host cells that express CERs according to any of the embodiments described herein may also be used in a method treating a subject suffering from a disease, disorder or undesired condition. Embodiments of these methods include administering to a subject a therapeutically effective amount of a pharmaceutical composition including one or more CERs, nucleic acid molecules encoding one or more CERs, vectors comprising one or more CERs, or a population of host cells genetically modified to express one or more CERs according to the present description.

[0317] Diseases that may be treated with cells expressing a CER as described in the present disclosure include cancer, infectious diseases (viral, bacterial, fungal, protozoan infections), inflammatory, or immune diseases (e.g., autoimmune diseases, inflammatory bowel diseases, multiple sclerosis), degenerative disease (e.g., joint and cartilage), and neurodegenerative diseases (e.g., Alzheimer's disease). Adoptive immune and gene therapies are promising treatments for various types of cancer (Morgan et al., Science 314:126, 2006; Schmitt et al., Hum. Gene Ther. 20:1240, 2009; June, J. Clin. Invest. 117:1466, 2007) and infectious disease (Kitchen et al., PLoS One 4:38208, 2009; Rossi et al., Nat. Biotechnol. 25:1444, 2007; Zhang et al., PLoS Pathog. 6:e1001018, 2010; Luo et al., J. Mol. Med. 89:903, 2011).

[0318] Subjects that can be treated by the compositions and methods of the present disclosure include animals, such as humans, primates, cows, horses, sheep, dogs, cats, mice, rats, rabbits, guinea pigs, or pigs. The subject may be male or female, and can be any suitable age, including infant, juvenile, adolescent, adult, and geriatric subjects. A wide variety of cancers, including solid tumors and leukemias are amenable to the compositions and methods disclosed herein. Exemplary types of cancer that may be treated include adenocarcinoma of the breast, prostate, and colon; all forms of bronchogenic carcinoma of the lung; myeloid leukemia; melanoma; hepatoma; neuroblastoma; papilloma; apudoma; choristoma; branchioma; malignant carcinoid syndrome; carcinoid heart disease; and carcinoma (e.g., Walker, basal cell, basosquamous, Brown-Pearce, ductal, Ehrlich tumor, Krebs 2, Merkel cell, mucinous, non-small cell lung, oat cell, papillary, scirrhous, bronchiolar, bronchogenic, squamous cell, and transitional cell). Additional types of cancers that may be treated include histiocytic disorders; malignant histiocytosis; leukemia; Hodgkin's disease; immunoproliferative small; non-Hodgkin's lymphoma; plasmacytoma; multiple myeloma; plasmacytoma; reticuloendotheliosis; melanoma; chondroblastoma; chondroma; chondrosarcoma; fibroma; fibrosarcoma; giant cell tumors; histiocytoma; lipoma; liposarcoma; mesothelioma; myxoma; myxosarcoma; osteoma; osteosarcoma; chordoma; craniopharyngioma; dysgerminoma; hamartoma; mesenchymoma; mesonephroma; myosarcoma; ameloblastoma; cementoma; odontoma; teratoma; thymoma; trophoblastic tumor. Further, the following types of cancers are also contemplated as amenable to treatment: adenoma; cholangioma; cholesteatoma; cyclindroma; cystadenocarcinoma; cystadenoma; granulosa cell tumor; gynandroblastoma; hepatoma; hidradenoma; islet cell tumor; Leydig cell tumor; papilloma; sertoli cell tumor; theca cell tumor; leimyoma; leiomyosarcoma; myoblastoma; myomma; myosarcoma; rhabdomyoma; rhabdomyosarcoma; ependymoma; ganglioneuroma; glioma; medulloblastoma; meningioma; neurilemmoma; neuroblastoma; neuroepithelioma; neurofibroma; neuroma; paraganglioma; paraganglioma nonchromaffin. The types of cancers that may be treated also include angiokeratoma; angiolymphoid hyperplasia with eosinophilia; angioma sclerosing; angiomatosis; glomangioma; hemangioendothelioma; hemangioma; hemangiopericytoma; hemangiosarcoma; lymphangioma; lymphangiomyoma; lymphangiosarcoma; pinealoma; carcinosarcoma; chondrosarcoma; cystosarcoma phyllodes; fibrosarcoma; hemangiosarcoma; leiomyosarcoma; leukosarcoma; liposarcoma; lymphangiosarcoma; myosarcoma; myxosarcoma; ovarian carcinoma; rhabdomyosarcoma; sarcoma; neoplasms; nerofibromatosis; and cervical dysplasia.

[0319] Exemplifying hyperproliferative disorders amenable to CER therapy are B-cell cancers, including B-cell lymphomas (such as various forms of Hodgkin's disease, non-Hodgkins lymphoma (NHL) or central nervous system lymphomas), leukemias (such as acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), Hairy cell leukemia, B cell blast transformation of chronic myeloid leukemia) and myelomas (such as multiple myeloma). Additional B cell cancers include small lymphocytic lymphoma, B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, splenic marginal zone lymphoma, plasma cell myeloma, solitary plasmacytoma of bone, extraosseous plasmacytoma, extra-nodal marginal zone B-cell lymphoma of mucosa-associated (MALT) lymphoid tissue, nodal marginal zone B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, mediastinal (thymic) large B-cell lymphoma, intravascular large B-cell lymphoma, primary effusion lymphoma, Burkitt's lymphoma/leukemia, B-cell proliferations of uncertain malignant potential, lymphomatoid granulomatosis, and post-transplant lymphoproliferative disorder.

[0320] Inflammatory and autoimmune diseases include arthritis, rheumatoid arthritis, juvenile rheumatoid arthritis, osteoarthritis, polychondritis, psoriatic arthritis, psoriasis, dermatitis, polymyositis/dermatomyositis, inclusion body myositis, inflammatory myositis, toxic epidermal necrolysis, systemic scleroderma and sclerosis, CREST syndrome, inflammatory bowel disease, Crohn's disease, ulcerative colitis, respiratory distress syndrome, adult respiratory distress syndrome (ARDS), meningitis, encephalitis, uveitis, colitis, glomerulonephritis, allergic conditions, eczema, asthma, conditions involving infiltration of T cells and chronic inflammatory responses, atherosclerosis, autoimmune myocarditis, leukocyte adhesion deficiency, systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus, discoid lupus, lupus myelitis, lupus cerebritis, juvenile onset diabetes, multiple sclerosis, allergic encephalomyelitis, neuromyelitis optica, rheumatic fever, Sydenham's chorea, immune responses associated with acute and delayed hypersensitivity mediated by cytokines and T-lymphocytes, tuberculosis, sarcoidosis, granulomatosis including Wegener's granulomatosis and Churg-Strauss disease, agranulocytosis, vasculitis (including hypersensitivity vasculitis/angiitis, ANCA and rheumatoid vasculitis), aplastic anemia, Diamond Blackfan anemia, immune hemolytic anemia including autoimmune hemolytic anemia (AIHA), pernicious anemia, pure red cell aplasia (PRCA), Factor VIII deficiency, hemophilia A, autoimmune neutropenia, pancytopenia, leukopenia, diseases involving leukocyte diapedesis, central nervous system (CNS) inflammatory disorders, Alzheimer's disease, multiple organ injury syndrome, myasthenia gravis, antigen-antibody complex mediated diseases, anti-glomerular basement membrane disease, anti-phospholipid antibody syndrome, allergic neuritis, Behcet disease, Castleman's syndrome, Goodpasture's syndrome, Lambert-Eaton Myasthenic Syndrome, Reynaud's syndrome, Sjorgen's syndrome, Stevens-Johnson syndrome, solid organ transplant rejection, graft versus host disease (GVHD), bullous pemphigoid, pemphigus, autoimmune polyendocrinopathies, seronegative spondyloarthropathies, Reiter's disease, stiff-man syndrome, giant cell arteritis, immune complex nephritis, IgA nephropathy, IgM polyneuropathies or IgM mediated neuropathy, idiopathic thrombocytopenic purpura (ITP), thrombotic throbocytopenic purpura (TTP), Henoch-Schonlein purpura, autoimmune thrombocytopenia, autoimmune disease of the testis and ovary including autoimmune orchitis and oophoritis, primary hypothyroidism; autoimmune endocrine diseases including autoimmune thyroiditis, chronic thyroiditis (Hashimoto's Thyroiditis), subacute thyroiditis, idiopathic hypothyroidism, Addison's disease, Grave's disease, autoimmune polyglandular syndromes (or polyglandular endocrinopathy syndromes), Type I diabetes also referred to as insulin-dependent diabetes mellitus (IDDM) and Sheehan's syndrome; autoimmune hepatitis, lymphoid interstitial pneumonitis (HIV), bronchiolitis obliterans (non-transplant), non-specific interstitial pneumonia (NSIP), Guillain-BarreSyndrome, large vessel vasculitis (including polymyalgia rheumatica and giant cell (Takayasu's) arteritis), medium vessel vasculitis (including Kawasaki's disease and polyarteritis nodosa), polyarteritis nodosa (PAN) ankylosing spondylitis, Berger's disease (IgA nephropathy), rapidly progressive glomerulonephritis, primary biliary cirrhosis, Celiac sprue (gluten enteropathy), cryoglobulinemia, cryoglobulinemia associated with hepatitis, amyotrophic lateral sclerosis (ALS), coronary artery disease, familial Mediterranean fever, microscopic polyangiitis, Cogan's syndrome, Whiskott-Aldrich syndrome and thromboangiitis obliterans. In certain embodiments, in the context of treating an inflammatory disease, it may be preferable to design a CER with a homeostatic (non-inflammatory) engulfment signaling domain.

[0321] Infectious diseases include those associated with infectious agents and include any of a variety of bacteria (e.g., pathogenic E. coli, S. typhimurium, P. aeruginosa, B. anthracis, C. botulinum, C. difficile, C. perfringens, H. pylori, V. cholerae, Listeria spp., Rickettsia spp., Chlamydia spp., and the like), mycobacteria, and parasites (including any known parasitic member of the Protozoa). Infectious viruses include eukaryotic viruses, such as adenovirus, bunyavirus, herpesvirus, papovavirus, papillomavirus (e.g., HPV), paramyxovirus, picornavirus, rhabdovirus (e.g., Rabies), orthomyxovirus (e.g., influenza), poxvirus (e.g., Vaccinia), reovirus, retrovirus, lentivirus (e.g., HIV), flavivirus (e.g., HCV, HBV) or the like. In certain embodiments, a composition comprising a CER according to the present disclosure is used for treating infection with a microbe capable of establishing a persistent infection in a subject.

[0322] Neurodegenerative diseases include Lewy body disease, postpoliomyelitis syndrome, Shy-Draeger syndrome, olivopontocerebellar atrophy, Parkinson's disease, multiple system atrophy, striatonigral degeneration, frontotemporal lobar degeneration with ubiquitinated inclusions (FLTD-U), tauopathies (including, but not limited to, Alzheimer disease and supranuclear palsy), prion diseases (also known as transmissible spongiform encephalopathies, including, but not limited to, bovine spongiform encephalopathy, scrapie, Creutz-feldt-Jakob syndrome, kuru, Gerstmann-Straussler-Scheinker disease, chronic wasting disease, and fatal familial insomnia), bulbar palsy, motor neuron disease (including Amyotrophic lateral sclerosis (Lou Gherig's disease)), and nervous system heterodegenerative disorders (including, but not limited to, Canavan disease, Huntington's disease, neuronal ceroid-lipofuscinosis, Alexander's disease, Tourette's syndrome, Menkes kinky hair syndrome, Cockayne syndrome, Halervorden-Spatz syndrome, lafora disease, Rett syndrome, hepatolenticular degeneration, Lesch-Nyhan syndrome, and Unverricht-Lundborg syndrome), dementia (including, but not limited to, Pick's disease, and spinocerebellar ataxia), cancer (e.g., of the CNS and/or brain, including brain metastases resulting from cancer elsewhere in the body). Many neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis (Lou Gehrig's disease) and prion diseases, share a neuropathological signature, the aberrant accumulation of proteins, such as amyloid-.beta. or tau in Alzheimer's disease; .alpha.-synuclein in Parkinson's disease (PD), dementia with Lewy bodies, multiple system atrophy, or Alzheimer's disease; huntingtin in Huntington's disease, SODI in Amyotrophic lateral sclerosis, proteins with polyglutamine (polyQ) repeats in Huntington's disease or Amyotrophic lateral sclerosis; TDP-43 in Amyotrophic lateral sclerosis or FLTD-U; or prion protein (e.g., PrP.sup.SC) in prion diseases. Thus, in certain embodiments, CER therapy may be designed to target the disease-associated protein in order to reduce or prevent aberrant protein accumulation, thereby slowing or preventing progression of the neurodegenerative disease.

[0323] A CER of this disclosure may be administered to a subject in cell-bound form (e.g., gene therapy of target cell population (mature T cells (e.g., CD8.sup.+ or CD4.sup.+ T cells) or other cells of T cell lineage)). Thus, for example, a CER of the present disclosure may be administered to a subject expressed on the surface of T cells, Natural Killer Cells, Natural Killer T cells, B cells, lymphoid precursor cells, antigen presenting cells, dendritic cells, Langerhans cells, myeloid precursor cells, mature myeloid cells, including subsets thereof, or any combination thereof. In certain embodiments, methods of treating a patient include administering an effective amount of CER modified cells (i.e., recombinant cells that express one or more CERs). In such embodiments, the CER modified cells are xenogeneic, syngeneic, allogeneic, or autologous cells of T cell lineage, Natural Killer cell lineage, Natural Killer T cell lineage, B cell lineage, lymphoid precursor cell lineage, dendritic cell lineage, Langerhans cell lineage, myeloid cell lineage, or any combination thereof.

[0324] Pharmaceutical compositions including a CER modified cells may be administered in a manner appropriate to the disease or condition to be treated (or prevented) as determined by persons skilled in the medical art. An appropriate dose, suitable duration, and frequency of administration of the compositions will be determined by such factors as the condition of the patient, size, weight, body surface area, age, sex, type and severity of the disease, particular therapy to be administered, particular form of the active ingredient, time and the method of administration, and other drugs being administered concurrently. The present disclosure provides pharmaceutical compositions comprising CER modified cells and a pharmaceutically acceptable carrier, diluent, or excipient. Suitable excipients include water, saline, dextrose, glycerol, or the like and combinations thereof. Other suitable infusion medium can be any isotonic medium formulation, including saline, Normosol R (Abbott), Plasma-Lyte A (Baxter), 5% dextrose in water, or Ringer's lactate.

[0325] A treatment effective amount of cells in a pharmaceutical composition is at least one cell (for example, one CER modified B cell) or is more typically greater than 10.sup.2 cells, for example, up to 10.sup.6, up to 10.sup.7, up to 10.sup.8 cells, up to 10.sup.9 cells, up to 10.sup.10 cells, or up to 10.sup.1 cells or more. In certain embodiments, the cells are administered in a range from about 10.sup.6 to about 10.sup.10 cells/m.sup.2, preferably in a range of about 10.sup.7 to about 10.sup.9 cells/m.sup.2. The number of cells will depend upon the ultimate use for which the composition is intended as well the type of cells included therein. For example, a composition comprising cells modified to contain a CER specific for a particular antigen will comprise a cell population containing from about 5% to about 95% or more of such cells. In certain embodiments, a composition comprising CER modified cells comprises a cell population comprising at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or more of such cells. For uses provided herein, the cells are generally in a volume of a liter or less, 500 mls or less, 250 mls or less, or 100 mls or less. Hence the density of the desired cells is typically greater than 10.sup.4 cells/ml and generally is greater than 10.sup.7 cells/ml, generally 10.sup.8 cells/ml or greater. The cells may be administered as a single infusion or in multiple infusions over a range of time. Repeated infusions of CER modified cells may be separated by days, weeks, months, or even years if relapses of disease or disease activity are present. A clinically relevant number of immune cells can be apportioned into multiple infusions that cumulatively equal or exceed 10.sup.6, 10.sup.7, 10.sup.8, 10.sup.9, 10.sup.10, or 10.sup.11 cells. A preferred dose for administration of a host cell comprising a recombinant expression vector as described herein is about 10.sup.7 cells/m.sup.2, about 5.times.10.sup.7 cells/m.sup.2, about 10.sup.8 cells/m.sup.2, about 5.times.10.sup.8 cells/m.sup.2, about 10.sup.9 cells/m.sup.2, about 5.times.10.sup.9 cells/m.sup.2, about 10.sup.10 cells/m.sup.2, about 5.times.10.sup.10 cells/m.sup.2, or about 10.sup.11 cells/m.sup.2. In certain embodiments, a composition of CER modified B cells and a composition of CER modified T cells are both administered, which administration may be simultaneous, concurrent or sequential.

[0326] In some embodiments, a composition as described herein is administered intravenously, intraperitoneally, intratumoraly, into the bone marrow, into the lymph node, and/or into cerebrospinal fluid. In some embodiments, chimeric engulfment receptor engineered compositions are delivered to the site of the tumor.

[0327] In some embodiments, CER modified cells are administered to a subject in conjunction or combination with one or more additional therapies. In such embodiments, the one or more additional therapies may be one or more of radiation therapy, genetically engineered cellular immunotherapy (e.g., T cell, dendritic cell, natural killer cell, macrophage, chimeric antigen receptor (CAR) therapy), antibody therapy, immune checkpoint molecule inhibitor therapy, or a pharmaceutical therapy, such as a chemotherapeutic, a therapeutic peptide, antibiotic, anti-viral agent, anti-fungal agent, anti-inflammatory agent, or a small molecule therapy. In such embodiments, the CER modified cells may clear apoptotic, dead, dying, damaged, infected, or necrotic cells displaying pro-apoptotic markers induced in the setting of the one or more additional therapies. In certain embodiments where CER modified cells are administered in combination with one or more additional therapies, the one or more additional therapies may be administered at a subtherapeutic dose due to an additive or synergistic effect of the combination with CER therapy. Combination therapy includes administration of a CER before an additional therapy (e.g., 1 day to 30 days or more before the additional therapy), concurrently with an additional therapy (on the same day), or after an additional therapy (e.g., 1 day-30 days or more after the additional therapy). In certain embodiments, the CER modified cells are administered after administration of the one or more additional therapies. In further embodiments, the CER modified cells are administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days after administration of the one or more additional therapies. In still further embodiments, the CER modified cells are administered within 4 weeks, within 3 weeks, within 2 weeks, or within 1 week after administration of the one or more additional therapies. Where the one or more additional therapies involves multiple doses, the CER modified cells may be administered after the initial dose of the one or more additional therapies, after the final dose of the one or more additional therapies, or in between multiple doses of the one or more additional therapies.

[0328] An example of a triple combination therapy (radiation+CER+CAR/or TCR) regimen is shown in FIG. 134. Following radiation therapy, tumor antigen specific, CER modified host cells (e.g., comprising a binding domain that binds to a tumor antigen) according to the present disclosure are administered to a subject to promote an anti-tumor immune response and recruit immune activating cells into the tumor microenvironment. In certain embodiments, CERs traffic to local, irradiated tumors and render the tumor tissue permissive for immune infiltration and destruction (e.g., via expression of inflammatory cytokines, activation of effector T cells, activation of dendritic cells, inhibition of regulatory T cells), thereby sensitizing the tumor microenvironment for subsequent adoptive T cell immunotherapy (e.g., CAR or TCR immunotherapy). In certain embodiments, the CER modified cells are administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days after administration of the radiation therapy. In further embodiments, the CER modified cells are administered within 4 weeks, within 3 weeks, within 2 weeks, or within 1 week after administration of the radiation therapy. In certain embodiments, the CAR or TCR immunotherapy is administered 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days after administration of the CER therapy or within 4 weeks, within 3 weeks, within 2 weeks, or within 1 week after administration of the CER therapy. In certain embodiments, the radiation therapy, the CAR or TCR immunotherapy, or both are administered at subtherapeutic levels.

[0329] Examples of radiation therapy that may be used in combination with CER therapy include external beam radiation therapy (e.g., conventional external beam radiation therapy, stereotactic radiation, 3-dimensional conformal radiation therapy, intensity-modulated radiation therapy, volumetric modulated arc therapy, particle therapy, proton therapy, and auger therapy), brachytherapy, systemic radioisotope therapy, intraoperative radiotherapy, or any combination thereof.

[0330] Examples of immune checkpoint molecules that may be targeted in combination with CER therapy include PD-L1, PD-L2, CD80, CD86, B7-H3, B7-H4, HVEM, adenosine, GAL9, VISTA, CEACAM-1, CEACAM-3, CEACAM-5, PVRL2, PD-1, CTLA-4, BTLA, KIR, LAG3, TIM3, A2aR, CD244/2B4, CD160, TIGIT, LAIR-1, PVRIG/CD112R, or any combination thereof. In certain embodiments, an immune checkpoint molecule inhibitor is an antibody, a peptide, an RNAi agent, or a small molecule. An antibody specific for CTLA-4 may be ipilimumab or tremelimumab. An antibody specific for PD-1 may be pidilizumab, nivolumab, or pembrolizumab. An antibody specific for PD-L1 may be durvalumab, atezolizumab, or avelumab.

[0331] Exemplary chemotherapeutics include an alkylating agent, a platinum based agent, an angiogenesis inhibitor (e.g., a VEGF pathway inhibitor), a tyrosine kinase inhibitor (e.g., an EGF pathway inhibitor), a B-Raf inhibitor, a MEK inhibitor, an mTOR inhibitor, a cytotoxic agent, an inhibitor of chromatin function, a topoisomerase inhibitor, a microtubule inhibiting drug, a DNA damaging agent, an antimetabolite (such as folate antagonists, pyrimidine analogs, purine analogs, and sugar-modified analogs), a DNA synthesis inhibitor, a DNA interactive agent (such as an intercalating agent), and a DNA repair inhibitor.

[0332] Examples of chemotherapeutic agents considered for use in combination therapies include vemurafenib, dabrafenib, trametinib, cobimetinib, anastrozole (Arimidex.RTM.), bicalutamide (Casodex.RTM.), bleomycin sulfate (Blenoxane.RTM.), busulfan (Myleran.RTM.), busulfan injection (Busulfex.RTM.), capecitabine (Xeloda.RTM.), N4-pentoxycarbonyl-5-deoxy-5-fluorocytidine, carboplatin (Paraplatin.RTM.), carmustine (BiCNU.RTM.), chlorambucil (Leukeran.RTM.), cisplatin (Platinol.RTM.), cladribine (Leustatin.RTM.), cyclophosphamide (Cytoxan.RTM. or Neosar.RTM.), cytarabine, cytosine arabinoside (Cytosar-U.RTM.), cytarabine liposome injection (DepoCyt.RTM.), dacarbazine (DTIC-Dome.RTM.), dactinomycin (Actinomycin D, Cosmegan), daunorubicin hydrochloride (Cerubidine.RTM.), daunorubicin citrate liposome injection (DaunoXome.RTM.), dexamethasone, docetaxel (Taxotere.RTM.), doxorubicin hydrochloride (Adriamycin.RTM., Rubex.RTM.), etoposide (Vepesid.RTM.), fludarabine phosphate (Fludara.RTM.), 5-fluorouracil (Adrucil.RTM., Efudex.RTM.), flutamide (Eulexin.RTM.), tezacitibine, Gemcitabine (difluorodeoxycitidine), hydroxyurea (Hydrea.RTM.), Idarubicin (Idamycin.RTM.), ifosfamide (IFEX.RTM.), irinotecan (Camptosar.RTM.), L-asparaginase (ELSPAR.RTM.), leucovorin calcium, melphalan (Alkeran.RTM.), 6-mercaptopurine (Purinethol.RTM.), methotrexate (Folex.RTM.), mitoxantrone (Novantrone.RTM.), mylotarg, paclitaxel (Taxol.RTM.), phoenix (Yttrium90/MX-DTPA), pentostatin, polifeprosan 20 with carmustine implant (Gliadel.RTM.), tamoxifen citrate (Nolvadex.RTM.), teniposide (Vumon.RTM.), 6-thioguanine, thiotepa, tirapazamine (Tirazone.RTM.), topotecan hydrochloride for injection (Hycamptin.RTM.), vinblastine (Velban.RTM.), vincristine (Oncovin.RTM.), and vinorelbine (Navelbine.RTM.).

[0333] Exemplary alkylating agents include nitrogen mustards, ethylenimine derivatives, alkyl sulfonates, nitrosoureas and triazenes): uracil mustard (Aminouracil Mustard.RTM., Chlorethaminacil.RTM., Demethyldopan.RTM., Desmethyldopan.RTM., Haemanthamine.RTM., Nordopan.RTM., Uracil nitrogen Mustard.RTM., Uracillost.RTM., Uracilmostaza.RTM., Uramustin.RTM., Uramustine.RTM.), chlormethine (Mustargen.RTM.), cyclophosphamide (Cytoxan.RTM., Neosar.RTM., Clafen.RTM., Endoxan.RTM., Procytox.RTM., Revimmune.TM.), ifosfamide (Mitoxana.RTM.), melphalan (Alkeran.RTM.), Chlorambucil (Leukeran.RTM.), pipobroman (Amedel.RTM., Vercyte.RTM.), triethylenemelamine (Hemel.RTM., Hexalen.RTM., Hexastat.RTM.), triethylenethiophosphoramine, Temozolomide (Temodar.RTM.), thiotepa (Thioplex.RTM.), busulfan (Busilvex.RTM., Myleran.RTM.), carmustine (BiCNU.RTM.), lomustine (CeeNU.RTM.), streptozocin (Zanosar.RTM.), and Dacarbazine (DTIC-Dome.RTM.). Additional exemplary alkylating agents include, without limitation, Oxaliplatin (Eloxatin.RTM.); Temozolomide (Temodar.RTM. and Temodal.RTM.); Dactinomycin (also known as actinomycin-D, Cosmegen.RTM.); Melphalan (also known as L-PAM, L-sarcolysin, and phenylalanine mustard, Alkeran.RTM.); Altretamine (also known as hexamethylmelamine (HMM), Hexalen.RTM.); Carmustine (BiCNU.RTM.); Bendamustine (Treanda.RTM.); Busulfan (Busulfex.RTM. and Myleran.RTM.); Carboplatin (Paraplatin.RTM.); Lomustine (also known as CCNU, CeeNU.RTM.); Cisplatin (also known as CDDP, Platinol.RTM. and Platinol.RTM.-AQ); Chlorambucil (Leukeran.RTM.); Cyclophosphamide (Cytoxan.RTM. and Neosar.RTM.); Dacarbazine (also known as DTIC, DIC and imidazole carboxamide, DTIC-Dome.RTM.); Altretamine (also known as hexamethylmelamine (HMM), Hexalen.RTM.); Ifosfamide (Ifex.RTM.); Prednumustine; Procarbazine (Matulane.RTM.); Mechlorethamine (also known as nitrogen mustard, mustine and mechloroethamine hydrochloride, Mustargen.RTM.); Streptozocin (Zanosar.RTM.); Thiotepa (also known as thiophosphoamide, TESPA and TSPA, Thioplex.RTM.); Cyclophosphamide (Endoxan.RTM., Cytoxan.RTM., Neosar.RTM., Procytox.RTM., Revimmune.RTM.); and Bendamustine HCl (Treanda.RTM.).

[0334] Exemplary platinum based agents include carboplatin, cisplatin, oxaliplatin, nedaplatin, picoplatin, satraplatin, phenanthriplatin, and triplatin tetranitrate.

[0335] Exemplary angiogenesis inhibitors include, without limitation A6 (Angstrom Pharmaceuticals), ABT-510 (Abbott Laboratories), ABT-627 (Atrasentan) (Abbott Laboratories/Xinlay), ABT-869 (Abbott Laboratories), Actimid (CC4047, Pomalidomide) (Celgene Corporation), AdGVPEDF.11D (GenVec), ADH-1 (Exherin) (Adherex Technologies), AEE788 (Novartis), AG-013736 (Axitinib) (Pfizer), AG3340 (Prinomastat) (Agouron Pharmaceuticals), AGX1053 (AngioGenex), AGX51 (AngioGenex), ALN-VSP (ALN-VSP 02) (Alnylam Pharmaceuticals), AMG 386 (Amgen), AMG706 (Amgen), Apatinib (YN968D1) (Jiangsu Hengrui Medicine), AP23573 (Ridaforolimus/MK8669) (Ariad Pharmaceuticals), AQ4N (Novavea), ARQ 197 (ArQule), ASA404 (Novartis/Antisoma), Atiprimod (Callisto Pharmaceuticals), ATN-161 (Attenuon), AV-412 (Aveo Pharmaceuticals), AV-951 (Aveo Pharmaceuticals), Avastin (Bevacizumab) (Genentech), AZD2171 (Cediranib/Recentin) (AstraZeneca), BAY 57-9352 (Telatinib) (Bayer), BEZ235 (Novartis), BIBF1120 (Boehringer Ingelheim Pharmaceuticals), BIBW 2992 (Boehringer Ingelheim Pharmaceuticals), BMS-275291 (Bristol-Myers Squibb), BMS-582664 (Brivanib) (Bristol-Myers Squibb), BMS-690514 (Bristol-Myers Squibb), Calcitriol, CCI-779 (Torisel) (Wyeth), CDP-791 (ImClone Systems), Ceflatonin (Homoharringtonine/HHT) (ChemGenex Therapeutics), Celebrex (Celecoxib) (Pfizer), CEP-7055 (Cephalon/Sanofi), CHIR-265 (Chiron Corporation), NGR-TNF, COL-3 (Metastat) (Collagenex Pharaceuticals), Combretastatin (Oxigene), CP-751,871(Figitumumab) (Pfizer), CP-547,632 (Pfizer), CS-7017 (Daiichi Sankyo Pharma), CT-322 (Angiocept) (Adnexus), Curcumin, Dalteparin (Fragmin) (Pfizer), Disulfiram (Antabuse), E7820 (Eisai Limited), E7080 (Eisai Limited), EMD 121974(Cilengitide) (EMD Pharmaceuticals), ENMD-1198 (EntreMed), ENMD-2076 (EntreMed), Endostar (Simcere), Erbitux (ImClone/Bristol-Myers Squibb), EZN-2208 (Enzon Pharmaceuticals), EZN-2968 (Enzon Pharmaceuticals), GC1008 (Genzyme), Genistein, GSK 1363089(Foretinib) (GlaxoSmithKline), GW786034 (Pazopanib) (GlaxoSmithKline), GT-111 (Vascular Biogenics Ltd.), IMC-1121B (Ramucirumab) (ImClone Systems), IMC-18F1 (ImClone Systems), IMC-3G3 (ImClone LLC), INCB007839 (Incyte Corporation), INGN 241 (Introgen Therapeutics), Iressa (ZD1839/Gefitinib), LBH589 (Faridak/Panobinostst) (Novartis), Lucentis (Ranibizumab) (Genentech/Novartis), LY317615 (Enzastaurin) (Eli Lilly and Company), Macugen (Pegaptanib) (Pfizer), MEDI522 (Abegrin) (MedImmune), MLN518(Tandutinib) (Millennium), Neovastat (AE941/Benefin) (Aeterna Zentaris), Nexavar (Bayer/Onyx), NM-3 (Genzyme Corporation), Noscapine (Cougar Biotechnology), NPI-2358 (Nereus Pharmaceuticals), OSI-930 (OSI), Palomid 529 (Paloma Pharmaceuticals, Inc.), Panzem Capsules (2ME2) (EntreMed), Panzem NCD (2ME2) (EntreMed), PF-02341066 (Pfizer), PF-04554878 (Pfizer), PI-88 (Progen Industries/Medigen Biotechnology), PKC412 (Novartis), Polyphenon E (Green Tea Extract) (Polypheno E International, Inc), PPI-2458 (Praecis Pharmaceuticals), PTC299 (PTC Therapeutics), PTK787 (Vatalanib) (Novartis), PXD101 (Belinostat) (CuraGen Corporation), RAD001 (Everolimus) (Novartis), RAF265 (Novartis), Regorafenib (BAY73-4506) (Bayer), Revlimid (Celgene), Retaane (Alcon Research), SN38 (Liposomal) (Neopharm), SNS-032 (BMS-387032) (Sunesis), SOM230(Pasireotide) (Novartis), Squalamine (Genaera), Suramin, Sutent (Pfizer), Tarceva (Genentech), TB-403 (Thrombogenics), Tempostatin (Collard Biopharmaceuticals), Tetrathiomolybdate (Sigma-Aldrich), TG100801 (TargeGen), Thalidomide (Celgene Corporation), Tinzaparin Sodium, TKI258 (Novartis), TRC093 (Tracon Pharmaceuticals Inc.), VEGF Trap (Aflibercept) (Regeneron Pharmaceuticals), VEGF Trap-Eye (Regeneron Pharmaceuticals), Veglin (VasGene Therapeutics), Bortezomib (Millennium), XL184 (Exelixis), XL647 (Exelixis), XL784 (Exelixis), XL820 (Exelixis), XL999 (Exelixis), ZD6474 (AstraZeneca), Vorinostat (Merck), and ZSTK474.

[0336] Exemplary Vascular Endothelial Growth Factor (VEGF) receptor inhibitors include, but are not limited to, Bevacizumab (Avastin.RTM.), axitinib (Inlyta.RTM.); Brivanib alaninate (BMS-582664, (S)-((R)-1-(4-(4-Fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[2,1-f]- [1,2,4]triazin-6-yloxy)propan-2-yl)2-aminopropanoate); Sorafenib (Nexavar.RTM.); Pazopanib (Votrient.RTM.); Sunitinib malate (Sutent.RTM.); Cediranib (AZD2171, CAS 288383-20-1); Vargatef (BIBF1120, CAS 928326-83-4); Foretinib (GSK1363089); Telatinib (BAY57-9352, CAS 332012-40-5); Apatinib (YN968D1, CAS 811803-05-1); Imatinib (Gleevec.RTM.); Ponatinib (AP24534, CAS 943319-70-8); Tivozanib (AV951, CAS 475108-18-0); Regorafenib (BAY73-4506, CAS 755037-03-7); Vatalanib dihydrochloride (PTK787, CAS 212141-51-0); Brivanib (BMS-540215, CAS 649735-46-6); Vandetanib (Caprelsa.RTM. or AZD6474); Motesanib diphosphate (AMG706, CAS 857876-30-3, N-(2,3-dihydro-3,3-dimethyl-1H-indol-6-yl)-2-[(4-pyridinylmethyl)amino]-3- -pyridinecarboxamide, described in PCT Publication No. WO 02/066470); Dovitinib dilactic acid (TKI258, CAS 852433-84-2); Linfanib (ABT869, CAS 796967-16-3); Cabozantinib (XL184, CAS 849217-68-1); Lestaurtinib (CAS 111358-88-4); N-[5-[[[5-(1,1-Dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]-4-pipe- ridinecarboxamide (BMS38703, CAS 345627-80-7); (3R,4R)-4-Amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-f][1,2,4]triazi- n-5-yl)methyl)piperidin-3-ol (BMS690514); N-(3,4-Dichloro-2-fluorophenyl)-6-methoxy-7-[[(3aa,5.beta.,6aa)-octahydro- -2-methylcyclopenta[c]pyrrol-5-yl]methoxy]-4-quinazolinamine (XL647, CAS 781613-23-8); 4-Methyl-3-[[1-methyl-6-(3-pyridinyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]am- ino]-N-[3-(trifluoromethyl)phenyl]-benzamide (BHG712, CAS 940310-85-0); and Aflibercept (Eylea.RTM.).

[0337] Exemplary EGF pathway inhibitors include, without limitation tyrphostin 46, EKB-569, erlotinib (Tarceva.RTM.), gefitinib (Iressa.RTM.), erbitux, nimotuzumab, lapatinib (Tykerb.RTM.), cetuximab (anti-EGFR mAb), l8Re-labeled nimotuzumab (anti-EGFR mAb), and those compounds that are generically and specifically disclosed in WO 97/02266, EP 0 564 409, WO 99/03854, EP 0 520 722, EP 0 566 226, EP 0 787 722, EP 0 837 063, U.S. Pat. No. 5,747,498, WO 98/10767, WO 97/30034, WO 97/49688, WO 97/38983 and WO 96/33980. Exemplary EGFR antibodies include, but are not limited to, Cetuximab (Erbitux.RTM.); Panitumumab (Vectibix.RTM.); Matuzumab (EMD-72000); Trastuzumab (Herceptin.RTM.); Nimotuzumab (hR3); Zalutumumab; TheraCIM h-R3; MDX0447 (CAS 339151-96-1); and ch806 (mAb-806, CAS 946414-09-1). Exemplary Epidermal growth factor receptor (EGFR) inhibitors include, but not limited to, Erlotinib hydrochloride (Tarceva.RTM.), Gefitnib (Iressa.RTM.); N-[4-[(3-Chloro-4-fluorophenyl)amino]-7-[[(3''S'')-tetrahydro-3-furanyl]o- xy]-6-quinazolinyl]-4(dimethylamino)-2-butenamide, Tovok.RTM.); Vandetanib (Caprelsa.RTM.); Lapatinib (Tykerb.RTM.); (3R,4R)-4-Amino-1-((4-((3-methoxyphenyl)amino)pyrrolo[2,1-f][1,2,4]triazi- n-5-yl)methyl)piperidin-3-ol (BMS690514); Canertinib dihydrochloride (CI-1033); 6-[4-[(4-Ethyl-1-piperazinyl)methyl]phenyl]-N-[(1R)-1-phenylethyl]-7H-Pyr- rolo[2,3-d]pyrimidin-4-amine (AEE788, CAS 497839-62-0); Mubritinib (TAK165); Pelitinib (EKB569); Afatinib (BIBW2992); Neratinib (HKI-272); N-[4-[[1-[(3-Fluorophenyl)methyl]-1H-indazol-5-yl]amino]-5-methylpyrrolo[- 2,1-f][1,2,4]triazin-6-yl]-carbamic acid, (3S)-3-morpholinylmethyl ester (BMS599626); N-(3,4-Dichloro-2-fluorophenyl)-6-methoxy-7-[[(3 a.alpha.,5.beta.,6a.alpha.)-octahydro-2-methylcyclopenta[c]pyrrol-5-yl]me- thoxy]-4-quinazolinamine (XL647, CAS 781613-23-8); and 4-[4-[[(1R)-1-Phenylethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-6-yl]-phenol (PKI166, CAS 187724-61-4).

[0338] Exemplary mTOR inhibitors include, without limitation, rapamycin (Rapamune.RTM.), and analogs and derivatives thereof; SDZ-RAD; Temsirolimus (Torisel.RTM.; also known as CCI-779); Ridaforolimus (formally known as deferolimus, (1R,2R,4S)-4-[(2R)-2[(1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28Z,30S,3- 2S,35R)-1,18-dihydroxy-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-2,3,10- ,14,20-pentaoxo-11,36-dioxa-4-azatricyclo[30.3.1.0.sup.4,9]hexatriaconta-1- 6,24,26,28-tetraen-12-yl]propyl]-2-methoxycyclohexyl dimethylphosphinate, also known as AP23573 and MK8669, and described in PCT Publication No. WO 03/064383); Everolimus (Afinitor.RTM. or RAD001); Rapamycin (AY22989, Sirolimus.RTM.); Simapimod (CAS 164301-51-3); (5-{2,4-Bis[(3 S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl}-2-methoxyphenyl)me- thanol (AZD8055); 2-Amino-8-[trans-4-(2-hydroxyethoxy)cyclohexyl]-6-(6-methoxy-3-pyridinyl)- -4-methyl-pyrido[2,3-d]pyrimidin-7(8H)-one (PF04691502, CAS 1013101-36-4); and N.sup.2-[1,4-dioxo-[[4-(4-oxo-8-phenyl-4H-1-benzopyran-2-yl)morpholin- ium-4-yl]methoxy]butyl]-L-arginylglycyl-L-.alpha.-aspartylL-serine-, inner salt (SF1126, CAS 936487-67-1).

[0339] Exemplary Phosphoinositide 3-kinase (PI3K) inhibitors include, but are not limited to, 4-[2-(1H-Indazol-4-yl)-6-[[4-(methylsulfonyl)piperazin-1-yl]methyl]thieno- [3,2-d]pyrimidin-4-yl]morpholine (also known as GDC 0941 and described in PCT Publication Nos. WO 09/036082 and WO 09/055730); 2-Methyl-2-[4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydroimidazo[4,5-c]- quinolin-1-yl]phenyl]propionitrile (also known as BEZ 235 or NVP-BEZ 235, and described in PCT Publication No. WO 06/122806); 4-(trifluoromethyl)-5-(2,6-dimorpholinopyrimidin-4-yl)pyridin-2-amine (also known as BKM120 or NVP-BKM120, and described in PCT Publication No. WO2007/084786); Tozasertib (VX680 or MK-0457, CAS 639089-54-6); (5Z)-5-[[4-(4-Pyridinyl)-6-quinolinyl]methylene]-2,4-thiazolidinedione (GSK1059615, CAS 958852-01-2); (1E,4S,4aR,5R,6aS,9aR)-5-(Acetyloxy)-1-[(di-2-propenylamino)methylene]-4,- 4a,5,6,6a,8,9,9a-octahydro-11-hydroxy-4-(methoxymethyl)-4a,6a-dimethyl-cyc- lopenta[5,6]naphtho[1,2-c]pyran-2,7,10(1H)-trione (PX866, CAS 502632-66-8); and 8-Phenyl-2-(morpholin-4-yl)-chromen-4-one (LY294002, CAS 154447-36-6). Exemplary Protein Kinase B (PKB) or AKT inhibitors include, but are not limited to. 8-[4-(1-Aminocyclobutyl)phenyl]-9-phenyl-1,2,4-triazolo[3,4-f][1,6]naphth- yridin-3(2H)-one (MK-2206, CAS 1032349-93-1); Perifosine (KRX0401); 4-Dodecyl-N-1,3,4-thiadiazol-2-yl-benzenesulfonamide (PHT-427, CAS 1191951-57-1); 4-[2-(4-Amino-1,2,5-oxadiazol-3-yl)-1-ethyl-7-[(3S)-3-piperidinylmethoxy]- -1H-imidazo[4,5-c]pyridin-4-yl]-2-methyl-3-butyn-2-ol (GSK690693, CAS 937174-76-0); 8-(1-Hydroxyethyl)-2-methoxy-3-[(4-methoxyphenyl)methoxy]-6H-dibenzo[b,d]- pyran-6-one (palomid 529, P529, or SG-00529); Tricirbine (6-Amino-4-methyl-8-(j3-D-ribofuranosyl)-4H,8H-pyrrolo[4,3,2-de]pyrimido[- 4,5-c]pyridazine); (.alpha.S)-.alpha.-[[[5-(3-Methyl-1H-indazol-5-yl)-3-pyridinyl]oxy]methyl- ]-benzeneethanamine (A674563, CAS 552325-73-2); 4-[(4-Chlorophenyl)methyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4-piperidi- namine (CCT128930, CAS 885499-61-6); 4-(4-Chlorophenyl)-4-[4-(1H pyrazol-4-yl)phenyl]-piperidine (AT7867, CAS 857531-00-1); and Archexin (RX-0201, CAS 663232-27-7).

[0340] FIGS. 5A-5C, 93, and 94 illustrate embodiments of regimens that utilize CER modified cells. As shown in FIG. 5A, following leukapheresis, cells can be processed and activated ex vivo, undergoing genetic modification and expansion in preparation for infusion into a subject. FIG. 5B shows an illustrative treatment scheme for CER-modified cells used in combination with conventional T cell based therapies. An initial infusion of engineered T cells induces tumor cell apoptosis indicative of an anti-tumor effect. CER modified cells are then infused. The CER modified cells clear tumor cells displaying a pro-engulfment (e.g., PtdSer), which facilitates tumor regression while also bypassing the T cell suppressive tumor microenvironment. Alteration of the tumor microenvironment then re-sensitizes the tumor to T cell therapy, allowing a second infusion of T cells. Another embodiment of a therapeutic method is shown in FIG. 5C. The treatment scheme shown in FIG. 5C utilizes CER modified cells in combination with a monoclonal antibody therapy. Infusion of tumor-specific antibodies, such as Cetuximab targeting EGFR or Rituximab targeting CD20 may trigger cell death or induce a targeting moiety that is bound by CER modified cells. Subsequently, a subject receives CER modified cells that bind to and clear antibody bound cells. In such an embodiment, the CER extracellular domain may include an FcR binding domain, a PtdSer binding domain, or other antigen binding domain.

[0341] In another scenario, a CER modified cell can be combined with small molecule inhibitors such as a BTK inhibitor, a MEK inhibitor, an adenosine pathway inhibitor A2AR antagonist, an IDO1 inhibitor, IMiDs such as Lenalidomide, PI3K.delta. inhibitors, a BRAF inhibitor, or a BCR-ABL inhibitor.

[0342] In certain embodiments, methods of the present disclosure include a depletion step. A depletion step to remove CERs from the subject may occur after a sufficient amount of time for therapeutic benefit in order to mitigate toxicity to a subject. In such embodiments, the CER vector includes an inducible suicide gene, such as iCASP9, inducible Fas, or HSV-TK. Similarly, a CER vector may be designed for expression of a known cell surface antigen such as CD20 or truncated EGFR (SEQ ID NO: 121) that facilitates depletion of transduced cells through infusion of an associated monoclonal antibody (mAb), for example, Rituximab for CD20 or Cetuximab for EGFR. Alemtuzumab, which targets CD52 present on the surface of mature lymphocytes, may also be used to deplete transduced B cells, T cells, or natural killer cells.

[0343] In further embodiments, cells expressing CER of the instant disclosure may be used in diagnostic methods or imaging methods, including methods used in relation to the indications or conditions identified herein.

EXAMPLES

Example 1

[0344] CREATION OF CER CONSTRUCTS The expression of natural or synthetic nucleic acid molecules encoding CERs is achieved by operably linking a nucleic acid molecule encoding the CER protein or portions thereof to a promoter, and incorporating the construct into an expression vector suitable for replication and integration eukaryotes. The vector contains transcription and translation terminators, an initiation sequence, and a promoter useful for regulation of the expression of the desired nucleic acid sequence.

[0345] In order to assess the expression of a CER protein or portions thereof, the expression vector to be introduced into a cell contains a selectable marker gene, such as an antibiotic resistance gene, or a reporter gene to facilitate identification and selection of expressing cells from the population of cells sought to be transfected or infected through viral vectors. The selectable marker is carried on a separate piece of DNA and used in a co-transfection procedure. The selectable marker or reporter gene is flanked with appropriate regulatory sequences to enable expression in the host cells. The expression vector is transferred into a host cell by way of a retroviral vector. In order to confirm the presence of the recombinant DNA sequence in the host cell, a variety of assays are performed including RT-PCR and ELISA.

[0346] EVALUATION OF CER PERFORMANCE To identify and characterize CERs, an in vitro system that reconstitutes phagocytic cell engulfment using retroviral-mediated transduction of candidate CER has been established. Murine and human lymphocyte cell lines, which normally lack the capacity to engulf cells, are transduced with CERs to assess for gain of function activity. If a CER is successfully expressed, engulfment occurs in heterologous cells. In addition to their engulfment activity, CERs are evaluated for their capacity to: (1) polarize cells to release inflammatory cytokines and chemokines; (2) activate downstream proliferative pathways and; (3) render target cells with a non-therapy-induced resistance pattern. In order to evaluate the candidate CERs, multi-dimensional flow cytometry, cytokine/chemokine arrays, and functional assays (below) are used.

Example 2

[0347] IN VITRO PHAGOCYTOSIS The mouse pro-B cell line Ba/F3 or human Jurkat T cells lack intrinsic phagocytic capacity to phagocytose apoptotic or tumor cells in vitro and are used as an initial screening cell line to identify lead CER candidates. Following CER Retroviral transduction, Ba/F3 or Jurkat T cells are purified, labeled, and immunophenotypically characterized. Phagocytic activity is measured using in vitro co-culture experiments with defined target cells under various co-culture conditions and engulfment measured by FACs or light emission microscopy. Ba/F3 or Jurkat T cell-transduced CER cells with extracellular PtdSer targeting domains are co-cultured with pHrodo-labeled apoptotic cells. This assay permits evaluation of phagocytosis of apoptotic cells entering cytosolic lysosomes. In other cases, Ba/F3 or Jurkat T cell-transduced CER cells with Fc receptor extracellular domains are co-incubated with target cells pre-incubated with an antibody, such as a tumor specific antibody, to measure the capacity of these cells to phagocytose antibody-coated tumor cells. Finally, Ba/F3 or Jurkat T cell-transduced CERs that bind to tumor antigens through antibody binding moieties, such as a single-chain variable fragment, are co-cultured with tumor cells, and phagocytosis quantified. In some cases, target cells are pre-treated with conventional chemotherapy, radiation, or small molecule therapy, prior to co-culture experiments, to induce a `pro-phagocytic` molecular state. Phagocytic activity is quantified as the percentage of Cell Tracker-positive cells in labeled Ba/F3 Jurkat transformants after a 90 minute co-culture experiment.

Cytokine/Chemokine Array Analysis from Conditioned Media

[0348] In parallel, conditioned media is collected from Ba/F3 or Jurkat T cell transformant co-culture experiments and analyzed for release of inflammatory cytokines/chemokines assays. Cytokines/chemokine changes before and after Ba/F3 Jurkat transduction and relative comparisons are quantified to evaluate for gain of functionality. CER candidates that polarize cells to an inflammatory state by both (i) down-regulating immunosuppressive cytokines, such as IL-10 and TGF-.beta., monocyte chemo attractants involved in recruitment of immature monocytes and myeloid-derived suppressive cells, and (ii) upregulating inflammatory cytokines TNF alpha, IL12p70, IFN.alpha., and IFN.gamma. are identified.

[0349] MULTI-DIMENSIONAL FLOW CYTOMETRY Ba/F3 and Jurkat transformants are analyzed in parallel using multi-dimensional cytometry to characterize activation and inhibitory receptor profiles. An activation profile may include CD137, CD69, HLA-DR, CD107a, CD123, CD11c, TNF, IFN.gamma., IL-2, Granzyme, Perforin, CD25, CD40L, CD80, and CD86, while an inhibitory profile may include PD-1, Tim-3, Lag-3, ICOS, and CD172a. Bystander cells within culture are immunophenotypically evaluated for therapy-induced resistance patterns.

[0350] PROLIFERATIVE ASSAYS Primary human T cells transduced with CER cassettes are analyzed for constitutive or non-constitutive growth patterns in the presence or absence of exogenous cytokines or feeder cells.

[0351] DOWNSTREAM PRO-INFLAMMATORY SIGNALING PATHWAYS To further test downstream pro-inflammatory responses, phospho-CYTOF are performed to measure downstream signaling pathways activated by candidate CERs such as, IkBtot, pSTAT1, p38, and JNK.

Example 3

[0352] IN VIVO ANALYSIS To test CER modified cells in vivo, animal models and ex vivo experiments are used. Human primary tumor cell or xenograft specimens are engrafted into Nod/SCD.gamma. mice. Expansion and persistence of modified CER cells can be quantified using primers specific to the CER cassette with a droplet PCR (ddPCR) machine from blood and tissue specimens. To analyze the functional capacity of CER cells ex vivo, tumor tissues and splenocytes are processed and analyzed by FACS and tissue staining for phenotyping and demonstration of in vivo phagocytosis after adoptive transfer of CER-modified cells. Tumor growth is monitored and quantified in vivo.

Example 4

Construction of Tim4-MERTK Chimeric Engulfment Receptor (CER) "CER01"

[0353] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (encoding amino acid sequence of SEQ ID NO:72) and transmembrane domain (encoding amino acid sequence of SEQ ID NO:74) (together having a polynucleotide sequence of SEQ ID NO: 57), were fused to the intracellular kinase domain of the tyrosine kinase MERTK (encoding SEQ ID NO: 58) to create a chimeric engulfment receptor "CER01" (Tim4-MERTK CER having an amino acid sequence of SEQ ID NO:71) (FIG. 6A). The MERTK receptor tyrosine kinase transduces a signal for engulfment, and Tim4 has recently been described as a phosphatidylserine binding receptor (Miyanishi et al., Nature, 2007, 450:435-9; Nishi et al., 2014, Mol. Cell Biol. 34:1512-20). The Tim-4-MERTK chimeric engulfment receptor nucleotide sequence was then inserted into the pMSCV (murine stem cell virus) retroviral vector. Early passage murine Ba/F3 B-cells were transduced with pMSCV Tim4-MERTK retrovirus expressing yellow fluorescent protein (GFP) as a transduction marker. Positive Ba/F3 cell transductants were sorted by GFP expression using flow cytometry (FACs), expanded in culture, and used for in vitro studies.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0354] Primary thymocytes were incubated with 10 .mu.M dexamethasone for 24 hours to induce cell death. Thymocytes were then labeled with 1 .mu.M of pHrodo Red dye in PBS for 15 minutes at room temperature, washed 2.times. with RPMI media containing 10% fetal bovine serum, and used as target cells for phagocytosis assays. 50 .mu.l of pHrodo Red-labeled thymocytes (10.sup.6/mL) were incubated with 50 .mu.l of Tim4-MERTK chimeric engulfment receptor expressing sorted Ba/F3 cells (10.sup.5/mL) (target cell to effector cell ratio of 10:1). Labeling target cells with pHrodo Red dye permits visualization of cells that are engulfed and transported into lysosomes due to their increased light emission in the acidic lysosomal environment (Miksa et al., 2009, Immunol. Methods 342:71-7). Co-culture experiments were carried out and Ba/F3 GFP+ cells were serially quantified for phagocytosis by fluorescence microscopy and FACs at 2 hr, 24 hr, 48 hr, and 72 hr post-incubation. Ba/F3 cells transduced with pMSCV vector expressing Tim4 and GFP (non-engulfment receptor) were used as a negative control.

[0355] Under normal conditions, the Ba/F3 murine B-cell line lacks the capacity to engulf target cells and was therefore selected to establish an assay system for engulfment. Tim4-MERTK CER-mediated engulfment of apoptotic thymocytes were first examined (FIGS. 6A-F). Expression of Tim4-MERTK CER in the murine Ba/F3 B-cell line strongly enhanced phagocytic uptake of phosphatidylserine positive (PtdSer.sup.+) thymocytes (FIGS. 6C-6F). Observation by fluorescent microscopy and FACs show that the amount of phagocytosis correlates with incubation time with target cells, as well as, the quantity of Tim4-MERTK CER expression (FIGS. 6C-6D). Two hours following co-incubation, 21.6% of Tim4-MERTK CER transduced Ba/F3 cells had engulfed target apoptotic thymocytes, compared to 0% in control groups (FIG. 6C). The number of phagocytic Ba/F3 cells expressing Tim4-MERTK CER increased to 57.5% at 24 hours incubation time, and 75% at 72 hours incubation time (FIGS. 6C-6D). Furthermore, Ba/F3 cells that expressed the highest amount of Tim4-MERTK CERs exhibited the greatest amount of phagocytosis, approaching 80% within the top expression quartile (FIG. 6D), indicating a concentration dependent effect of the Tim4-MERTK CER.

[0356] The ability of the Tim4-MERTK CER to facilitate transfer of ingested target cells into phagolysosomes was then examined. The lysosome, containing hydrolytic enzymes, digests ingested cells in a reduced pH internal environment (Arandjelovic et al., 2015, Nat. Immunol. 16:907-17). In this setting, pHrodo Red-labeled target thymocytes increase in fluorescent intensity. Observation by fluorescence microscopy showed several pHrodo Red-positive cells present inside most of Tim4-MERTK CER-expressing Ba/F3 cells (FIG. 6E). In full agreement with this observation, the entry of target cells into phagolysosomes of Tim4-MERTK CER-expressing Ba/F3 cells was associated with their clearance. By day 4, 97% of target cells had been eliminated through phagocytic uptake and lysosome degradation (FIGS. 7A-7B). These results indicate the addition of a Tim4-MERTK CER strongly enhances clearance of PtdSer.sup.+ cells.

[0357] To examine the capacity to CER-expressing cells to clear tumor cells, Tim4-MERTK CER-mediated engulfment of the Raji human Burkitt B-cell lymphoma cell line was tested (FIGS. 8A-8B). Studies indicate B-cell receptors (BCRs) incorporate PtdSer into membrane microdomains in anti-IgM-activated B-cells and in the setting of aberrant signaling activity, such as exists in constitutively active Raji lymphoma cells (Dillon et al., 2000, J. Immunol. 164:1322-32). Expression of Tim4-MERTK CER in the murine Ba/F3 B-cell line enhanced phagocytic uptake of Raji cells (FIGS. 8A-8C), indicating Tim4-MERTK CER-mediated anti-tumor effects.

Example 5

Construction of FA58C2-MERTK CER "CER03"

[0358] The phosphatidylserine binding motif FA58C2 from the macrophage opsonin MFGE8 (amino acid sequence of SEQ ID NO:30) was fused to a modified IgG4 extracellular spacer domain (amino acid sequence of SEQ ID NO:67) and the transmembrane domain of costimulatory molecule CD28 (amino acid sequence of SEQ ID NO:68), and the cytoplasmic kinase domain of MERTK (amino acid sequence of SEQ ID NO:43) to create the chimeric engulfment receptor "CER03" (FA58C2-MERTK CER) (polynucleotide sequence of SEQ ID NO: 59, amino acid sequence of SEQ ID NO:75) FIG. 9A). The construct had a GM-CSF derived signal peptide (encoding amino acid sequence of SEQ ID NO:65). The MERTK receptor tyrosine kinase transduces a signal for engulfment, and the C-terminal domain of the second FA58C repeat (C2) of MFP-E8 (referred to herein as FA58C2) has been shown to be responsible for phosphatidylserine binding (Hanayama et al., 2002, Nature, 417:182-7; Nishi et al., supra). The FA58C2-MERTK CER nucleotide sequence was then inserted into the pMSCV (murine stem cell virus) retroviral vector. Early passage murine Ba/F3 B-cells were transduced with pMSCV FA58C2-MERTK CER retrovirus expressing yellow fluorescent protein (GFP). Positive Ba/F3 transductants were sorted by GFP expression using flow cytometry (FACs), expanded in culture, and used for in vitro studies.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0359] Primary thymocytes were incubated with 10 .mu.M dexamethasone for 24 hours to induce cell death. Thymocytes were then labeled with 1 .mu.M of pHrodo Red dye in PBS for 15 minutes at room temperature, washed 2.times. with RPMI media containing 10% FBS, and used as target cells for phagocytosis assays. 50 .mu.l of pHrodo Red-labeled thymocytes (10.sup.6/mL) were incubated with 50 .mu.l of FA58C2-MERTK sorted Ba/F3 B-cells (10.sup.5/mL) (target cell to effector cell ratio of 10:1). Labeling target cells with pHrodo Red permits visualization of cells that are engulfed and transported into lysosomes due to their increased light emission in the acidic lysosomal environment (Miksa et al., supra). Co-culture experiments were carried out and Ba/F3 GFP+ cells were serially quantified for phagocytosis by fluorescence microscopy and FACs at 2 hr, 24 hr, 48 hr, and 72 hr. Ba/F3 cells transduced with pMSCV vector expressing Tim4 and GFP (non-engulfment receptor) were used as a negative control.

[0360] FA58C2-MERTK CER-mediated engulfment of apoptotic thymocytes was first examined (FIGS. 9B-9F). Expression of FA58C2-MERTK CER in murine Ba/F3 B-cells strongly enhanced phagocytic uptake of phosphatidylserine positive (PtdSer.sup.+) thymocytes (FIGS. 9B-9F). Observation by fluorescent microscopy and FACs show that the amount of phagocytosis correlates with incubation time with target cells, as well as the quantity of FA58C2-MERTK CER expression (FIGS. 9B-9C). Two hours following co-incubation, 11% of FA58C2-MERTK CER transduced Ba/F3 cells had engulfed, compared to 0% in control groups (FIG. 9B). The number of phagocytic Ba/F3 cells expressing FA58C2-MERTK CER increased to 48% at 24 hours incubation time (FIGS. 9B-9F). Furthermore, Ba/F3 cells that expressed the highest amount of FA58C2-MERTK CERs exhibited the greatest amount of phagocytosis (FIG. 9C), indicating a concentration dependent effect of the FA58C2-MERTK CER.

[0361] EFFECT OF SMALL GTPASE ON FA58C2-MERTK ENGULFMENT The effect of addition of small GTPase Rac1 and/or Rab5a on engulfment by CER-expressing Ba/F3 cells was tested. The Rho and Rab family GTPases regulate the engulfment of apoptotic cells by macrophages and immature dendritic cells. To form the phagocytic cup to engulf cells, integrin receptors expressed by macrophages activate Rac1 of the Rho family of GTPase to induce actin polymerization (Albert et al., 2000, Nat. Cell Biol. 2:899-905). Rab5, a member of the Rab family of GTPases, regulates the fusion of phagosomes with endosomes and may play a role in lysosome biogenesis (Duclos et al., 2000, J. Cell Sci. 113:3531-41). The cDNA sequence encoding Rac1 (SEQ ID NO: 60), Rab5 (SEQ ID NO: 61), or both (SEQ ID NO: 62) was co-expressed with FA58C2-MERTK using a bi-cistronic or tri-cistronic retroviral expression cassette (pMSCV FA58C2-MERTK-P2A-Rac1, pMSCV FA58C2-MERTK-P2A-Rab5a, or pMSCV FA58C2-MERTK-P2A-Rac1-T2A-Rab5a (FIG. 10A). As evident in FIGS. 10B-10E, the addition of Rac1 increased FA58C2-MERTK CER-mediated engulfment of target apoptotic thymocytes (56% vs. 48% as shown in FIG. 10E vs. FIG. 9F). Furthermore, transfer of ingested thymocytes into phagolysosomes was observed. Observation by fluorescence microscopy show several pHrodo Red-positive cells present inside most of FA58C2-MERTK CER/Rac1-expressing Ba/F3 B-cells (FIG. 10C).

Example 6

Construction of FA58C2-Syk CER "CER04"

[0362] The phosphatidylserine binding motif FA58C2 from the macrophage opsonin MFGE8 fused to a GM-CSF derived signal peptide was fused to a modified IgG4 extracellular spacer domain, the transmembrane domain of costimulatory molecule CD28, and the Syk kinase domain to create the chimeric engulfment receptor "CER04" (FA58C2-Syk CER) (polynucleotide sequence of SEQ ID NO:63, amino acid sequence of SEQ ID NO:70, FIG. 11A). Clustered Syk tyrosine kinase domains trigger phagocytosis in COS cells (Greenberg et al., 1996, Proc. Natl. Acad. Sci. USA 93:1103-7). The FA58C2-Syk CER nucleotide sequence was then inserted into the pMSCV (murine stem cell virus) retroviral vector. Early passage murine Ba/F3 B-cells were transduced with pMSCV FA58C2-Syk retrovirus expressing the GFP fluorescent protein. Positive Ba/F3 transductants were sorted by GFP expression using flow cytometry (FACs), expanded in culture, and used for in vitro studies.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0363] Primary thymocytes were induced into apoptosis and labeled with pHrodo Red dye as described in Example 4. Co-culture experiments were carried out and Ba/F3 GFP+ cells were serially quantified for phagocytosis by fluorescence microscopy and FACs as described in Example 4. Ba/F3 cells transduced with pMSCV vector expressing Tim4 and GFP (non-engulfment receptor) were used as a negative control.

[0364] FA58C2-Syk CER-mediated engulfment of apoptotic thymocytes was examined (FIGS. 11A-11E). Expression of FA58C2-Syk CER in the murine Ba/F3 B-cell line strongly enhanced phagocytic uptake of phosphatidylserine positive (PtdSer) thymocytes (FIGS. 11B-11E). Observation by fluorescent microscopy and FACs show that the amount of phagocytosis correlates with time of target cell incubation, as well as the quantity of FA58C2-Syk CER expression. Two hours following co-incubation, 9.5% of FA58C2-Syk CER-transduced Ba/F3 cells had engulfed target apoptotic thymocytes, compared to 0% in control groups (FIG. 11B). The number of phagocytic Ba/F3 cells expressing FA58C2-Syk CER increased to 48% at 24 hours incubation (FIGS. 11B, 11C, and 11E). Furthermore, Ba/F3 cells that expressed the highest amount of FA58C2-Syk CERs exhibited the greatest amount of phagocytosis (FIG. 11C), indicating a concentration dependent effect of the FA58C2-Syk CER.

Effect of Small GtPase Rab5 on FA58C2-Syk Engulfment

[0365] The effect of the addition of small GTPase Rac1 and/or Rab5a on engulfment by Ba/F3 cells was examined. The cDNA sequence encoding Rac1 (SEQ ID NO: 60) and/or Rab5 (SEQ ID NO: 61), or both (SEQ ID NO:62) was co-expressed with FA58C2-Syk CER using a bi-cistronic or tri-cistronic retroviral expression cassette (pMSCV FA58C2-Syk-P2A-Rac1, pMSCV FA58C2-Syk-P2A-Rab5a, and pMSCV FA58C2-Syk-P2A-Rac1-T2A-Rab5a constructs) (FIGS. 11A, 12A). As evident in FIGS. 11B and 11C, the addition of Rac1 increased FA58C2-Syk CER-mediated engulfment or target apoptotic thymocytes. Furthermore, the addition of Rab5 also increased phagocytosis (FIGS. 12B-12D).

Example 7

Construction of CD19-MERTK CER "CER40"

[0366] An anti-CD19 single chain fragment variable (scFv) (encoding amino acid sequence of SEQ ID NO:66) derived from the FMC63 mouse IgG2a mouse monoclonal antibody and fused to a GM-CSF derived signal peptide (encoding amino acid sequence of SEQ ID NO:65) was fused to a modified IgG4 extracellular spacer domain (encoding amino acid sequence of SEQ ID NO:67), transmembrane domain of costimulatory molecule CD28 (encoding amino acid sequence of SEQ ID NO:68), and the intracellular kinase domain of MERTK (amino acid sequence of SEQ ID NO:43) to create the chimeric engulfment receptor "CER40" (CD19-MERTK CER) (having amino acid sequence of SEQ ID NO:64) (FIG. 13A) (Kochenderfer et al., 2009, J. Immunother. 32:689-702). To enhance engulfment, a bi-cistronic retroviral expression construct comprising CD19-MERTK CER and Rac1 was constructed (FIG. 13B). The CD19-MERTK CER nucleotide sequence was then inserted into the pMSCV (murine stem cell virus) retroviral vector. Early passage murine Ba/F3 B-cells were transduced with pMSCV CD19-MERTK CER retrovirus expressing green fluorescent protein (GFP). Positive Ba/F3 transductants were sorted by GFP expression using flow cytometry (FACs), expanded in culture, and used for in vitro studies.

Phagocytic Activity Against Human Lymphoma Cell Line

[0367] Raji human Burkitt B-cell lymphoma cells, which are CD19.sup.+, were labeled with 1 .mu.M of pHrodo Red dye and used as target cells for phagocytosis assays as described in Example 4. Co-culture experiments were carried out and Ba/F3 GFP+ cells were serially quantified for phagocytosis by fluorescence microscopy and FACs as described in Example 4. Ba/F3 cells transduced with pMSCV vector expressing Tim4 and GFP (non-engulfment receptor) and non-transduced Ba/F3 cells were used as negative controls.

[0368] CD19-MERTK CER-mediated engulfment of Raji Burkitt B-cell lymphoma cells was first examined (FIGS. 13C-13F). Expression of CD19-MERTK CER in murine Ba/F3 B-cell line strongly enhanced phagocytic uptake of Raji lymphoma cells (FIGS. 13C-13G). Observation by fluorescent microscopy and FACs show that the amount of phagocytosis correlates with time of target cell incubation, as well as the quantity of CD19-MERTK CER expression. 24 hours following co-incubation, 17% of CD19-MERTK-P2A-Rac1 CER transduced Ba/F3 cells had engulfed Raji Burkitt B-cell lymphoma cells, compared to 0% in control groups (FIG. 13C, 13G). Ba/F3 cells that expressed the highest amount of CD19-MERTK CERs exhibited the greatest amount of phagocytosis (FIG. 13D), indicating a concentration dependent effect of the CD19-MERTK CER.

[0369] The ability of the CD19-MERTK CER to facilitate transfer of ingested Raji cells into phagolysosomes was examined. Fluorescence microscopy showed that pHrodo Red-positive whole Raji cells were present inside CD19-MERTK CER+Rac1-expressing Ba/F3 cells (FIG. 13E). FIG. 13H shows engulfment of Raji cells by CD19-MERTK CER expressing Ba/F3 cells (white arrows indicate phagocytosis). These results demonstrate the capacity for CD19-MerTk CER-expressing to eliminate targets in a CD19-specific manner.

Example 8

Construction of Tim4-MERTK CER "CER01"

[0370] A Tim-4-MERTK chimeric engulfment receptor nucleotide sequence encoding CER01 having an amino acid sequence of SEQ ID NO:71, as described in Example 4, was inserted into a pLenti lentiviral vector. Murine Ba/F3 B-cells were cultured in RMPI 1640 media supplemented with 10% fetal bovine serum, 1% penicillin-streptomycin, and 10 ng/mL murine IL-3 (Peprotech Catalog #213-13) in a 12 well plate at a density of 0.5 million cells/ml. To transduce Ba/F3 cells, 100 .mu.l of pLenti lentivirus vector expressing Tim4-MERTK (CER01) and truncated EGFR (also referred to as tEGFR or EGFRt) as a transduction marker (see, FIG. 16) and 5 .mu.l TRANSDUX.TM. transduction reagent were diluted in 0.5 ml Complete Cell Growth Media and added to the Ba/F3 cells. The Ba/F3 cells were then centrifuged at 270.times.g rpm for 1 hour in a 32.degree. C. pre-warmed centrifuge. The Ba/F3 cells were incubated for 24 hours at 37.degree. C. Ba/F3 cells were expanded for another 48 hours in Complete Cell Growth Media. Positive Ba/F3 cell transductants were sorted using fluorescence activated cell sorting (FACs) (Sony Sorter SH800) by either staining with a labeled Tim4 specific antibody (Kat5-18, Abcam Catalog #176486) or a labeled EGFR-specific antibody (Cetixumab) (see, FIGS. 17A-B). Post sorting, purified, transduced Ba/F3 cells comprising the Tim4-MERTK-T2A-truncated EGFR containing lentivirus (see, FIG. 17C) were rested for 48 hours prior to being utilized for phagocytic assays. Percentage of cells with positive staining is indicated in each histogram.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0371] One day prior to phagocytic assay, primary thymocytes were isolated from a C3H mouse (Charles River Laboratories International, Inc.). Thymocytes were cultured in complete RPMI 1640 growth media supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a 6-well plate. To induce apoptosis and phosphatidylserine expression on the cell surface, thymocytes were treated with 1 .mu.M dexamethansone for 24 hours. Untreated thymocytes were used as a negative control. Thymocytes were collected from the 6-well plates, washed once with sterile 1.times.PBS, and then stained with 1 ng/.mu.l pH sensitive pHrodo.TM. Red dye (ThermoFisher Scientific, Catalog # P36600) in PBS at room temperature for 15 minutes. The cells were then supplemented with growth media and washed one more time to remove any excess pHrodo Red. pHrodo Red stained thymocytes were plated on a flat bottom 96 well plate at 250,000 cells/well in RMPI 1640 complete media.

[0372] Ba/F3 CER01.sup.+ tEGFR.sup.+ cells made as described above were washed once with 1.times.PBS and stained with 1 .mu.M CELLTRACE.TM. Violet dye (ThermoFisher Scientific, Catalog # C34557) in PBS for 10 minutes at 37.degree. C. Stained, transduced Ba/F3 cells were supplemented with growth media, washed once with 1.times.PBS to remove excess CELLTRACE.TM. Violet, and plated on the same flat bottom 96 well plate at approximately 25,000 cells/well in RPMI 1640 complete media.

[0373] Target thymocytes were co-cultured with stained, Ba/F3 CER01.sup.+ tEGFR.sup.+ cells at a ratio of 10:1 (target cell:effector cell) for 3 hours or overnight (.about.14 hours) at 37.degree. C. After incubation, the plate was centrifuged and the media replaced with PBS supplemented with 2% fetal bovine serum, pH 9. The 96 well plate was then viewed using KEYENCE BZ-X710 fluorescence microscope, 20.times. objective. A duplicate 96-well co-culture plate was also set up in parallel for analysis by flow cytometry. 7-aminoactinomycin D (7-AAD) dye was used as a cell viability dye along with pHrodo Red stained target thymocytes and CELLTRACE Violet stained effector cells. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscopy showed that CER01.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) (see, FIG. 18B) as compared to truncated EGFR transduced Ba/F3 control cells (see, FIG. 18A). High magnification of an engulfment event is shown in the bottom right of FIG. 18B.

[0374] The amount of Ba/F3 effector cells as measured by FACS is depicted in FIG. 19A. Phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as measured by FACS (see, FIG. 19B).

[0375] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIGS. 20A-B).

Phagocytic Activity Against Murine Cell Lines

[0376] One day prior to the phagocytosis assay, CT26 murine colon carcinoma cells were cultured in complete RPMI 1640 growth media supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a 6-well plate and treated with 1 mM staurosporine (STS) for 12 hours to induce apoptosis. Untreated CT26 cells were used as a negative control.

[0377] On the day of the phagocytosis assay, CT26 cells were collected, washed twice with 1.times.PBS to remove excess staurosporine and then stained with 1 ng/l pHrodo Red in PBS at room temperature for 15 minutes. The CT26 cells were supplemented with growth media, washed once to remove excess pHrodo Red, and plated onto a flat bottom, 96 well plate at 250,000 cells/well in RPMI 1640 complete media.

[0378] Ba/F3 CER01.sup.+ EGFR.sup.+ cells made as described above were washed once with 1.times.PBS and stained with 1 .mu.M CELLTRACE.TM. Violet dye (ThermoFisher Scientific, Catalog # C34557) in PBS for 10 minutes at 37.degree. C. Stained, transduced Ba/F3 cells were supplemented with growth media, washed once with 1.times.PBS to remove excess CELLTRACE.TM. Violet, and plated on the same flat bottom 96 well plate at approximately 50,000 cells/well in RPMI 1640 complete media.

[0379] Target CT26 cells were co-cultured with stained, CER01.sup.+ tEGFR.sup.+ cells at a ratio of 5:1 (target cell:effector cell) for 3 hours at 37.degree. C. After incubation, the plate was centrifuged and the media replaced with PBS supplemented with 2% fetal bovine serum, pH 9. The 96 well plate was then viewed using KEYENCE BZ-X710 fluorescence microscope, 20.times. objective. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as negative control. Fluorescent micrograph showing in vitro phagocytosis is shown in FIG. 21 (white arrows show phagocytosis events). CT26 cells labeled with pHrodo Red fluoresced inside the low pH compartments of lysosomes when engulfed (outlined in pink).

[0380] A hybrid capture algorithm that detects fluorescence of pHrodo Red within CELLTRACE Violet staining area was applied to fluorescent images to quantify the area of engulfed target cells/area of CER.sup.+ B cells. FIG. 22 shows histogram plots of hybrid cell counts extracting CT26 target cell area within Ba/F3 cells transduced with CER01.sup.+ EGFR.sup.+ (FIG. 22A) or EGFR.sup.+ control (FIG. 22B). FIG. 23 shows a scatterplot of hybrid cell counts extracting CT26 target cell area within Ba/F3 cells transduced with CER01.sup.+ EGFR.sup.+ or EGFR.sup.+ control. The area ratio represents the co-localization area of CT26 cells within Ba/F3 cells. Frequency of phagocytosis of Ba/F3 cells transduced with CER01.sup.+ EGFR.sup.+ or EGFR.sup.+ control is shown in FIG. 24A. A phagocytic index for CER01+ Ba/F3 cells as compared to EGFRt transduced Ba/F3 control cells is shown in FIG. 24B.

[0381] Ba/F3 CER01.sup.+ EGFR.sup.+ cells were transduced, purified, expanded, and labeled with CELLTRACE.TM. Violet dye as described above. A20 murine B cell lymphoma cells were treated with staurosporine, stained with pHrodo Red, co-cultured with stained CER01.sup.+ tEGFR.sup.+ cells at a ratio of 5:1 (target cell:effector cell) as described above for the phagocytosis assay with CT26 cells. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as negative control. Phagocytic events were quantified by fluorescent microscopy (KEYENCE BZ-X710 fluorescence microscope, 20.times. objective) using the hybrid capture algorithm described above for the assay with CT26 cells.

[0382] A fluorescent microscope image showing in vitro phagocytosis of target A20 cells is shown in FIG. 25 (white arrows showing phagocytosis events). FIG. 26 shows histogram plots of hybrid cell counts extracting A20 target cell area within Ba/F3 cells transduced with CER01.sup.+ EGFR.sup.+ (FIG. 26A) or EGFR.sup.+ control (FIG. 26B). FIG. 27 shows a scatterplot of hybrid cell counts extracting A20 target cell area within Ba/F3 cells transduced with CER01.sup.+ EGFR.sup.+ or EGFR.sup.+ control. The area ratio represents the co-localization area of A20 cells within Ba/F3 cells. A phagocytic index for CER01+Ba/F3 cells as compared to EGFRt transduced Ba/F3 control cells is shown in FIG. 28.

[0383] Ba/F3 CER01.sup.+ EGFR.sup.+ cells were also co-cultured with staurosporine treated WR19L murine T cell lymphoma cells as described above in the assay for CT26 cells using a target cell to effector cell ratio of 5:1 and co-incubation time of 3 hours. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as negative control. Phagocytosis of WR19L cells by CER01.sup.+ Ba/F3 cells was quantified by fluorescence microscopy as described above. A fluorescent microscope image showing in vitro phagocytosis is shown in FIG. 29 (white arrows show phagocytosis events). FIG. 30 shows frequency of WR19L cell phagocytosis by Ba/F3 cells transduced with CER01.sup.+ EGFR.sup.+ (+ or - staurosporine (STS)) or EGFR.sup.+ control.

Phagocytic Activity of Human CER01+ B Cells Against Human Cell Line

[0384] Human primary B cells were transduced with pLenti Tim4-MERTK (CER01) lentivirus expressing truncated EGFR as a transduction marker as described above for Ba/F3 cells, except transduced human B cells were sorted by FACS with a labeled anti-EGFR antibody (Cetuximab) and then stained with a Kat5-18 antibody (Tim4 specific) (Abcam Catalog #176486) (see, FIG. 31A where the % in the right FACS plot represents the % of cells expressing Tim4 binding domain (CER01)). Purified CER01.sup.+ B cells were expanded, and imaged at 24 hours, 48 hours, and 72 hours shown in FIG. 31B.

[0385] One day prior to setting up the phagocytosis assay, Jurkat human B lymphocytes were cultured in complete RPMI 1640 growth media supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a 6 well plate and treated with 1 mM staurosporine for three hours to induce apoptosis. Jurkat cells were washed twice in 1.times.PBS to remove excess staurosporine and then stained with pHrodo Red (1 ng/.mu.l in PBS) for 15 minutes at room temperature. The Jurkat cells were supplemented with growth media, washed once to remove excess pHrodo Red, and plated on flat bottom 96 well plates at approximately 250,000 cells/well in RPMI 1640 complete media.

[0386] Transduced human primary B cells were washed once with 1.times.PBS and stained with 1 .mu.M CELLTRACE Violet in PBS for 10 minutes at 37.degree. C. The human primary B cells were supplemented with growth media, washed once with 1.times.PBS to remove excess CELLTRACE Violet, and plated onto 96 well plate at approximately 50,000 cells/well in RPMI 1640 complete media. Human primary B cells and Jurkat cells were co-cultured at a target cell to effector cell ratio of 5:1 at 37.degree. C. for 3 hours. After incubation, the co-culture plate was then centrifuged, and the media replaced with PBS supplemented with 2% fetal bovine serum, pH 9. Phagocytic events were quantified by fluorescent microscopy (KEYENCE BZ-X710 fluorescence microscope, 20.times. objective). Fluorescent microscope image showing in vitro phagocytosis is shown in FIG. 32A for CER01.sup.+ B cells and in FIG. 32B for EGFR+ control (white arrows show phagocytosis events).

[0387] A duplicate 96-well co-culture plate was also set up in parallel for analysis by flow cytometry using a 10:1 target cell to effector cell ratio (approximately 300,000 cells/well pHrodo Red labeled, staurosporine treated Jurkat cells co-cultured with approximately 30,000 cells/well CER01.sup.+ transduced human primary B cells). The co-culture plate was centrifuged at 1200 rpm for 5 minutes, media replaced with FACS buffer (PBS+2% fetal bovine serum) containing a 1:50 dilution of allophycocyanin (APC) labeled CD19 antibody to stain human primary B cells. The human primary B cells were incubated with APC labeled CD19 antibody for 30 minutes at 4.degree. C., washed once, and the cell culture plates were supplemented with FACS buffer containing DAPI (4',6-diamidino-2-phenylindole), which was used as a marker for cell viability. During FACS analysis, gating was performed on viable CD19-APC positive cells (see, FIG. 33 left FACS plot) and evaluated for frequency of CD19 positive-pHrodo Red positive events (double positive events), which were defined as phagocytosis events (see, FIG. 33 right FACS plot). FIG. 34 shows frequency of Jurkat cell phagocytosis by B cells transduced with CER01+ EGFR+ or EGFR+ control.

Phagocytic Activity of Human CER01 B Cells Against Chemotherapy-Treated Human Cell Line

[0388] Human primary B cells were transduced with pLenti Tim4-MERTK (CER01) lentivirus expressing truncated EGFR as a transduction marker as described above. One day prior to setting up the phagocytosis assay, Jurkat human B lymphocyte cells were cultured in complete RPMI 1640 growth media supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a 6 well plate and treated with oxaliplatin (5 .mu.M) and fluorouracil (5-FU) (10 .mu.M). The following day, target Jurkat cells were collected, washed twice with 1.times.PBX, and stained with pHrodo Red (1 ng/mL in PBS) for 15 minutes at room temperature. The Jurkat cells were supplemented with growth media, washed once to remove excess pHrodo Red, and plated on flat bottom 96 well plates at approximately 200,000 cells/well in RPMI 1640 complete media. Transduced human primary B cells were washed once with 1.times.PBS and then stained with CELLTRACE Violet (1 mM in PBS) for 10 minutes at 37.degree. C. The human primary B cells were supplemented with growth media, washed once with 1.times.PBS to remove excess CELLTRACE Violet, and plated onto a 96 well plate at approximately 50,000 cells in RPMI complete media. Human primary B cells and Jurkat cells were co-cultured at a target cell to effector cell ratio of 4:1 at 37.degree. C. for 3 hours. The plate was then imaged using a 20.times. objective, Keyence BZ-X710 microscope. FIG. 35 shows fluorescent microscope images showing engulfment of chemotherapy treated Jurkat cells by CER01+ human primary B cells (right image shows enlargement of a phagocytosis event; white arrows indicate phagocytosis).

Example 9

Construction of Tim4-Tyro3 CER "CER08"

[0389] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) (together having a polynucleotide sequence of SEQ ID NO:57), were fused to the intracellular signaling domain of the Tyro3 (SEQ ID NO:45) to create a chimeric engulfment receptor "CER08" (Tim4-Tyro3 CER having an amino acid sequence of SEQ ID NO:83). The Tyro3 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-Tyro3 (CER08) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 36). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-Tyro3 (CER08) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0390] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER08.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER08.sup.+tEGFR.sup.+ cells were quantified for phagocytosis by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0391] The quantity of viable, CER08+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 37A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 37B).

[0392] Fluorescent microscopy showed that CER08.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes as compared to tEGFR transduced Ba/F3 control cells (white arrows indicate engulfment events) (see, FIG. 38). High magnification of an engulfment event is shown in the right of FIG. 38.

[0393] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIGS. 39A-B).

Example 10

Construction of Tim4-DAP12 CER "CER09"

[0394] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) (together having a polynucleotide sequence of SEQ ID NO: 57), were fused to the intracellular signaling domain of DAP12 (SEQ ID NO:82) to create a chimeric engulfment receptor "CER09" (Tim4-DAP12 CER having an amino acid sequence of SEQ ID NO:84). The DAP12 transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-DAP12 (CER09) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 40). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-DAP12 (CER09) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0395] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER09.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER09.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER09.sup.+ EGFR.sup.+ cells were quantified for phagocytosis by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0396] The quantity of viable, CER09+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 41A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 41B).

[0397] Fluorescent microscopy showed that CER09+Ba/F3 cells engulf dexamethasone-treated thymocytes as compared to tEGFR transduced Ba/F3 control cells (white arrows indicate engulfment events) (see, FIGS. 42A-B). High magnification of an engulfment event is shown in the right of FIG. 42B.

[0398] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIGS. 43A-B).

Phagocytic Activity Against Murine Cell Lines

[0399] Ba/F3 CER09.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. CT26 murine colon carcinoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with Ba/F3 CER09.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of CT26 cells by CER09+Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope images showing in vitro phagocytosis by CER09+Ba/F3 cells and EGFRt+ control cells are shown in FIGS. 44A-B (white arrows show phagocytosis events). CT26 cells labeled with pHrodo Red fluoresce inside the low pH compartments of lysosomes when engulfed (outlined in pink).

[0400] A hybrid capture algorithm that detects fluorescence of pHrodo Red within CELLTRACE Violet staining area was applied to fluorescent images to quantify the area of engulfed target cells/area of CER.sup.+ B cells. FIG. 45 shows a scatterplot of hybrid cell counts extracting CT26 target cell area within Ba/F3 cells transduced with CER09.sup.+ tEGFR.sup.+ or tEGFR.sup.+ control. The area ratio represents the co-localization area of CT26 cells within Ba/F3 cells. A phagocytic index for CER09+Ba/F3 cells as compared to EGFRt transduced Ba/F3 control cells is shown in FIG. 46.

[0401] WR19L murine lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER09.sup.+ EGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of WR19L cells by CER09+Ba/F3 cells was quantified by fluorescence microscopy as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope imaging showed in vitro phagocytosis of WR19L cells by CER09+Ba/F3 cells is shown in FIG. 47 (white arrows show phagocytosis events).

[0402] A20 murine lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER09.sup.+ EGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of A20 cells by CER09+Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of A20 cells by CER09+Ba/F3 cells is shown in FIG. 48 (white arrows show phagocytosis events).

Phagocytic Activity of Human CER09+ B Cells Against Human Cell Line

[0403] Human primary B cells were transduced with pLenti Tim4-DAP12 (CER09) lentivirus expressing truncated EGFR as a transduction marker as described in Example 8. Transduced human B cells were sorted by FACS with a labeled anti-EGFR antibody (Cetuximab) and then stained with a Kat5-18 antibody (Tim4 specific) (Abcam Catalog #176486) (see, FIG. 49A where the % in the right FACS plot represents the % of cells expressing Tim4 binding domain (CER09)). Purified CER09.sup.+ B cells were expanded, and imaged at 24 hours, 48 hours, and 72 hours shown in FIG. 49B.

[0404] Jurkat human T lymphocytes were treated with staurosporine, labeled with pHrodo Red, and co-cultured with CER09+ primary B cells in a phagocytosis assay as described in Example 8 using a target cell to effector cell ratio of 5:1 and co-incubation time of 3 hours. Phagocytosis of Jurkat cells by CER09.sup.+ human B cells was quantified by fluorescence microscopy and FACs as described in Example 8. The frequency of viable CD19 positive human primary B cells and frequency of CD19 positive-pHrodo Red positive events (double positive events) are shown in FIG. 50 (left and right plots, respectively). FIG. 51 shows frequency of phagocytosis of B cells transduced with CER09+tEGFR+ or EGFR+ control.

[0405] A fluorescent microscope image showing in vitro phagocytosis of Jurkat cells by CER09.sup.+ human primary B cells is shown in FIG. 52 (left photo), and phagocytosis of Jurkat cells by tEGFR+ human primary B cells control is shown in FIG. 52 (right photo) (white arrows show phagocytosis events).

Example 11

Construction of Tim4-DAP12-DAP12 CER "CER10"

[0406] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) were fused to the DAP12 transmembrane (SEQ ID NO:81) and intracellular signaling (SEQ ID NO:82) to create a chimeric engulfment receptor "CER10" (Tim4-DAP12-DAP12 CER having an amino acid sequence of SEQ ID NO:86). The DAP12 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-DAP12-DAP12 (CER10) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by P2A sequence (SEQ ID NO: 104) (see, FIG. 53). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-DAP12-DAP12 (CER10) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0407] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER10.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER10.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER10.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0408] The quantity of viable, CER10+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 54A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 54B).

[0409] Fluorescent microscopy showed that CER10.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIGS. 55A-B). High magnification of an engulfment event is shown in the bottom right of FIG. 55B.

[0410] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIGS. 56A-B).

Example 12

Construction of TIM4-Axl CER "CER11"

[0411] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to the Axl intracellular signaling (SEQ ID NO:44) to create a chimeric engulfment receptor "CER11" (Tim4-Axl CER having an amino acid sequence of SEQ ID NO:87). The Axl signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-Axl (CER11) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 49). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-Axl (CER11) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0412] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER11.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER11.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER11.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0413] The quantity of viable, CER11+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 58A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 58B).

[0414] Fluorescent microscopy showed that CER11.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIGS. 59A-B). High magnification of an engulfment event is shown in the right of FIG. 59B.

[0415] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIGS. 60A-B).

Phagocytic Activity Against Murine Cell Lines

[0416] Ba/F3 CER11.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. CT26 murine colon carcinoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with Ba/F3 CER11.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of CT26 cells by CER11 Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope images showing in vitro phagocytosis by CER11+Ba/F3 cells and EGFRt.sup.+ control Ba/F3 cells are shown in FIGS. 61A-B (white arrows show phagocytosis events). CT26 cells labeled with pHrodo Red fluoresce inside the low pH compartments of lysosomes when engulfed (outlined in pink).

[0417] A hybrid capture algorithm that detects fluorescence of pHrodo Red within CELLTRACE Violet staining area was applied to fluorescent images to quantify the area of engulfed target cells/area of CER.sup.+ B cells. FIG. 62 shows a scatterplot of hybrid cell counts extracting CT26 target cell area within Ba/F3 cells transduced with CER11.sup.+ tEGFR.sup.+ or tEGFR.sup.+ control. The area ratio represents the co-localization area of CT26 cells within Ba/F3 cells.

[0418] WR19L murine lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER11.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of WR19L cells by CER11.sup.+ Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of WR19L cells by CER11+Ba/F3 cells is shown in FIG. 63 (white arrow shows phagocytosis events). The quantity of viable, CER11+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 64A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 64B).

[0419] A20 murine cell lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER11.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of A20 cells by CER11 Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of A20 cells by CER11+Ba/F3 cells is shown in FIG. 65A (white arrow show phagocytosis events) as compared to EGFRt transduced Ba/F3 control (FIG. 65B). Phagocytic index was calculated or CER11+Ba/F3 cells as compared to EGFRt+ control cells and is shown in FIG. 66.

Phagocytic Activity of Human CER11.sup.+ B Cells Against Chemotherapy-Treated Human Cell Line

[0420] Human primary B cells were transduced with pLenti Tim4-Axl (CER11) lentivirus expressing truncated EGFR as a transduction marker as described in Example 8. One day prior to setting up the phagocytosis assay, Jurkat human B lymphocyte cells were cultured in complete RPMI 1640 growth media supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a 6 well plate and treated with oxaliplatin (5 .mu.M) and fluorouracil (5-FU) (10 .mu.M). The following day, target Jurkat cells were collected, washed twice with 1.times.PBX, and stained with pHrodo Red (1 ng/mL in PBS) for 15 minutes at room temperature. The Jurkat cells were supplemented with growth media, washed once to remove excess pHrodo Red, and plated on flat bottom 96 well plates at approximately 200,000 cells/well in RPMI 1640 complete media. Transduced human primary B cells were washed once with 1.times.PBS and then stained with CELLTRACE Violet (1 mM in PBS) for 10 minutes at 37.degree. C. The human primary B cells were supplemented with growth media, washed once with 1.times.PBS to remove excess CELLTRACE Violet, and plated onto a 96 well plate at approximately 50,000 cells in RPMI complete media. Human primary B cells and Jurkat cells were co-cultured at a target cell to effector cell ratio of 4:1 at 37.degree. C. for 3 hours. The plate was then imaged using a 20.times. objective, Keyence BZ-X710 microscope. FIG. 67 shows fluorescent microscope images showing engulfment of chemotherapy treated Jurkat cells by CER11+ human primary B cells (right image shows an enlargement of a phagocytosis event; white arrows indicate phagocytosis).

[0421] Human primary B cells were transduced with pLenti Tim4-Axl (CER11) lentivirus expressing truncated EGFR as a transduction marker as described in Example 8. One day prior to setting up the phagocytosis assay, Colo320 HSR colon cancer cells were incubated with phosphatidylserine inducing chemotherapy Gemcitabine (10 .mu.M) in serum-free media for 24 hours. Floating and adherent target cells after the treatment were collected, centrifuged, incubated with pHrodo red (1 ng/.mu.L) for 15 minutes at room temperature in PBS, washed and then plated in a non-adherent 96 well plate. Human CER11+ expressing B cells and Colo320HSR cells were co-cultured at a target cell to effector cell ratio of 4:1 at 37.degree. C. for 3 hours. The plate was then imaged using a 20.times. objective, Keyence BZ-X710 microscope (see, FIG. 68; white arrows shows phagocytic events).

[0422] Human primary B cells were transduced with pLenti Tim4-Axl (CER11) lentivirus expressing truncated EGFR as a transduction marker as described in Example 8. One day prior to setting up the phagocytosis assay, A204 rhabdomyosarcoma cells were incubated in phosphatidylserine inducing chemotherapy Paclitaxel, and H1703 non-small cell lung cancer (NSCLC) adenocarcinoma cancer cells were incubated with phosphatidylserine inducing chemotherapy Paclitaxel (30 .mu.M)+Gemcitabine (10 .mu.M) in serum-free media for 24 hours. Floating and adherent target cells after the treatment were collected, centrifuged, incubated with pHrodo red (1 ng/.mu.L) for 15 minutes at room temperature in PBS, washed and then plated in a non-adherent 96 well plate. Human CER11+ expressing B cells and A204 or H1703 cells were co-cultured at a target cell to effector cell ratio of 4:1 at 37.degree. C. for 3 hours. The plate was then imaged using a 20.times. objective, Keyence BZ-X710 microscope (see, FIG. 69 for A204 cells and FIG. 70 for H1703 cells; arrows show phagocytic events).

Example 13

Construction of Tim4-Fc.epsilon.R1.gamma. CER "CER12"

[0423] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to the Fc.epsilon.R1.gamma. intracellular signaling (SEQ ID NO:88) to create a chimeric engulfment receptor "CER12" (Tim4-Fc.epsilon.R1.gamma. CER having an amino acid sequence of SEQ ID NO:90). The Fc.epsilon.R1.gamma. signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-Fc.epsilon.R1.gamma. (CER12) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 71). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-Fc.epsilon.R1.gamma. (CER12) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0424] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER12.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER12.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER12.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0425] The quantity of viable, CER12+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 72A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 72B).

[0426] Fluorescent microscopy showed that CER12+Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIGS. 73A-B). High magnification of an engulfment event is shown in the right of FIG. 73B.

[0427] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIGS. 74A-B).

Phagocytic Activity Against Murine Cell Lines

[0428] WR19L murine lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER12.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of WR19L cells by CER12.sup.+ Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of WR19L cells by CER12+Ba/F3 cells is shown in FIG. 75 (white arrow show phagocytosis events).

[0429] A20 murine B cell lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER12.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of A20 cells by CER12.sup.+ Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of A20 cells by CER12+Ba/F3 cells is shown in FIG. 76 (white arrow shows phagocytosis event). Phagocytic index was calculated for CER12+Ba/F3 cells as compared to EGFRt transduced Ba/F3 control cells and is shown in FIG. 77.

Example 14

Construction of Tim4-Fc.epsilon.R1.gamma.-Fc.epsilon.R1 CER "CER13"

[0430] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and were fused to the Fc.epsilon.R1.gamma. transmembrane domain (amino acid sequence of SEQ ID NO:89) and intracellular signaling (SEQ ID NO:88) to create a chimeric engulfment receptor "CER13" (Tim4-Fc.epsilon.R1.gamma.-Fc.epsilon.R1.gamma. CER having an amino acid sequence of SEQ ID NO:91). The Fc.epsilon.R1.gamma. signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-Fc.epsilon.R1.gamma.-Fc.epsilon.R1.gamma. (CER13) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 78). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-Fc.epsilon.R1.gamma.-Fc.epsilon.R1.gamma. (CER13) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0431] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER13.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER13.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER13.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0432] The quantity of viable, CER13+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 64A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 64B).

Phagocytic Activity of Human CER13.sup.+ B Cells Against Chemotherapy-Treated Human Cell Line

[0433] Human primary B cells were transduced with pLenti Tim4-Fc.epsilon.R1.gamma.-Fc.epsilon.R1.gamma. (CER13) lentivirus expressing truncated EGFR as a transduction marker as described in Example 11. One day prior to setting up the phagocytosis assay, Colo320 HSR colon cancer cells were incubated with phosphatidylserine inducing chemotherapy Gemcitabine (10 .mu.M) and Paclitaxel (30 .mu.M) in serum-free media for 24 hours. Floating and adherent target cells after the treatment were collected, centrifuged, incubated with pHrodo red (1 ng/.mu.L) for 15 minutes at room temperature in PBS, washed and then plated in a non-adherent 96 well plate. Human CER13+ expressing B cells and Colo320HSR cells were co-cultured at a target cell to effector cell ratio of 4:1 at 37.degree. C. for 3 hours. The plate was then imaged using a 20.times. objective, Keyence BZ-X710 microscope (FIG. 80, arrows show phagocytic events).

[0434] Human primary B cells were transduced with pLenti Tim4-Fc.epsilon.R1.gamma.-Fc.epsilon.R1.gamma. (CER13) lentivirus expressing truncated EGFR as a transduction marker as described in Example 11. One day prior to setting up the phagocytosis assay, A204 rhabdomyosarcoma cells were incubated with phosphatidylserine inducing Paclitaxel (30 .mu.M) chemotherapy and H1703 Non Small Cell Lung Cancer (NSCLC) adenocarcinoma cancer cells were incubated with phosphatidylserine inducing Paclitaxel (30 .mu.M)+Gemcitabine (10 .mu.M) chemotherapy in serum-free media for 24 hours. Floating and adherent target cells after the treatment were collected, centrifuged, incubated with pHrodo red (1 ng/.mu.L) for 15 minutes at room temperature in PBS, washed and then plated in a non-adherent 96 well plate. Human CER13+ expressing B cells and A204 or H1703 cells were co-cultured at a target cell to effector cell ratio of 4:1 at 37.degree. C. for 3 hours. The plate was then imaged using a 20.times. objective, Keyence BZ-X710 microscope (see, FIG. 81 for A204 cells and FIG. 82 for H1703 cells; arrows indicate phagocytic events).

Example 15

Construction of Tim4-MyD88t CER "CER15"

[0435] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to a truncated MyD88 (MyD88t) comprising a death domain but lacking the TIR domain (SEQ ID NO:78) to create a chimeric engulfment receptor "CER15" (Tim4-MyD88t CER having an amino acid sequence of SEQ ID NO:79). The truncated MyD88 transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MyD88t (CER15) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 83). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MyD88t (CER15) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0436] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER15.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER15.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER15.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0437] The quantity of viable, CER15+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 84A. The frequency of phagocytosis was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 84B).

[0438] Fluorescent microscopy showed that CER15.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIGS. 85A-B). High magnification of an engulfment event is shown in the right of FIG. 85B.

[0439] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIGS. 86A-B).

Phagocytic Activity Against Murine Cell Lines

[0440] Ba/F3 CER15.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. CT26 murine colon carcinoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with Ba/F3 CER15.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of CT26 cells by CER15.sup.+ Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of CT26 cells by CER15+Ba/F3 cells is shown in FIG. 87 (white arrows show phagocytosis events). CT26 cells labeled with pHrodo Red fluoresce inside the low pH compartments of lysosomes when engulfed (outlined in pink).

[0441] WR19L murine lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER15.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of WR19L cells by CER15.sup.+ Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of WR19L cells by CER15+Ba/F3 cells is shown in FIG. 88 (white arrow show phagocytosis events).

[0442] A20 murine lymphoma cells were treated with staurosporine, labeled with pHrodo Red and co-cultured with CELLTRACE Violet labeled Ba/F3 CER15.sup.+ tEGFR.sup.+ cells at a target cell to effector cell ratio of 5:1 for 3 hours as described in Example 8. Phagocytosis of A20 cells by CER15.sup.+ Ba/F3 cells was quantified by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control. Fluorescent microscope image showing in vitro phagocytosis of A20 cells by CER15+Ba/F3 cells is shown in FIG. 89 (white arrow show phagocytosis events).

Phagocytic Activity of Human CER15.sup.+ B Cells Against Human Cell Line

[0443] Human primary B cells were transduced with pLenti Tim4-MyD88t (CER15) lentivirus expressing truncated EGFR as a transduction marker as described in Example 8. Transduced human B cells were sorted by FACS with a labeled anti-EGFR antibody (Cetuximab) and then stained with a Kat5-18 antibody (Tim4 specific) (Abcam Catalog #176486) (see, FIG. 90A where the % in the right FACS plot represents the % of cells expressing Tim4 binding domain (CER15)). Purified CER15.sup.+ B cells were expanded, and imaged at 24 hours, 48 hours, and 72 hours shown in FIG. 90B.

[0444] Jurkat human T lymphocytes were treated with staurosporine, labeled with pHrodo Red, and co-cultured with CER15+ primary B cells in a phagocytosis assay as described in Example 8 using a target cell to effector cell ratio of 5:1 and co-incubation time of 3 hours. Phagocytosis of Jurkat cells by CER15.sup.+ human B cells was quantified by fluorescence microscopy and FACs as described in Example 8. The frequency of viable CD19 positive human primary B cells and frequency of CD19 positive-pHrodo Red positive events (double positive events) are shown in FIG. 91 (left and right plots, respectively). FIG. 92 shows frequency of phagocytosis of Jurkat cells by primary human B cells transduced with CER15+ tEGFR+ or EGFR+ control.

[0445] A fluorescent microscope image showing in vitro phagocytosis of Jurkat cells by CER15.sup.+ human primary B cells is shown in FIG. 93A, and phagocytosis of Jurkat cells by tEGFR+ human primary B cells control is shown in FIG. 93B (white arrows show phagocytosis events).

Example 16

Construction of Tim4-MyD88 CER "CER16"

[0446] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to MyD88 signaling domain comprising the death domain and TIR domain (SEQ ID NO:53) to create a chimeric engulfment receptor "CER16" (Tim4-MyD88 CER having an amino acid sequence of SEQ ID NO:80). The MyD88 transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MyD88 (CER16) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 94). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MyD88 (CER16) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity of Human CER16.sup.+ B Cells Against Chemotherapy-Treated Human Cell Line

[0447] Human primary B cells were transduced with pLenti Tim4-MyD88 (CER16) lentivirus expressing truncated EGFR as a transduction marker as described in Example 8. One day prior to setting up the phagocytosis assay, Jurkat human B lymphocyte cells were cultured in complete RPMI 1640 growth media supplemented with 10% fetal bovine serum and 1% penicillin-streptomycin in a 6 well plate and treated with oxaliplatin (5 .mu.M) and fluorouracil (5-FU) (10 .mu.M). The following day, target Jurkat cells were collected, washed twice with 1.times.PBX, and stained with pHrodo Red (1 ng/mL in PBS) for 15 minutes at room temperature. The Jurkat cells were supplemented with growth media, washed once to remove excess pHrodo Red, and plated on flat bottom 96 well plates at approximately 200,000 cells/well in RPMI 1640 complete media. Transduced human primary B cells were washed once with 1.times.PBS and then stained with CELLTRACE Violet (1 mM in PBS) for 10 minutes at 37.degree. C. The human primary B cells were supplemented with growth media, washed once with 1.times.PBS to remove excess CELLTRACE Violet, and plated onto a 96 well plate at approximately 50,000 cells in RPMI complete media. Human primary B cells and Jurkat cells were co-cultured at a target cell to effector cell ratio of 4:1 at 37.degree. C. for 3 hours. The plate was then imaged using a 20.times. objective, Keyence BZ-X710 microscope. FIG. 95 shows fluorescent microscope images showing engulfment of chemotherapy treated Jurkat cells by CER16+ human primary B cells (white arrows indicate phagocytosis).

Example 17

Construction of Tim4-NFAM1 CER "CER25"

[0448] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to NFAM1 signaling domain (SEQ ID NO:92) to create a chimeric engulfment receptor "CER25" (Tim4-NFAM1 CER having an amino acid sequence of SEQ ID NO:93). The NFAM1 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-NFAM1 (CER25) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 96). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-NFAM1 (CER25) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0449] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER25.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER25.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER25.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0450] Viable, CER25+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 97. The frequency of phagocytosis by CER25+Ba/F3 cells co-cultured with dexamethasone treated thymocytes was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 97B). Frequency of double positive staining cells for control Ba/F3 cells transduced with truncated EGFR and co-cultured with dexamethasone treated thymocytes is shown in FIG. 97A.

[0451] Fluorescent microscopy showed that CER25.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIG. 98 High magnification of an engulfment event is shown in the right of FIG. 98).

[0452] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIG. 99).

Example 18

Construction of Tim4-MyD88t-BAFFR CER "CER85"

[0453] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a truncated MyD88 (SEQ ID NO:78) and a secondary signaling domain comprising a BAFF-R signaling domain (SEQ ID NO:94) to create a chimeric engulfment receptor "CER85" (Tim4-MyD88t-BAFFR CER having an amino acid sequence of SEQ ID NO:95). The MyD88t or BAFF-R signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MyD88t-BAFF4 (CER85) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 100). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MyD88t-BAFFR (CER85) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0454] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER85.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER85.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER85.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0455] The quantity of viable, CER85+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 101. The frequency of phagocytosis by CER+85 Ba/F3 cells co-cultured with dexamethasone treated thymocytes was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 101A). Frequency of double positive staining cells for control Ba/F3 cells transduced with truncated EGFR and co-cultured with dexamethasone treated thymocytes is shown in FIG. 101B.

[0456] Fluorescent microscopy showed that CER85.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIG. 102, high magnification of an engulfment event is shown in the right of FIG. 102).

[0457] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIG. 103).

Example 19

Construction of Tim4-MyD88t-DAP12 CER "CER86"

[0458] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a truncated MyD88 (SEQ ID NO:78) and a secondary signaling domain comprising a DAP12 signaling domain (SEQ ID NO:82) to create a chimeric engulfment receptor "CER86" (Tim4-MyD88t-DAP12 CER having an amino acid sequence of SEQ ID NO:96). The MyD88t or DAP12 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MyD88t-DAP (CER86) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 104). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MyD88t-DAP12 (CER86) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 20

Construction of Tim4-BAFFR-MyD88 CER "CER87"

[0459] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a BAFF-R signaling domain (SEQ ID NO:94) and a secondary signaling domain comprising a truncated MyD88 signaling domain (SEQ ID NO:78) to create a chimeric engulfment receptor "CER8T" (Tim4-BAFFR-MyD88 CER having an amino acid sequence of SEQ ID NO: 130). The BAFF-R or truncated MyD88 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-BAFFR-MyD88 (CER87) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 105). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-BAFFR-MyD88 (CER87) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0460] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER87.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER87.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER87.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0461] The quantity of viable, CER87+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 106. The frequency of phagocytosis by CER87+Ba/Fe cells co-cultured with dexamethasone treated thymocytes was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 106B). Frequency of double positive staining cells for control Ba/F3 cells transduced with truncated EGFR and co-cultured with dexamethasone treated thymocytes is shown in FIG. 106A.

[0462] Fluorescent microscopy showed that CER87.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIG. 107). High magnification of an engulfment event is shown in the right of FIG. 107.

[0463] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIG. 108).

Example 21

Construction of Tim4-DAP12-MyD88 CER "CER88"

[0464] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a DAP12 signaling domain (SEQ ID NO:82) and a secondary signaling domain comprising a truncated MyD88 signaling domain (SEQ ID NO:78) to create a chimeric engulfment receptor "CER88" (Tim4-DAP12-tMyD88 CER having an amino acid sequence of SEQ ID NO:131). The DAP12 or truncated MyD88 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-DAP12-MyD88 (CER88) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 109). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-DAP12-MyD88 (CER88) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 22

Construction of Tim4-MyD88t-CD79b CER "CER89"

[0465] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a truncated MyD88 signaling domain (SEQ ID NO:78) and a secondary signaling domain comprising a CD79b signaling domain (SEQ ID NO:97) to create a chimeric engulfment receptor "CER89" (Tim4-MyD88t-CD79b CER having an amino acid sequence of SEQ ID NO:98). The MyD88t or CD79b signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MyD88t-CD79b (CER89) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 110). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MyD88t-CD79b (CER89) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 23

Construction of Tim4-MyD88t-NFAM1 CER "CER90"

[0466] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a truncated MyD88 signaling domain (SEQ ID NO:78) and a secondary signaling domain comprising a NFAM1 signaling domain (SEQ ID NO:92) to create a chimeric engulfment receptor "CER90" (Tim4-MyD88t-NFAM1 CER having an amino acid sequence of SEQ ID NO: 100). The MyD88t or NFAM1 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MyD88t-NFAM1 (CER90) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 111). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MyD88t-NFAM1 (CER90) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 24

Construction of Tim4-MyD88t-P2a-Rab5a CER "CER91"

[0467] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to a truncated MyD88 signaling domain (SEQ ID NO:78) to create a chimeric engulfment receptor "CER15". The MyD88t signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MyD88t (CER15) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with Rab5a and truncated EGFR as a transduction marker, separated by P2A sequence and T2A sequence, respectively (see, FIG. 112). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MyD88t-Rab5a (CER91, SEQ ID NO:105) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0468] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER91.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER91.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER91.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0469] The quantity of viable, CER91+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 113. The frequency of phagocytosis by CER91+Ba/F3 cells co-cultured with dexamethasone treated thymocytes was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 113A). Frequency of double positive staining cells for control Ba/F3 cells transduced with truncated EGFR and co-cultured with dexamethasone treated thymocytes is shown in FIG. 113B.

[0470] Fluorescent microscopy showed that CER91.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIG. 114). High magnification of an engulfment event is shown in the right of FIG. 114.

[0471] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIG. 115).

Example 25

Construction of Tim4-MERTK-MyD88 CER "CER92"

[0472] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a MERTK signaling domain (SEQ ID NO:69) and a secondary signaling domain comprising a truncated MyD88 signaling domain (SEQ ID NO:78) to create a chimeric engulfment receptor "CER92" (Tim4-MERTK-tMyD88 CER having an amino acid sequence of SEQ ID NO: 133). The MERTK or truncated MyD88 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MERTK-tMyD88t (CER92) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 116). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MERTK-tMyD88 (CER92) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0473] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER92.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER92.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER92.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0474] The quantity of viable, CER92+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 117. The frequency of phagocytosis by CER92+Ba/F3 cells was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 117A). Frequency of double positive staining cells for control Ba/F3 cells transduced with truncated EGFR and co-cultured with dexamethasone treated thymocytes is shown in FIG. 117B.

[0475] Fluorescent microscopy showed that CER92.sup.+ Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIG. 118). High magnification of an engulfment event is shown in the right of FIG. 118.

[0476] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIG. 119).

Example 26

Construction of TIM4-MERTK-BAFFR CER "CER93"

[0477] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a MERTK signaling domain (amino acid sequence of SEQ ID NO:43) and a secondary signaling domain comprising a BAFF-R (amino acid sequence of SEQ ID NO:94) to create a chimeric engulfment receptor "CER93" (Tim4-MERTK-BAFFR CER having an amino acid sequence of SEQ ID NO: 103). The MERTK or BAFF-R signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MERTK-BAFFR (CER93) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 120). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MERTK-BAFFR (CER93) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Phagocytic Activity Against Primary Apoptotic Thymocytes

[0478] Primary C3H mouse thymocytes were isolated, treated with dexamethasone, and stained with pHrodo Red as described in Example 8. Ba/F3 CER93.sup.+ tEGFR.sup.+ cells were labeled with CELLTRACE.TM. Violet dye as described in Example 8. Co-culture experiments with Ba/F3 CER93.sup.+ tEGFR.sup.+ cells and primary thymocytes were carried out at a 10:1 target cell to effector cell ratio, and Ba/F3 CER92.sup.+ EGFR.sup.+ cells were quantified for phagocytosis of target thymocytes by fluorescence microscopy and FACs as described in Example 8. Ba/F3 cells transduced with pLenti vector expressing truncated EGFR were used as a negative control.

[0479] The quantity of viable, CER93+ transduced Ba/F3 cells as quantified by FACS is shown in FIG. 121. The frequency of phagocytosis by CER93+Ba/F3 cells co-cultured with dexamethasone treated thymocytes was quantified as the cell population staining double positive for pHrodo Red and CELLTRACE Violet as detected by FACS (see, FIG. 121A). Frequency of double positive staining cells for control Ba/F3 cells transduced with truncated EGFR and co-cultured with dexamethasone treated thymocytes is shown in FIG. 121B.

[0480] Fluorescent microscopy showed that CER93+Ba/F3 cells engulf dexamethasone-treated thymocytes (white arrows indicate engulfment events) as compared to tEGFR transduced Ba/F3 control cells (see, FIG. 122). High magnification of an engulfment event is shown in the right of FIG. 122.

[0481] A phagocytic index was calculated by multiplying [mean of total number of engulfed target cells/total number of counted CER modified cells (e.g., phagocytic frequency)] by [average area of target cell staining per CER+ Ba/F3 cell.times.100 (e.g., hybrid capture)] as compared to EGFRt transduced Ba/F3 control cells (see, FIG. 123).

Example 27

Construction of Tim4-MERTK-DAP12 CER "CER94"

[0482] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a MERTK signaling domain (amino acid sequence of SEQ ID NO:43) and a secondary signaling domain comprising a DAP12 signaling domain (amino acid sequence of SEQ ID NO:82) to create a chimeric engulfment receptor "CER94" (Tim4-MERTK-DAP12 CER having an amino acid sequence of SEQ ID NO: 134). The MERTK or DAP12 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MERTK-DAP12 (CER94) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 124). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MERTK-DAP12 (CER94) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 28

Construction of Tim4-Axl-DAP12 CER "CER97"

[0483] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising an Axl signaling domain (SEQ ID NO:44) and a secondary signaling domain comprising a DAP12 signaling domain (SEQ ID NO:82) to create a chimeric engulfment receptor "CER97" (Tim4-AXL-DAP12 CER having an amino acid sequence of SEQ ID NO:152). The AXL or DAP12 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-AXL-DAP12 (CER97) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 125). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-AXL-DAP12 (CER97) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 29

Construction of Tim4-Axl-CD79b CER "CER98"

[0484] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising an Axl signaling domain (amino acid sequence of SEQ ID NO:44) and a secondary signaling domain comprising a CD79b signaling domain (amino acid sequence of SEQ ID NO:97) to create a chimeric engulfment receptor "CER98" (Tim4-AXL-CD79b CER having an amino acid sequence of SEQ ID NO: 153. The Axl or CD79b signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-AXL-CD79B (CER98) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 126). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-AXL-CD79b (CER98) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 30

Construction of Tim4-MERTK-CD79b CER "CER95"

[0485] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a MERTK signaling domain (amino acid sequence of SEQ ID NO:43) and a secondary signaling domain comprising a CD79b signaling domain (amino acid sequence of SEQ ID NO:97) to create a chimeric engulfment receptor "CER95" (Tim4-MERTK-CD79b CER having an amino acid sequence of SEQ ID NO: 101). The MERTK or CD79b signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MERTK-CD79b (CER95) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 127). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MERTK-CD79b (CER95) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 31

Construction of Tim4-MERTK-NFAM1 CER "CER96"

[0486] The extracellular domain of the phosphatidylserine binding protein Tim4 (amino acid sequence of SEQ ID NO:73), including the signal peptide (amino acid sequence of SEQ ID NO:72) and transmembrane domain (amino acid sequence of SEQ ID NO:74) were fused to primary signaling domain comprising a MERTK signaling domain (SEQ ID NO:43) and a secondary signaling domain comprising a NFAM1 signaling domain (SEQ ID NO:99) to create a chimeric engulfment receptor "CER96" (Tim4-MERTK-NFAM1 CER having an amino acid sequence of SEQ ID NO:102. The MERTK or NFAM1 signaling domain transduces a signal for engulfment, and Tim4 is a phosphatidylserine binding receptor. The Tim4-MERTK-NFAM1 (CER96) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence (see, FIG. 128). Murine Ba/F3 B-cells were transduced with pLenti vector expressing Tim4-MERTK-NFAM1 (CER96) and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

[0487] A variant of CER96 was also constructed, having an extracellular domain of the phosphatidylserine binding protein Tim4, including the signal peptide and transmembrane domain were fused to primary signaling domain comprising a MERTK signaling domain and a secondary signaling domain comprising a truncated NFAM1 signaling domain to create a chimeric engulfment receptor CER96t having an amino acid sequence of SEQ ID NO: 116.

Example 32

Construction of M912ScFv-IgG4-Tim4-MyD88t CER "CER50"

[0488] The extracellular domain comprising an scFv derived from mesothelin specific human monoclonal antibody M912 (Feng et al., 2009, Mol. Cancer Ther. 8:1113-1118) (amino acid sequence of SEQ ID NO: 106), including the signal peptide (amino acid sequence of SEQ ID NO:85) was fused to a modified IgG4 hinge region extracellular spacer domain (SEQ ID NO:67), a Tim4 transmembrane domain (amino acid sequence of SEQ ID NO:74) and a truncated MyD88 signaling domain (SEQ ID NO:69) to create a chimeric engulfment receptor "CER50" (M912scFv-IgG4-Tim4-MyD88t CER having an amino acid sequence of SEQ ID NO: 107. The MyD88t signaling domain transduces a signal for engulfment, and M912scFv binds to cell surface associated mesothelin. The M912scFv-IgG4-Tim4-MyD88t CER (CER50) chimeric engulfment receptor nucleotide sequence was then inserted into the pLenti lentiviral vector along with truncated EGFR as a transduction marker, separated by T2A sequence. Murine Ba/F3 B-cells were transduced with pLenti vector expressing M912scFv-IgG4-Tim4-MyD88t and EGFRt, expanded, sorted by FACs, and used for in vitro studies as described in Example 8.

Example 33

Compilation of In Vitro Phagocytosis Data

[0489] Phagocytosis data for CER+ modified Ba/F3 cells for various cell types performed as previously described were compiled. FIG. 129 shows phagocytic index for Ba/F3 cells modified with CER01, CER08, CER09, CER10, CER11, CER12, CER15, or EGFRt control co-cultured with dexamethasone treated primary thymocytes. FIG. 130 shows phagocytic index of Ba/F3 cells transduced with CER01, CER09, CER11, CER12, CER15, or EGFRt control co-cultured with staurosporine treated CT26 colon carcinoma cells. FIG. 131 shows phagocytic index of Ba/F3 cells transduced with CER01, CER09, CER11, CER12, CER15, or EGFRt control co-cultured with staurosporine treated A20 lymphoma cells.

Example 34

Phagocytic Activity of CER01 in Mouse Model of Lymphoma

[0490] A Tim4-MERTK CER nucleotide sequence encoding CER01 having an amino acid sequence of SEQ ID NO:71 (see also, FIG. 6A) was inserted into a pMSCV retroviral vector with a nucleotide sequence encoding green fluorescent protein (GFP). A timeline of a combination therapy regimen for radiation therapy and CER immunotherapy in a mouse model of lymphoma is shown in FIG. 132A.

[0491] 0.5.times.10.sup.6 38c13 mouse B-cell lymphoma cells were engrafted into NOD scid gamma (NSG) immunodeficient mice. Four days following engraftment, mice received 5 Gy of focal irradiation to the tumor site followed by intravenous injection of 6.times.10.sup.6 CER01+ transduced murine T cells (derived from C3H/HeN-MTV-negative mice). Tumor size was measured in two dimensions using precision calipers, and luciferase imaging was performed on day 4 following infusion of CER01+ transduced T cells. pMSCV empty retroviral vector transduced T cells were used as controls. As shown in the graph in FIG. 132B, CER modified T cells targeting phosphatidylserine synergized with low dose radiotherapy. In the photos shown in FIG. 132C, tumor growth was decreased in mice receiving combination therapy of CER modified T cells targeting phosphatidylserine and low dose radiation.

[0492] A timeline of an alternative combination therapy regimen for chimeric antigen receptor (CAR) immunotherapy and CER immunotherapy in a mouse model of lymphoma is shown in FIG. 133A. 0.5.times.10.sup.6 38c13 lymphoma cells were engrafted into NSG immunodeficient mice. Four days following engraftment, mice received an infusion of 5.times.10.sup.6 murine CD19-targeted CAR-T cells ("1D3 19z28" CAR having an anti-CD19 1D3 scFv, CD3-.zeta. cytoplasmic domain and CD28 cytoplasmic domain). Three days post-infusion of CAR modified T cells, 6.times.10.sup.6 CER01+ transduced T cells were infused in the mice. Tumor size was measured in two dimensions using precision calipers, and luciferase imaging performed on day 4 following infusion of CER01+ transduced T cells or CER01+ transduced B cells (see photos shown in bottom of FIG. 133B). pMSCV empty retroviral vector transduced T cells were used as controls. As shown in FIG. 133B, CER+ T cells or CER+ B cells targeting PtdSer.sup.+ synergized with low dose CAR modified T cell therapy.

[0493] The various embodiments described above can be combined to provide further embodiments. All of the U.S. patents, U.S. patent application publications, U.S. patent applications, foreign patents, foreign patent applications and non-patent publications referred to in this specification and/or listed in the Application Data Sheet including U.S. Patent Application No. 62/400,578 filed on Sep. 27, 2016, and U.S. Patent Application No. 62/445,235, filed on Jan. 11, 2017, are incorporated herein by reference, in their entireties. Aspects of the embodiments can be modified, if necessary to employ concepts of the various patents, applications and publications to provide yet further embodiments.

[0494] These and other changes can be made to the embodiments in light of the above-detailed description. In general, in the following claims, the terms used should not be construed to limit the claims to the specific embodiments disclosed in the specification and the claims, but should be construed to include all possible embodiments along with the full scope of equivalents to which such claims are entitled. Accordingly, the claims are not limited by the disclosure.

Sequence CWU 1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 153 <210> SEQ ID NO 1 <211> LENGTH: 870 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 binding domain <400> SEQUENCE: 1 atgcaccccc aggttgttat actttcattg atcctgcatt tggccgactc cgtggcgggt 60 tccgtaaaag ttggagggga agctggacca agcgtcacct tgccttgcca ctactctgga 120 gccgtgacga gtatgtgctg gaatcgagga tcctgtagtc ttttcacatg ccaaaatggc 180 atagtttgga ccaatgggac gcacgtcacc taccgaaaag acactagata caaactcctg 240 ggtgacctca gcaggagaga tgtgtctctg actattgaaa acactgctgt ttctgactct 300 ggagtctact gttgccgggt cgagcaccga ggatggttca atgacatgaa gatcacggtc 360 agcttggaaa tcgtcccgcc caaggtaacc actacaccaa tagttactac ggttcccacg 420 gtaaccacgg ttcgaaccag caccacagta cccacaacta cgaccgttcc aaccactaca 480 gtccccacaa ccatgagtat ccctacgaca actacggtcc tgacaaccat gaccgtcagc 540 actaccacga gtgtgcctac gactactagc ataccgacga ctacttcagt tccagtcacc 600 accacggtga gtacattcgt gcctccaatg ccattgccga ggcaaaacca cgaacccgtg 660 gcgacatctc cgtctagtcc gcaaccagca gagacccatc ccaccacgct tcagggggca 720 atcaggagag aacctacaag ttcacccctc tacagctata caaccgatgg aaacgacaca 780 gttacagaaa gtagtgacgg tttgtggaat aacaaccaaa cacaattgtt cctggagcac 840 agtctgttga cagccaacac tacaaaggga 870 <210> SEQ ID NO 2 <211> LENGTH: 942 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain <400> SEQUENCE: 2 atgagtaaag agccgcttat cctgtggctt atgatagagt tttggtggtt gtatttgacc 60 ccggtcacga gcgaaacggt agtgactgaa gtattgggtc atcgggtaac cttgccttgc 120 ttgtatagct cctggtctca taatagtaat agcatgtgct ggggcaagga ccaatgcccc 180 tatagcggat gcaaggaggc gctcattcgc acagacggaa tgcgggtgac atcaaggaag 240 agtgctaagt accggcttca gggcacaatc ccacgcggcg acgtgtcact gactatcctt 300 aatccatccg agagcgactc tggtgtctat tgttgcagga tcgaggttcc gggatggttc 360 aatgatgtaa agatcaatgt aagactcaat ctgcaacggg catctacaac cacgcatcgg 420 acagccacta ctaccacaag gagaacaact actacgtcac ccacgactac tcgacagatg 480 accactacac ctgcggccct gccaactacg gttgtaacta ctccggatct gacaaccggg 540 acaccgttgc aaatgacaac cattgcagta tttaccacgg caaacacgtg tctctctctg 600 accccatcta ctcttccgga ggaggccacc gggctcctta caccggagcc gtctaaggaa 660 ggcccaatct tgaccgcaga gagtgagacc gtacttccga gcgattcatg gtccagtgtc 720 gagagcacat ccgctgacac cgtccttctt acgtccaaag aaagtaaagt ttgggacctc 780 ccgtccacga gccacgtttc tatgtggaag acctcagata gcgttagctc cccacagcca 840 ggagcaagcg acaccgcagt accggagcaa aacaagacga ctaagactgg ccagatggat 900 ggtatcccaa tgtcaatgaa aaatgagatg cccatatcac aa 942 <210> SEQ ID NO 3 <211> LENGTH: 483 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FA58C2 binding domain <400> SEQUENCE: 3 ctcaacgggt gtgctaatcc ccttggcctg aagaataaca gcatacctga caagcaaata 60 acagcgtcaa gttcttataa aacttggggg ctgcatctgt tctcctggaa ccccagttac 120 gctagactcg acaaacaagg caattttaac gcatgggtgg caggctctta cgggaacgat 180 cagtggctgc aagtagactt gggaagtagt aaggaggtga ctgggatcat tacccagggg 240 gcacgaaatt tcggttccgt tcagttcgtt gcatcttata aggtagcgta ttcaaatgac 300 tccgcgaatt ggaccgaata tcaggacccg cgaaccggat caagcaagat ttttccgggg 360 aattgggaca accactctca caaaaaaaat ttgtttgaaa cacctatact ggcgcggtac 420 gttagaatcc tcccagttgc ctggcacaac cggatagcgc ttagactgga attgttgggg 480 tgc 483 <210> SEQ ID NO 4 <211> LENGTH: 876 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI binding domain <400> SEQUENCE: 4 atgtggttcc tgactacgtt gttgctgtgg gtccctgtag acggccaagt agacacaacg 60 aaagcagtga tcacgctcca accgccttgg gtgtctgtgt tccaagaaga aacagttaca 120 ctgcactgtg aggtcctcca cctgcctggt tcttcatcta ctcaatggtt tctcaacgga 180 acagcaacac aaacaagtac cccttcctac agaattacga gtgcatctgt taacgattca 240 ggagagtata ggtgccagcg agggctttca ggccggtccg accccattca actcgaaatt 300 caccgcggtt ggcttctgct gcaagtatcc tctcgggtct tcacggaagg tgaaccactt 360 gccttgcgct gtcacgcatg gaaagataag ctcgtctaca acgttttgta ttatcggaat 420 ggaaaggcat ttaagttttt tcattggaac tcaaacctta cgatcctcaa aaccaatatc 480 agtcataacg gtacgtacca ctgctcaggc atgggcaagc atcgctatac gtccgcaggg 540 attagcgtga cagttaagga gctcttcccc gcgcctgtgc tgaatgcgag cgtaacttca 600 ccccttctgg agggcaactt ggtgaccctc tcttgtgaga cgaaacttct ccttcagagg 660 ccgggcctgc aactctattt cagcttttat atgggttcta aaactcttcg aggcagaaac 720 acgagcagcg aatatcagat actgactgcc cggcgggaag acagtggcct ttattggtgc 780 gaggctgcaa cagaagatgg caatgtcctt aaaaggtctc ccgaattgga gctccaagtg 840 cttggcttgc aactccctac acccgtatgg ttccac 876 <210> SEQ ID NO 5 <211> LENGTH: 282 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: GAS6 binding domain <400> SEQUENCE: 5 atggctccct ctttgtcacc aggacctgcg gctcttaggc gagccccgca gctgctgctt 60 ctcctgctcg ctgcagaatg cgctctcgct gcactcttgc ccgcgaggga ggcgactcag 120 ttcttgcgcc cccggcagag acgagcattc caagtctttg aggaagcgaa acaaggtcat 180 ctcgagcgag aatgcgtgga ggagctgtgt tctagggagg aagcacgcga agtctttgag 240 aatgacccgg aaacggacta cttttacccc cggtatcttg at 282 <210> SEQ ID NO 6 <211> LENGTH: 261 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Protein S binding domain <400> SEQUENCE: 6 atgcgcgtgt tggggggtcg ctgtggtgcg ctccttgctt gtctcctttt ggttcttccc 60 gtctccgagg ctaatttcct gtcaaaacaa caggctagtc aagtcttggt gcgcaagagg 120 agagctaaca gccttctgga agagaccaag caaggtaatc tggagagaga gtgtatcgag 180 gaactttgta acaaagagga agcacgcgaa gtatttgaaa atgacccgga aaccgattat 240 ttttacccaa aatatctcgt a 261 <210> SEQ ID NO 7 <211> LENGTH: 606 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim3 binding domain <400> SEQUENCE: 7 atgtttagcc atctcccttt tgattgcgtc ttgttgcttc ttcttctcct tctgacgaga 60 tcatctgaag ttgaatatcg cgcggaagtc ggccaaaacg catatctgcc gtgtttttac 120 accccggctg caccggggaa cttggttccc gtttgttggg gtaagggggc gtgtcccgtt 180 tttgagtgcg gtaacgtagt gctccgaact gatgaaagag atgtaaatta ctggacgagc 240 cggtactggt tgaatgggga ttttaggaag ggcgacgttt cccttaccat agaaaacgta 300 actcttgcgg attctgggat ttattgttgc aggatacaaa tccccggaat aatgaacgat 360 gagaaattca atttgaagct cgtaataaaa ccggcaaaag taactccagc tcccaccagg 420 cagcgagatt ttacggcagc atttcccagg atgctcacta ctcgcggtca tggccctgcc 480 gagactcaga ccctcggtag tcttcctgat atcaatctca cgcaaattag tacattggcg 540 aatgaattga gggattcaag actcgccaat gatctgcgcg acagtggagc gactattagg 600 ataggg 606 <210> SEQ ID NO 8 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 transmembrane domain <400> SEQUENCE: 8 atatacgctg gagtctgtat aagtgtcctt gtactgttgg cgttgctggg ggtcattatt 60 gcc 63 <210> SEQ ID NO 9 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 transmembrane domain <400> SEQUENCE: 9 ttgcttatga ttattgcgcc aagccttgga tttgtgctgt tcgcactctt cgtagctttt 60 ctc 63 <210> SEQ ID NO 10 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI transmembrane domain <400> SEQUENCE: 10 gtactgtttt atctcgccgt agggataatg ttcctcgtga acaccgtact gtgggtaaca 60 ata 63 <210> SEQ ID NO 11 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD8a transmembrane domain <400> SEQUENCE: 11 atatacattt gggcaccgct ggctggaact tgcggcgttc tcttgttgag tctggtgatt 60 act 63 <210> SEQ ID NO 12 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK transmembrane domain <400> SEQUENCE: 12 tttggctgtt tctgtggatt tattctgatt ggtcttatcc tctatatttc cttggcgatc 60 aga 63 <210> SEQ ID NO 13 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl transmembrane domain <400> SEQUENCE: 13 tatgtcttgc ttggtgccgt cgttgctgcc gcctgtgtgt tgatactcgc acttttcttg 60 gtg 63 <210> SEQ ID NO 14 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 transmembrane domain <400> SEQUENCE: 14 gtacccgtcg ttttgggggt cctgaccgcg ctcgttactg cggcagcact cgcactgata 60 ctt 63 <210> SEQ ID NO 15 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD4 transmembrane domain <400> SEQUENCE: 15 atggctctga tcgtactggg cggagtggca ggattgctgc tctttattgg actgggcatt 60 ttcttc 66 <210> SEQ ID NO 16 <211> LENGTH: 1428 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 16 gcgctgcggc gaagggtaca ggagacgaaa ttcgggggag cctttagtga agaagacagc 60 cagttggtgg taaattacag agcgaaaaaa tctttctgcc gacgcgctat tgagcttact 120 cttcaaagcc tcggtgtaag tgaggagttg cagaataaat tggaggacgt agtcatcgac 180 cgcaaccttc tggtcctcgg aaaagtcctc ggagaaggtg aattcggctc agtaatggaa 240 ggcaatctca aacaagaaga cggaacttct cagaaggtag cagtaaaaac catgaaactc 300 gacaacttca gccagcggga aatcgaagaa ttcctgtccg aagccgcctg tatgaaagac 360 ttcaatcacc caaacgtgat aagacttctc ggcgtatgta tagagttgtc ttcccagggc 420 atccccaaac caatggtgat actcccattt atgaagtacg gggacttgca cacattcctg 480 ttgtattcca gacttaatac aggacccaag tatatacatt tgcagaccct gctcaaattt 540 atgatggaca tcgcgcaggg gatggagtat ctcagcaaca ggaatttttt gcatcgcgac 600 cttgctgcca ggaactgtat gttgagggac gacatgacgg tgtgtgtagc cgacttcggt 660 cttagcaaga agatctattc tggagactat tacaggcaag gcagaatagc taagatgccg 720 gtcaagtgga tcgctattga gagcctcgca gaccgggtct atacttcaaa gtcagacgtt 780 tgggcttttg gggtaaccat gtgggagatc actacgaggg ggatgacgcc ctatcccggg 840 gtccaaaatc acgagatgta tgattatctc ttgcatggcc accggctgaa acagcctgag 900 gactgtctgg acgagctcta cgatattatg tattcttgtt ggtccgcgga ccccctcgat 960 agaccaacct tttctgttct tcgactgcag ctcgaaaagc tttccgaatc tttgcctgat 1020 gcacaggaca aagaaagcat catttatata aatacacagc tcctggaatc ttgcgaagga 1080 attgctaatg gacctagtct gactggattg gacatgaata ttgacccgga cagcataatt 1140 gcatcttgca cacctggtgc agcggtatca gtcgtgacgg ccgaggtcca tgaaaacaat 1200 ctgcgggagg agcggtacat tttgaacggc ggaaacgaag agtgggagga cgtcagctca 1260 accccctttg cagccgtgac gccagagaaa gacggggtac ttcctgagga ccgccttacc 1320 aagaacgggg tatcctggtc tcaccacagc accctcccac ttgggagtcc atctcccgac 1380 gagcttctct tcgtagatga ttcacttgaa gattcagagg tgctcatg 1428 <210> SEQ ID NO 17 <211> LENGTH: 1266 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl signaling domain <400> SEQUENCE: 17 caccggagaa aaaaagagac ccgctacgga gaggtctttg agcctacggt cgagagaggt 60 gagcttgttg tccggtacag agtgaggaag agctattcac ggaggactac tgaagccacc 120 ctgaattcac tcggcatcag cgaagagctg aaagagaaac ttcgggacgt aatggtcgat 180 cggcacaagg tagccctcgg gaagacgttg ggagagggcg aatttggggc cgtcatggag 240 ggtcagttga accaagatga ctcaatactt aaagtagcag tcaaaacgat gaaaatcgca 300 atttgtactc gctcagagct cgaagacttt ctctctgagg cggtatgcat gaaggaattc 360 gaccacccaa atgtaatgcg attgatcggt gtctgcttcc aaggttccga aagagagtca 420 tttcctgcac ccgttgtcat tttgccattt atgaagcatg gggacctcca ctcatttctc 480 ctctattcta gattgggtga ccaaccggtt tacctcccga cccaaatgct cgttaagttc 540 atggccgaca ttgcttccgg gatggagtac ctgagtacca agcggtttat acatcgggat 600 ctcgcagcac gaaactgcat gttgaatgag aacatgtctg tctgtgtggc tgactttgga 660 ctctccaaaa aaatttacaa cggtgattat taccgccagg gaagaatcgc taagatgccc 720 gtgaagtgga tagctattga gtcactcgct gatcgcgtat acactagtaa gtccgacgta 780 tggtcctttg gtgtcacaat gtgggagatt gcgaccaggg ggcagacacc atatcccggc 840 gtggagaact ccgagattta tgattatctg cgacagggta acagacttaa gcaacctgcc 900 gattgcttgg atgggctcta cgctctgatg tctagatgct gggaattgaa tcctcaagat 960 cggccaagct tcactgaact gagagaagac ctggaaaata ccctgaaagc gctcccgccg 1020 gcgcaagaac cagatgaaat cttgtacgtc aatatggacg aagggggagg ctaccctgaa 1080 ccccctgggg cggccggtgg ggcggacccc ccgacacaac cagatccgaa agactcctgt 1140 tcttgtctta ccgctgctga ggtacatccg gcaggaagat atgttttgtg tccctctacg 1200 acaccctctc ccgcacagcc cgcggatcgc gggtcacccg cggctccagg acaagaagat 1260 ggggca 1266 <210> SEQ ID NO 18 <211> LENGTH: 1320 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 signaling domain <400> SEQUENCE: 18 ttgcggaagc ggcgaaagga aaccagattc ggtcaagctt tcgacagcgt aatggcccgg 60 ggtgagccag ccgtccactt tagagccgct cggagcttca atagggaacg accggagaga 120 atcgaggcta ctctcgattc tctcggaata tctgacgagt tgaaagaaaa actggaggat 180 gtcctcatcc cagaacaaca atttaccctc ggccgaatgc ttggaaaggg tgagtttggg 240 tcagttcgcg aggcgcagct taaacaggaa gacggtagtt ttgttaaagt cgcagtaaaa 300 atgttgaagg cggacataat cgcatccagc gatattgagg aatttcttcg cgaagcggca 360 tgtatgaaag agttcgacca cccgcacgtt gccaagctcg tgggcgtgtc tcttcgaagc 420 cgagctaagg gtagactccc tatcccaatg gtaatacttc cttttatgaa acatggggac 480 ttgcacgctt ttctgctcgc ttccaggata ggagaaaatc cgtttaattt gccgctccaa 540 acgcttatca ggtttatggt tgatattgcg tgtgggatgg aatacttgag ttcacgcaat 600 ttcatccatc gagacctggc cgcgcgaaat tgtatgctcg cagaggatat gaccgtatgt 660 gtagctgatt tcggcttgtc acgcaagata tatagcggcg attattatag acagggttgt 720 gcctctaagc tccctgtaaa gtggttggca ttggaatcac tggcggataa cctctatact 780 gtccagtcag atgtgtgggc atttggtgtc actatgtggg agattatgac acggggtcag 840 acaccctacg caggaatcga gaacgcggag atatataact acctgatagg tggcaaccga 900 ctgaaacaac ctccggaatg catggaggac gtgtatgacc tcatgtacca gtgttggagt 960 gccgatccga aacaaagacc tagtttcact tgcctgagaa tggagttgga gaatattttg 1020 ggtcagttgt ccgtactgag cgccagccaa gatccgttgt atataaatat agagcgggcg 1080 gaggagccca cggccggcgg gtccctggaa cttcctggac gagaccaacc gtactcaggg 1140 gccggagatg gaagtggaat gggggctgtt gggggcacac cgtccgactg ccgatacata 1200 ctcactccgg gcggtctcgc agaacaaccg ggtcaagcag aacatcaacc agaaagtcca 1260 ctcaatgaga cacagcgact gttgttgttg caacagggct tgctgcctca ctcatcctgt 1320 <210> SEQ ID NO 19 <211> LENGTH: 783 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Syk signaling domain <400> SEQUENCE: 19 acattggaag acaaagaact ggggtctggg aacttcggga cagtcaaaaa ggggtactac 60 cagatgaaaa aagttgtcaa aactgtggcg gtaaaaatct tgaaaaatga agctaatgac 120 cctgcactca aggatgagct tctggcagaa gctaacgtga tgcagcagct tgataatcct 180 tatattgttc gcatgatagg tatatgtgag gcggaaagct ggatgctcgt aatggaaatg 240 gcagaactgg gaccattgaa taaatatctg caacaaaata gacatgtgaa ggataaaaac 300 atcatagagc tcgtacacca agtctctatg gggatgaagt acttggagga gagcaacttc 360 gtgcataggg acttggccgc ccgaaacgta ctgctcgtaa ctcaacatta cgcgaaaatc 420 tcagacttcg gtttgtctaa agcactccgg gcagacgaga actactacaa agcccaaact 480 cacggcaagt ggccagtcaa gtggtacgcg ccggaatgca taaactatta caagtttagt 540 tctaagtctg atgtgtggag cttcggggtt ctgatgtggg aagcctttag ttatggacag 600 aagccctacc gggggatgaa aggaagcgag gtaacagcta tgctggaaaa aggggagcgg 660 atgggctgtc cagcggggtg tcctcgagaa atgtatgatc tcatgaacct gtgttggacc 720 tacgatgtcg agaatcgccc gggctttgct gcggtggaac ttagactgag gaattattac 780 tac 783 <210> SEQ ID NO 20 <211> LENGTH: 789 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Zap70 signaling domain <400> SEQUENCE: 20 ctcattgccg acatcgaact tggttgcggc aacttcggat ctgtgagaca aggcgtctac 60 cggatgagaa agaagcagat tgacgttgca atcaaagtcc tgaagcaggg cacggaaaag 120 gcggacaccg aggagatgat gcgcgaggct cagattatgc accagctcga caatccgtac 180 atcgttagac ttatcggagt ttgccaggca gaagcgttga tgctcgtgat ggagatggca 240 ggcggtggtc ctctgcataa atttttggta ggcaagcgag aagagatccc cgtcagcaat 300 gtagcagaat tgttgcatca agtgagcatg gggatgaagt accttgagga aaaaaatttc 360 gtacatcgcg acctcgctgc gagaaatgtg cttttggtaa atcgccatta cgctaaaatt 420 agtgactttg gactcagtaa ggcattgggt gctgacgact catattacac ggcaagaagc 480 gcaggtaagt ggcctctgaa gtggtatgct cccgagtgca tcaacttccg caagttttct 540 tccaggtctg acgtttggag ctacggtgtc acgatgtggg aagccctgag ctatggtcag 600 aaaccttaca agaaaatgaa gggacctgaa gtcatggcct ttatagagca gggaaagaga 660 atggagtgtc ccccagaatg cccacccgag ctctatgcac tgatgagtga ctgctggatt 720 tacaaatggg aggatcggcc tgactttctt acggttgagc aaaggatgag ggcgtgctat 780 tattctctg 789 <210> SEQ ID NO 21 <211> LENGTH: 183 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI signaling domain <400> SEQUENCE: 21 agaaaggaac tcaagcgcaa gaagaagtgg gacctggaga tttctctcga ctccggtcac 60 gaaaagaagg tcatcagtag cttgcaagag gaccgacact tggaagaaga acttaaatgc 120 caggaacaga aagaggagca gctccaggag ggagtccacc ggaaagaacc acagggagca 180 act 183 <210> SEQ ID NO 22 <211> LENGTH: 231 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2A signaling domain <400> SEQUENCE: 22 tgtcgaaaga agcggatttc agccaatagt acagacccag tgaaagccgc tcaatttgag 60 ccacccggtc gacagatgat cgcaattagg aaacgccaac tggaggaaac gaataatgat 120 tacgaaacgg cagatggggg ctacatgacg ctcaatccta gagctccgac cgacgacgac 180 aagaatatat atctgactct ccctcccaac gaccacgtaa acagtaataa c 231 <210> SEQ ID NO 23 <211> LENGTH: 231 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2C signaling domain <400> SEQUENCE: 23 tgcagaaaga agcggataag tgcaaatagt actgatcccg ttaaagcagc acaatttgag 60 ccgccaggac ggcaaatgat tgcaatcaga aaacgacaac ccgaggaaac caataatgac 120 tacgagaccg ctgacggagg gtatatgacg ttgaatcccc gcgcaccaac ggatgacgat 180 aagaacattt atcttacgct gccccctaac gatcatgtga atagcaataa c 231 <210> SEQ ID NO 24 <211> LENGTH: 75 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR3A signaling domain <400> SEQUENCE: 24 aaaacaaata tccggtcctc tacgagggac tggaaagatc ataaattcaa gtggagaaaa 60 gatcctcagg ataaa 75 <210> SEQ ID NO 25 <211> LENGTH: 168 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 25 aagttgcttg taacaataca cgaccgccgg gagttcgcta agttccaatc agaaaggtct 60 agagcgcggt atgaaatggc atctaacccc ttgtaccgga aacctatctc tacgcacacg 120 gtggatttcg catttaataa gttcaataag agttacaacg gctcagtc 168 <210> SEQ ID NO 26 <211> LENGTH: 888 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MyD88 signaling domain <400> SEQUENCE: 26 atggccgcgg gtggacccgg tgcagggtct gccgcaccgg tgtctagcac cagctcactg 60 ccgctggcag cgttgaacat gagggtaaga agacggctta gtcttttctt gaatgtgcga 120 acgcaggtgg ccgctgactg gacggccctc gctgaggaaa tggacttcga gtacctggag 180 atccggcaac tcgagactca agccgaccct actggaagat tgctcgatgc ctggcaggga 240 aggcccggcg catcagttgg taggttgttg gaactcctca ccaaactcgg gcgagatgat 300 gttcttttgg aacttggccc tagtattgag gaggactgtc aaaaatatat tctgaaacaa 360 caacaggaag aagcggagaa accgttgcaa gtggccgcag tcgattcttc agtgccgcgc 420 acagccgaac tggctggaat tactaccctg gatgatcccc tcggacacat gccggagcgg 480 ttcgacgcct tcatttgcta ttgtccctcc gacatccagt ttgtgcagga aatgattagg 540 caactcgaac aaaccaacta taggcttaaa ctgtgtgtgt ccgatcgaga tgttttgcct 600 ggtacttgcg tatggtctat tgccagcgaa ctcatagaga aacgctgtcg ccgcatggta 660 gtggtcgtat ccgacgacta ccttcagtcc aaagagtgtg acttccagac gaaatttgca 720 ctgtcactga gtcctggagc acaccaaaaa aggctgattc cgatcaagta taaggcgatg 780 aagaaggaat ttccttccat cctgaggttc ataactgtat gcgattacac aaatccgtgt 840 actaaatcct ggttctggac tcgacttgcc aaggcactgt ccctccca 888 <210> SEQ ID NO 27 <211> LENGTH: 1566 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Traf6 signaling domain <400> SEQUENCE: 27 atgtcactcc ttaactgcga aaacagttgt gggagttcac aatccgaaag tgattgttgc 60 gtggcgatgg cgtcttcatg ctctgcggtt accaaggatg actctgtggg aggcaccgca 120 tctaccggaa atctgagctc ttcttttatg gaggaaattc agggctacga cgttgagttt 180 gatcctcctc tcgaatctaa gtatgagtgc cccatatgtc tcatggcgtt gagagaagca 240 gtgcagactc cgtgcggaca tcgcttctgc aaggcgtgta ttataaagag tatacgcgat 300 gcgggtcaca aatgtccagt ggacaacgag atactgcttg aaaatcaact tttccccgac 360 aattttgcaa agagagagat actgtctttg atggttaagt gtccaaacga gggctgcttg 420 cacaaaatgg aactccgaca ccttgaagac caccaggcac actgcgagtt cgccctcatg 480 gattgcccac aatgccagcg cccgttccaa aagtttcaca taaacatcca catactgaag 540 gactgtccta ggagacaagt aagctgtgac aattgcgcag cgtcaatggc gttcgaggac 600 aaggagatac acgatcaaaa ctgtcctctg gcgaatgtga tctgcgaata ttgcaatacg 660 atcttgatcc gcgaacagat gcctaatcat tacgacctcg attgtccgac cgcgccaatt 720 ccttgtactt tttctacctt cggatgtcat gagaaaatgc aacgaaatca cctggctcgc 780 catcttcagg agaatactca gagccacatg cgcatgttgg ctcaagccgt acatagcctt 840 agcgtaatac cggactcagg ttatatatcc gaagtacgga attttcaaga aaccatacat 900 caacttgaag gaaggttggt acgacaggat catcagatac gcgaattgac ggccaagatg 960 gaaacccaga gcatgtatgt cagtgagctt aagcgcacta tccgaaccct ggaggataaa 1020 gttgccgaaa tcgaagctca acaatgcaac gggatataca tttggaaaat aggtaacttc 1080 ggaatgcacc tgaagtgtca agaagaagaa aaacctgtcg ttattcattc ccccggcttt 1140 tatacaggga agcctgggta taagctttgc atgaggctcc acctccaatt gccgacggcg 1200 caaaggtgcg caaattacat ttctctgttt gtccatacta tgcagggtga gtacgatagt 1260 cacttgccgt ggcccttcca gggtaccata cgattgacca tcctggatca gagcgaggcc 1320 cccgtgcgac agaatcatga agaaataatg gatgctaagc cggaactgct cgctttccag 1380 agacctacaa ttccgcgaaa tcctaagggt tttggctatg ttacgttcat gcatctggaa 1440 gcactcagac aaagaacatt cattaaagat gacaccttgc ttgtgcggtg tgaggtgtca 1500 accaggttcg acatgggatc tctcagacgg gaggggttcc aaccgcgctc tacagacgct 1560 ggagtg 1566 <210> SEQ ID NO 28 <211> LENGTH: 290 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(20) <400> SEQUENCE: 28 Met His Pro Gln Val Val Ile Leu Ser Leu Ile Leu His Leu Ala Asp 1 5 10 15 Ser Val Ala Gly Ser Val Lys Val Gly Gly Glu Ala Gly Pro Ser Val 20 25 30 Thr Leu Pro Cys His Tyr Ser Gly Ala Val Thr Ser Met Cys Trp Asn 35 40 45 Arg Gly Ser Cys Ser Leu Phe Thr Cys Gln Asn Gly Ile Val Trp Thr 50 55 60 Asn Gly Thr His Val Thr Tyr Arg Lys Asp Thr Arg Tyr Lys Leu Leu 65 70 75 80 Gly Asp Leu Ser Arg Arg Asp Val Ser Leu Thr Ile Glu Asn Thr Ala 85 90 95 Val Ser Asp Ser Gly Val Tyr Cys Cys Arg Val Glu His Arg Gly Trp 100 105 110 Phe Asn Asp Met Lys Ile Thr Val Ser Leu Glu Ile Val Pro Pro Lys 115 120 125 Val Thr Thr Thr Pro Ile Val Thr Thr Val Pro Thr Val Thr Thr Val 130 135 140 Arg Thr Ser Thr Thr Val Pro Thr Thr Thr Thr Val Pro Thr Thr Thr 145 150 155 160 Val Pro Thr Thr Met Ser Ile Pro Thr Thr Thr Thr Val Leu Thr Thr 165 170 175 Met Thr Val Ser Thr Thr Thr Ser Val Pro Thr Thr Thr Ser Ile Pro 180 185 190 Thr Thr Thr Ser Val Pro Val Thr Thr Thr Val Ser Thr Phe Val Pro 195 200 205 Pro Met Pro Leu Pro Arg Gln Asn His Glu Pro Val Ala Thr Ser Pro 210 215 220 Ser Ser Pro Gln Pro Ala Glu Thr His Pro Thr Thr Leu Gln Gly Ala 225 230 235 240 Ile Arg Arg Glu Pro Thr Ser Ser Pro Leu Tyr Ser Tyr Thr Thr Asp 245 250 255 Gly Asn Asp Thr Val Thr Glu Ser Ser Asp Gly Leu Trp Asn Asn Asn 260 265 270 Gln Thr Gln Leu Phe Leu Glu His Ser Leu Leu Thr Ala Asn Thr Thr 275 280 285 Lys Gly 290 <210> SEQ ID NO 29 <211> LENGTH: 314 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(24) <400> SEQUENCE: 29 Met Ser Lys Glu Pro Leu Ile Leu Trp Leu Met Ile Glu Phe Trp Trp 1 5 10 15 Leu Tyr Leu Thr Pro Val Thr Ser Glu Thr Val Val Thr Glu Val Leu 20 25 30 Gly His Arg Val Thr Leu Pro Cys Leu Tyr Ser Ser Trp Ser His Asn 35 40 45 Ser Asn Ser Met Cys Trp Gly Lys Asp Gln Cys Pro Tyr Ser Gly Cys 50 55 60 Lys Glu Ala Leu Ile Arg Thr Asp Gly Met Arg Val Thr Ser Arg Lys 65 70 75 80 Ser Ala Lys Tyr Arg Leu Gln Gly Thr Ile Pro Arg Gly Asp Val Ser 85 90 95 Leu Thr Ile Leu Asn Pro Ser Glu Ser Asp Ser Gly Val Tyr Cys Cys 100 105 110 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Ile Asn Val Arg 115 120 125 Leu Asn Leu Gln Arg Ala Ser Thr Thr Thr His Arg Thr Ala Thr Thr 130 135 140 Thr Thr Arg Arg Thr Thr Thr Thr Ser Pro Thr Thr Thr Arg Gln Met 145 150 155 160 Thr Thr Thr Pro Ala Ala Leu Pro Thr Thr Val Val Thr Thr Pro Asp 165 170 175 Leu Thr Thr Gly Thr Pro Leu Gln Met Thr Thr Ile Ala Val Phe Thr 180 185 190 Thr Ala Asn Thr Cys Leu Ser Leu Thr Pro Ser Thr Leu Pro Glu Glu 195 200 205 Ala Thr Gly Leu Leu Thr Pro Glu Pro Ser Lys Glu Gly Pro Ile Leu 210 215 220 Thr Ala Glu Ser Glu Thr Val Leu Pro Ser Asp Ser Trp Ser Ser Val 225 230 235 240 Glu Ser Thr Ser Ala Asp Thr Val Leu Leu Thr Ser Lys Glu Ser Lys 245 250 255 Val Trp Asp Leu Pro Ser Thr Ser His Val Ser Met Trp Lys Thr Ser 260 265 270 Asp Ser Val Ser Ser Pro Gln Pro Gly Ala Ser Asp Thr Ala Val Pro 275 280 285 Glu Gln Asn Lys Thr Thr Lys Thr Gly Gln Met Asp Gly Ile Pro Met 290 295 300 Ser Met Lys Asn Glu Met Pro Ile Ser Gln 305 310 <210> SEQ ID NO 30 <211> LENGTH: 161 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FA58C2 binding domain <400> SEQUENCE: 30 Leu Asn Gly Cys Ala Asn Pro Leu Gly Leu Lys Asn Asn Ser Ile Pro 1 5 10 15 Asp Lys Gln Ile Thr Ala Ser Ser Ser Tyr Lys Thr Trp Gly Leu His 20 25 30 Leu Phe Ser Trp Asn Pro Ser Tyr Ala Arg Leu Asp Lys Gln Gly Asn 35 40 45 Phe Asn Ala Trp Val Ala Gly Ser Tyr Gly Asn Asp Gln Trp Leu Gln 50 55 60 Val Asp Leu Gly Ser Ser Lys Glu Val Thr Gly Ile Ile Thr Gln Gly 65 70 75 80 Ala Arg Asn Phe Gly Ser Val Gln Phe Val Ala Ser Tyr Lys Val Ala 85 90 95 Tyr Ser Asn Asp Ser Ala Asn Trp Thr Glu Tyr Gln Asp Pro Arg Thr 100 105 110 Gly Ser Ser Lys Ile Phe Pro Gly Asn Trp Asp Asn His Ser His Lys 115 120 125 Lys Asn Leu Phe Glu Thr Pro Ile Leu Ala Arg Tyr Val Arg Ile Leu 130 135 140 Pro Val Ala Trp His Asn Arg Ile Ala Leu Arg Leu Glu Leu Leu Gly 145 150 155 160 Cys <210> SEQ ID NO 31 <211> LENGTH: 292 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(15) <400> SEQUENCE: 31 Met Trp Phe Leu Thr Thr Leu Leu Leu Trp Val Pro Val Asp Gly Gln 1 5 10 15 Val Asp Thr Thr Lys Ala Val Ile Thr Leu Gln Pro Pro Trp Val Ser 20 25 30 Val Phe Gln Glu Glu Thr Val Thr Leu His Cys Glu Val Leu His Leu 35 40 45 Pro Gly Ser Ser Ser Thr Gln Trp Phe Leu Asn Gly Thr Ala Thr Gln 50 55 60 Thr Ser Thr Pro Ser Tyr Arg Ile Thr Ser Ala Ser Val Asn Asp Ser 65 70 75 80 Gly Glu Tyr Arg Cys Gln Arg Gly Leu Ser Gly Arg Ser Asp Pro Ile 85 90 95 Gln Leu Glu Ile His Arg Gly Trp Leu Leu Leu Gln Val Ser Ser Arg 100 105 110 Val Phe Thr Glu Gly Glu Pro Leu Ala Leu Arg Cys His Ala Trp Lys 115 120 125 Asp Lys Leu Val Tyr Asn Val Leu Tyr Tyr Arg Asn Gly Lys Ala Phe 130 135 140 Lys Phe Phe His Trp Asn Ser Asn Leu Thr Ile Leu Lys Thr Asn Ile 145 150 155 160 Ser His Asn Gly Thr Tyr His Cys Ser Gly Met Gly Lys His Arg Tyr 165 170 175 Thr Ser Ala Gly Ile Ser Val Thr Val Lys Glu Leu Phe Pro Ala Pro 180 185 190 Val Leu Asn Ala Ser Val Thr Ser Pro Leu Leu Glu Gly Asn Leu Val 195 200 205 Thr Leu Ser Cys Glu Thr Lys Leu Leu Leu Gln Arg Pro Gly Leu Gln 210 215 220 Leu Tyr Phe Ser Phe Tyr Met Gly Ser Lys Thr Leu Arg Gly Arg Asn 225 230 235 240 Thr Ser Ser Glu Tyr Gln Ile Leu Thr Ala Arg Arg Glu Asp Ser Gly 245 250 255 Leu Tyr Trp Cys Glu Ala Ala Thr Glu Asp Gly Asn Val Leu Lys Arg 260 265 270 Ser Pro Glu Leu Glu Leu Gln Val Leu Gly Leu Gln Leu Pro Thr Pro 275 280 285 Val Trp Phe His 290 <210> SEQ ID NO 32 <211> LENGTH: 94 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Gas6 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(30) <400> SEQUENCE: 32 Met Ala Pro Ser Leu Ser Pro Gly Pro Ala Ala Leu Arg Arg Ala Pro 1 5 10 15 Gln Leu Leu Leu Leu Leu Leu Ala Ala Glu Cys Ala Leu Ala Ala Leu 20 25 30 Leu Pro Ala Arg Glu Ala Thr Gln Phe Leu Arg Pro Arg Gln Arg Arg 35 40 45 Ala Phe Gln Val Phe Glu Glu Ala Lys Gln Gly His Leu Glu Arg Glu 50 55 60 Cys Val Glu Glu Leu Cys Ser Arg Glu Glu Ala Arg Glu Val Phe Glu 65 70 75 80 Asn Asp Pro Glu Thr Asp Tyr Phe Tyr Pro Arg Tyr Leu Asp 85 90 <210> SEQ ID NO 33 <211> LENGTH: 87 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Protein S binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(24) <400> SEQUENCE: 33 Met Arg Val Leu Gly Gly Arg Cys Gly Ala Leu Leu Ala Cys Leu Leu 1 5 10 15 Leu Val Leu Pro Val Ser Glu Ala Asn Phe Leu Ser Lys Gln Gln Ala 20 25 30 Ser Gln Val Leu Val Arg Lys Arg Arg Ala Asn Ser Leu Leu Glu Glu 35 40 45 Thr Lys Gln Gly Asn Leu Glu Arg Glu Cys Ile Glu Glu Leu Cys Asn 50 55 60 Lys Glu Glu Ala Arg Glu Val Phe Glu Asn Asp Pro Glu Thr Asp Tyr 65 70 75 80 Phe Tyr Pro Lys Tyr Leu Val 85 <210> SEQ ID NO 34 <211> LENGTH: 202 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim3 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(21) <400> SEQUENCE: 34 Met Phe Ser His Leu Pro Phe Asp Cys Val Leu Leu Leu Leu Leu Leu 1 5 10 15 Leu Leu Thr Arg Ser Ser Glu Val Glu Tyr Arg Ala Glu Val Gly Gln 20 25 30 Asn Ala Tyr Leu Pro Cys Phe Tyr Thr Pro Ala Ala Pro Gly Asn Leu 35 40 45 Val Pro Val Cys Trp Gly Lys Gly Ala Cys Pro Val Phe Glu Cys Gly 50 55 60 Asn Val Val Leu Arg Thr Asp Glu Arg Asp Val Asn Tyr Trp Thr Ser 65 70 75 80 Arg Tyr Trp Leu Asn Gly Asp Phe Arg Lys Gly Asp Val Ser Leu Thr 85 90 95 Ile Glu Asn Val Thr Leu Ala Asp Ser Gly Ile Tyr Cys Cys Arg Ile 100 105 110 Gln Ile Pro Gly Ile Met Asn Asp Glu Lys Phe Asn Leu Lys Leu Val 115 120 125 Ile Lys Pro Ala Lys Val Thr Pro Ala Pro Thr Arg Gln Arg Asp Phe 130 135 140 Thr Ala Ala Phe Pro Arg Met Leu Thr Thr Arg Gly His Gly Pro Ala 145 150 155 160 Glu Thr Gln Thr Leu Gly Ser Leu Pro Asp Ile Asn Leu Thr Gln Ile 165 170 175 Ser Thr Leu Ala Asn Glu Leu Arg Asp Ser Arg Leu Ala Asn Asp Leu 180 185 190 Arg Asp Ser Gly Ala Thr Ile Arg Ile Gly 195 200 <210> SEQ ID NO 35 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 transmembrane domain <400> SEQUENCE: 35 Ile Tyr Ala Gly Val Cys Ile Ser Val Leu Val Leu Leu Ala Leu Leu 1 5 10 15 Gly Val Ile Ile Ala 20 <210> SEQ ID NO 36 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 transmembrane domain <400> SEQUENCE: 36 Leu Leu Met Ile Ile Ala Pro Ser Leu Gly Phe Val Leu Phe Ala Leu 1 5 10 15 Phe Val Ala Phe Leu 20 <210> SEQ ID NO 37 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI transmembrane domain <400> SEQUENCE: 37 Val Leu Phe Tyr Leu Ala Val Gly Ile Met Phe Leu Val Asn Thr Val 1 5 10 15 Leu Trp Val Thr Ile 20 <210> SEQ ID NO 38 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD8a transmembrane domain <400> SEQUENCE: 38 Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 1 5 10 15 Ser Leu Val Ile Thr 20 <210> SEQ ID NO 39 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK transmembrane domain <400> SEQUENCE: 39 Phe Gly Cys Phe Cys Gly Phe Ile Leu Ile Gly Leu Ile Leu Tyr Ile 1 5 10 15 Ser Leu Ala Ile Arg 20 <210> SEQ ID NO 40 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl transmembrane domain <400> SEQUENCE: 40 Tyr Val Leu Leu Gly Ala Val Val Ala Ala Ala Cys Val Leu Ile Leu 1 5 10 15 Ala Leu Phe Leu Val 20 <210> SEQ ID NO 41 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 transmembrane domain <400> SEQUENCE: 41 Val Pro Val Val Leu Gly Val Leu Thr Ala Leu Val Thr Ala Ala Ala 1 5 10 15 Leu Ala Leu Ile Leu 20 <210> SEQ ID NO 42 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD4 transmembrane domain <400> SEQUENCE: 42 Met Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile 1 5 10 15 Gly Leu Gly Ile Phe Phe 20 <210> SEQ ID NO 43 <211> LENGTH: 476 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 43 Ala Leu Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser 1 5 10 15 Glu Glu Asp Ser Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe 20 25 30 Cys Arg Arg Ala Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu 35 40 45 Glu Leu Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu 50 55 60 Val Leu Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu 65 70 75 80 Gly Asn Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys 85 90 95 Thr Met Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu 100 105 110 Ser Glu Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg 115 120 125 Leu Leu Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro 130 135 140 Met Val Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu 145 150 155 160 Leu Tyr Ser Arg Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr 165 170 175 Leu Leu Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser 180 185 190 Asn Arg Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu 195 200 205 Arg Asp Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys 210 215 220 Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro 225 230 235 240 Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser 245 250 255 Lys Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr 260 265 270 Arg Gly Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp 275 280 285 Tyr Leu Leu His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp 290 295 300 Glu Leu Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp 305 310 315 320 Arg Pro Thr Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu 325 330 335 Ser Leu Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr 340 345 350 Gln Leu Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr 355 360 365 Gly Leu Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr 370 375 380 Pro Gly Ala Ala Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn 385 390 395 400 Leu Arg Glu Glu Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu 405 410 415 Asp Val Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly 420 425 430 Val Leu Pro Glu Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His 435 440 445 His Ser Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe 450 455 460 Val Asp Asp Ser Leu Glu Asp Ser Glu Val Leu Met 465 470 475 <210> SEQ ID NO 44 <211> LENGTH: 422 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl signaling domain <400> SEQUENCE: 44 His Arg Arg Lys Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr 1 5 10 15 Val Glu Arg Gly Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr 20 25 30 Ser Arg Arg Thr Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu 35 40 45 Glu Leu Lys Glu Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val 50 55 60 Ala Leu Gly Lys Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu 65 70 75 80 Gly Gln Leu Asn Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr 85 90 95 Met Lys Ile Ala Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser 100 105 110 Glu Ala Val Cys Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu 115 120 125 Ile Gly Val Cys Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro 130 135 140 Val Val Ile Leu Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu 145 150 155 160 Leu Tyr Ser Arg Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met 165 170 175 Leu Val Lys Phe Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser 180 185 190 Thr Lys Arg Phe Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu 195 200 205 Asn Glu Asn Met Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys 210 215 220 Ile Tyr Asn Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro 225 230 235 240 Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser 245 250 255 Lys Ser Asp Val Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr 260 265 270 Arg Gly Gln Thr Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp 275 280 285 Tyr Leu Arg Gln Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp 290 295 300 Gly Leu Tyr Ala Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp 305 310 315 320 Arg Pro Ser Phe Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys 325 330 335 Ala Leu Pro Pro Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met 340 345 350 Asp Glu Gly Gly Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala 355 360 365 Asp Pro Pro Thr Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr 370 375 380 Ala Ala Glu Val His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr 385 390 395 400 Thr Pro Ser Pro Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro 405 410 415 Gly Gln Glu Asp Gly Ala 420 <210> SEQ ID NO 45 <211> LENGTH: 440 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 signaling domain <400> SEQUENCE: 45 Leu Arg Lys Arg Arg Lys Glu Thr Arg Phe Gly Gln Ala Phe Asp Ser 1 5 10 15 Val Met Ala Arg Gly Glu Pro Ala Val His Phe Arg Ala Ala Arg Ser 20 25 30 Phe Asn Arg Glu Arg Pro Glu Arg Ile Glu Ala Thr Leu Asp Ser Leu 35 40 45 Gly Ile Ser Asp Glu Leu Lys Glu Lys Leu Glu Asp Val Leu Ile Pro 50 55 60 Glu Gln Gln Phe Thr Leu Gly Arg Met Leu Gly Lys Gly Glu Phe Gly 65 70 75 80 Ser Val Arg Glu Ala Gln Leu Lys Gln Glu Asp Gly Ser Phe Val Lys 85 90 95 Val Ala Val Lys Met Leu Lys Ala Asp Ile Ile Ala Ser Ser Asp Ile 100 105 110 Glu Glu Phe Leu Arg Glu Ala Ala Cys Met Lys Glu Phe Asp His Pro 115 120 125 His Val Ala Lys Leu Val Gly Val Ser Leu Arg Ser Arg Ala Lys Gly 130 135 140 Arg Leu Pro Ile Pro Met Val Ile Leu Pro Phe Met Lys His Gly Asp 145 150 155 160 Leu His Ala Phe Leu Leu Ala Ser Arg Ile Gly Glu Asn Pro Phe Asn 165 170 175 Leu Pro Leu Gln Thr Leu Ile Arg Phe Met Val Asp Ile Ala Cys Gly 180 185 190 Met Glu Tyr Leu Ser Ser Arg Asn Phe Ile His Arg Asp Leu Ala Ala 195 200 205 Arg Asn Cys Met Leu Ala Glu Asp Met Thr Val Cys Val Ala Asp Phe 210 215 220 Gly Leu Ser Arg Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Cys 225 230 235 240 Ala Ser Lys Leu Pro Val Lys Trp Leu Ala Leu Glu Ser Leu Ala Asp 245 250 255 Asn Leu Tyr Thr Val Gln Ser Asp Val Trp Ala Phe Gly Val Thr Met 260 265 270 Trp Glu Ile Met Thr Arg Gly Gln Thr Pro Tyr Ala Gly Ile Glu Asn 275 280 285 Ala Glu Ile Tyr Asn Tyr Leu Ile Gly Gly Asn Arg Leu Lys Gln Pro 290 295 300 Pro Glu Cys Met Glu Asp Val Tyr Asp Leu Met Tyr Gln Cys Trp Ser 305 310 315 320 Ala Asp Pro Lys Gln Arg Pro Ser Phe Thr Cys Leu Arg Met Glu Leu 325 330 335 Glu Asn Ile Leu Gly Gln Leu Ser Val Leu Ser Ala Ser Gln Asp Pro 340 345 350 Leu Tyr Ile Asn Ile Glu Arg Ala Glu Glu Pro Thr Ala Gly Gly Ser 355 360 365 Leu Glu Leu Pro Gly Arg Asp Gln Pro Tyr Ser Gly Ala Gly Asp Gly 370 375 380 Ser Gly Met Gly Ala Val Gly Gly Thr Pro Ser Asp Cys Arg Tyr Ile 385 390 395 400 Leu Thr Pro Gly Gly Leu Ala Glu Gln Pro Gly Gln Ala Glu His Gln 405 410 415 Pro Glu Ser Pro Leu Asn Glu Thr Gln Arg Leu Leu Leu Leu Gln Gln 420 425 430 Gly Leu Leu Pro His Ser Ser Cys 435 440 <210> SEQ ID NO 46 <211> LENGTH: 261 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Syk signaling domain <400> SEQUENCE: 46 Thr Leu Glu Asp Lys Glu Leu Gly Ser Gly Asn Phe Gly Thr Val Lys 1 5 10 15 Lys Gly Tyr Tyr Gln Met Lys Lys Val Val Lys Thr Val Ala Val Lys 20 25 30 Ile Leu Lys Asn Glu Ala Asn Asp Pro Ala Leu Lys Asp Glu Leu Leu 35 40 45 Ala Glu Ala Asn Val Met Gln Gln Leu Asp Asn Pro Tyr Ile Val Arg 50 55 60 Met Ile Gly Ile Cys Glu Ala Glu Ser Trp Met Leu Val Met Glu Met 65 70 75 80 Ala Glu Leu Gly Pro Leu Asn Lys Tyr Leu Gln Gln Asn Arg His Val 85 90 95 Lys Asp Lys Asn Ile Ile Glu Leu Val His Gln Val Ser Met Gly Met 100 105 110 Lys Tyr Leu Glu Glu Ser Asn Phe Val His Arg Asp Leu Ala Ala Arg 115 120 125 Asn Val Leu Leu Val Thr Gln His Tyr Ala Lys Ile Ser Asp Phe Gly 130 135 140 Leu Ser Lys Ala Leu Arg Ala Asp Glu Asn Tyr Tyr Lys Ala Gln Thr 145 150 155 160 His Gly Lys Trp Pro Val Lys Trp Tyr Ala Pro Glu Cys Ile Asn Tyr 165 170 175 Tyr Lys Phe Ser Ser Lys Ser Asp Val Trp Ser Phe Gly Val Leu Met 180 185 190 Trp Glu Ala Phe Ser Tyr Gly Gln Lys Pro Tyr Arg Gly Met Lys Gly 195 200 205 Ser Glu Val Thr Ala Met Leu Glu Lys Gly Glu Arg Met Gly Cys Pro 210 215 220 Ala Gly Cys Pro Arg Glu Met Tyr Asp Leu Met Asn Leu Cys Trp Thr 225 230 235 240 Tyr Asp Val Glu Asn Arg Pro Gly Phe Ala Ala Val Glu Leu Arg Leu 245 250 255 Arg Asn Tyr Tyr Tyr 260 <210> SEQ ID NO 47 <211> LENGTH: 263 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Zap70 signaling domain <400> SEQUENCE: 47 Leu Ile Ala Asp Ile Glu Leu Gly Cys Gly Asn Phe Gly Ser Val Arg 1 5 10 15 Gln Gly Val Tyr Arg Met Arg Lys Lys Gln Ile Asp Val Ala Ile Lys 20 25 30 Val Leu Lys Gln Gly Thr Glu Lys Ala Asp Thr Glu Glu Met Met Arg 35 40 45 Glu Ala Gln Ile Met His Gln Leu Asp Asn Pro Tyr Ile Val Arg Leu 50 55 60 Ile Gly Val Cys Gln Ala Glu Ala Leu Met Leu Val Met Glu Met Ala 65 70 75 80 Gly Gly Gly Pro Leu His Lys Phe Leu Val Gly Lys Arg Glu Glu Ile 85 90 95 Pro Val Ser Asn Val Ala Glu Leu Leu His Gln Val Ser Met Gly Met 100 105 110 Lys Tyr Leu Glu Glu Lys Asn Phe Val His Arg Asp Leu Ala Ala Arg 115 120 125 Asn Val Leu Leu Val Asn Arg His Tyr Ala Lys Ile Ser Asp Phe Gly 130 135 140 Leu Ser Lys Ala Leu Gly Ala Asp Asp Ser Tyr Tyr Thr Ala Arg Ser 145 150 155 160 Ala Gly Lys Trp Pro Leu Lys Trp Tyr Ala Pro Glu Cys Ile Asn Phe 165 170 175 Arg Lys Phe Ser Ser Arg Ser Asp Val Trp Ser Tyr Gly Val Thr Met 180 185 190 Trp Glu Ala Leu Ser Tyr Gly Gln Lys Pro Tyr Lys Lys Met Lys Gly 195 200 205 Pro Glu Val Met Ala Phe Ile Glu Gln Gly Lys Arg Met Glu Cys Pro 210 215 220 Pro Glu Cys Pro Pro Glu Leu Tyr Ala Leu Met Ser Asp Cys Trp Ile 225 230 235 240 Tyr Lys Trp Glu Asp Arg Pro Asp Phe Leu Thr Val Glu Gln Arg Met 245 250 255 Arg Ala Cys Tyr Tyr Ser Leu 260 <210> SEQ ID NO 48 <211> LENGTH: 61 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI signaling domain <400> SEQUENCE: 48 Arg Lys Glu Leu Lys Arg Lys Lys Lys Trp Asp Leu Glu Ile Ser Leu 1 5 10 15 Asp Ser Gly His Glu Lys Lys Val Ile Ser Ser Leu Gln Glu Asp Arg 20 25 30 His Leu Glu Glu Glu Leu Lys Cys Gln Glu Gln Lys Glu Glu Gln Leu 35 40 45 Gln Glu Gly Val His Arg Lys Glu Pro Gln Gly Ala Thr 50 55 60 <210> SEQ ID NO 49 <211> LENGTH: 77 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2A signaling domain <400> SEQUENCE: 49 Cys Arg Lys Lys Arg Ile Ser Ala Asn Ser Thr Asp Pro Val Lys Ala 1 5 10 15 Ala Gln Phe Glu Pro Pro Gly Arg Gln Met Ile Ala Ile Arg Lys Arg 20 25 30 Gln Leu Glu Glu Thr Asn Asn Asp Tyr Glu Thr Ala Asp Gly Gly Tyr 35 40 45 Met Thr Leu Asn Pro Arg Ala Pro Thr Asp Asp Asp Lys Asn Ile Tyr 50 55 60 Leu Thr Leu Pro Pro Asn Asp His Val Asn Ser Asn Asn 65 70 75 <210> SEQ ID NO 50 <211> LENGTH: 77 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2C signaling domain <400> SEQUENCE: 50 Cys Arg Lys Lys Arg Ile Ser Ala Asn Ser Thr Asp Pro Val Lys Ala 1 5 10 15 Ala Gln Phe Glu Pro Pro Gly Arg Gln Met Ile Ala Ile Arg Lys Arg 20 25 30 Gln Pro Glu Glu Thr Asn Asn Asp Tyr Glu Thr Ala Asp Gly Gly Tyr 35 40 45 Met Thr Leu Asn Pro Arg Ala Pro Thr Asp Asp Asp Lys Asn Ile Tyr 50 55 60 Leu Thr Leu Pro Pro Asn Asp His Val Asn Ser Asn Asn 65 70 75 <210> SEQ ID NO 51 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR3A signaling domain <400> SEQUENCE: 51 Lys Thr Asn Ile Arg Ser Ser Thr Arg Asp Trp Lys Asp His Lys Phe 1 5 10 15 Lys Trp Arg Lys Asp Pro Gln Asp Lys 20 25 <210> SEQ ID NO 52 <211> LENGTH: 56 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 52 Lys Leu Leu Val Thr Ile His Asp Arg Arg Glu Phe Ala Lys Phe Gln 1 5 10 15 Ser Glu Arg Ser Arg Ala Arg Tyr Glu Met Ala Ser Asn Pro Leu Tyr 20 25 30 Arg Lys Pro Ile Ser Thr His Thr Val Asp Phe Ala Phe Asn Lys Phe 35 40 45 Asn Lys Ser Tyr Asn Gly Ser Val 50 55 <210> SEQ ID NO 53 <211> LENGTH: 296 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MyD88 signaling domain <400> SEQUENCE: 53 Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser 1 5 10 15 Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg 20 25 30 Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr 35 40 45 Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu 50 55 60 Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly 65 70 75 80 Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu 85 90 95 Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp 100 105 110 Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro 115 120 125 Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu 130 135 140 Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly His Met Pro Glu Arg 145 150 155 160 Phe Asp Ala Phe Ile Cys Tyr Cys Pro Ser Asp Ile Gln Phe Val Gln 165 170 175 Glu Met Ile Arg Gln Leu Glu Gln Thr Asn Tyr Arg Leu Lys Leu Cys 180 185 190 Val Ser Asp Arg Asp Val Leu Pro Gly Thr Cys Val Trp Ser Ile Ala 195 200 205 Ser Glu Leu Ile Glu Lys Arg Cys Arg Arg Met Val Val Val Val Ser 210 215 220 Asp Asp Tyr Leu Gln Ser Lys Glu Cys Asp Phe Gln Thr Lys Phe Ala 225 230 235 240 Leu Ser Leu Ser Pro Gly Ala His Gln Lys Arg Leu Ile Pro Ile Lys 245 250 255 Tyr Lys Ala Met Lys Lys Glu Phe Pro Ser Ile Leu Arg Phe Ile Thr 260 265 270 Val Cys Asp Tyr Thr Asn Pro Cys Thr Lys Ser Trp Phe Trp Thr Arg 275 280 285 Leu Ala Lys Ala Leu Ser Leu Pro 290 295 <210> SEQ ID NO 54 <211> LENGTH: 522 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Traf6 signaling domain <400> SEQUENCE: 54 Met Ser Leu Leu Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu 1 5 10 15 Ser Asp Cys Cys Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys 20 25 30 Asp Asp Ser Val Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser 35 40 45 Phe Met Glu Glu Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu 50 55 60 Glu Ser Lys Tyr Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala 65 70 75 80 Val Gln Thr Pro Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys 85 90 95 Ser Ile Arg Asp Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu 100 105 110 Leu Glu Asn Gln Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu 115 120 125 Ser Leu Met Val Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu 130 135 140 Leu Arg His Leu Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met 145 150 155 160 Asp Cys Pro Gln Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile 165 170 175 His Ile Leu Lys Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys 180 185 190 Ala Ala Ser Met Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys 195 200 205 Pro Leu Ala Asn Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg 210 215 220 Glu Gln Met Pro Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile 225 230 235 240 Pro Cys Thr Phe Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn 245 250 255 His Leu Ala Arg His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met 260 265 270 Leu Ala Gln Ala Val His Ser Leu Ser Val Ile Pro Asp Ser Gly Tyr 275 280 285 Ile Ser Glu Val Arg Asn Phe Gln Glu Thr Ile His Gln Leu Glu Gly 290 295 300 Arg Leu Val Arg Gln Asp His Gln Ile Arg Glu Leu Thr Ala Lys Met 305 310 315 320 Glu Thr Gln Ser Met Tyr Val Ser Glu Leu Lys Arg Thr Ile Arg Thr 325 330 335 Leu Glu Asp Lys Val Ala Glu Ile Glu Ala Gln Gln Cys Asn Gly Ile 340 345 350 Tyr Ile Trp Lys Ile Gly Asn Phe Gly Met His Leu Lys Cys Gln Glu 355 360 365 Glu Glu Lys Pro Val Val Ile His Ser Pro Gly Phe Tyr Thr Gly Lys 370 375 380 Pro Gly Tyr Lys Leu Cys Met Arg Leu His Leu Gln Leu Pro Thr Ala 385 390 395 400 Gln Arg Cys Ala Asn Tyr Ile Ser Leu Phe Val His Thr Met Gln Gly 405 410 415 Glu Tyr Asp Ser His Leu Pro Trp Pro Phe Gln Gly Thr Ile Arg Leu 420 425 430 Thr Ile Leu Asp Gln Ser Glu Ala Pro Val Arg Gln Asn His Glu Glu 435 440 445 Ile Met Asp Ala Lys Pro Glu Leu Leu Ala Phe Gln Arg Pro Thr Ile 450 455 460 Pro Arg Asn Pro Lys Gly Phe Gly Tyr Val Thr Phe Met His Leu Glu 465 470 475 480 Ala Leu Arg Gln Arg Thr Phe Ile Lys Asp Asp Thr Leu Leu Val Arg 485 490 495 Cys Glu Val Ser Thr Arg Phe Asp Met Gly Ser Leu Arg Arg Glu Gly 500 505 510 Phe Gln Pro Arg Ser Thr Asp Ala Gly Val 515 520 <210> SEQ ID NO 55 <211> LENGTH: 138 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 signaling domain <400> SEQUENCE: 55 tataagaaac ggcgcgttca tcttcctcag gagggggcat ttgaaaatac gttgtacttc 60 aacagccaga gcagtccagg tacgtctgat atgaaggatt tggtggggaa cattgaacag 120 aacgagcata gcgttata 138 <210> SEQ ID NO 56 <211> LENGTH: 46 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 signaling domain <400> SEQUENCE: 56 Tyr Lys Lys Arg Arg Val His Leu Pro Gln Glu Gly Ala Phe Glu Asn 1 5 10 15 Thr Leu Tyr Phe Asn Ser Gln Ser Ser Pro Gly Thr Ser Asp Met Lys 20 25 30 Asp Leu Val Gly Asn Ile Glu Gln Asn Glu His Ser Val Ile 35 40 45 <210> SEQ ID NO 57 <211> LENGTH: 1080 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: TIM4 extracellular and transmembrane domains <400> SEQUENCE: 57 ttctctaggc gccggaattc gccaccatgt ctaaaggtct tcttctgctg tggctggtta 60 ctgaactgtg gtggttgtat ctcactcctg cagcaagtga ggataccatc attggtttct 120 tggggcagcc cgtcaccctc ccttgtcact accttagctg gagccagagc agaaatagta 180 tgtgttgggg taagggctcc tgtcctaata gcaaatgtaa tgcagagctc ttgcgaacag 240 acgggacacg gatcatcagt agaaagtcta ctaagtatac cttgcttggg aaggtacaat 300 ttggggaagt gtccctcact attagtaata caaatagagg tgacagcgga gtctattgct 360 gtagaataga agtaccaggt tggtttaacg atgtcaaaaa aaatgtacgg ctcgaattga 420 ggagggctac cactaccaag aaaccaacta caaccacccg ccccactaca accccttacg 480 tcaccacaac aacccctgaa ctgctgccca caactgtgat gaccaccagt gttcttccca 540 ctaccactcc tccccagacc ctggctacta ccgctttctc aacagccgta actacttgtc 600 cctcaactac ccctgggtca ttcagtcagg aaactacaaa ggggtccgct ttcactactg 660 agtcagaaac cctccctgct tctaatcact ctcaacgcag catgatgaca atatcaactg 720 acatcgctgt tctgagacca actggaagca atcccggtat cttgccctcc acatctcagc 780 tgacaacaca aaaaactacc ctgaccacat cagaatccct tcagaagaca actaagtccc 840 accaaatcaa ttcccgacag actattctta taatagcctg ttgtgtgggg tttgtgctga 900 tggttttgtt gttcctggct tttttgcttc gcggcaaggt gactggtgcc aactgtctcc 960 aaaggcacaa aaggccagac aatacggaag attctgattc cgtgcttaac gatatgagcc 1020 acgggcggga cgatgaggat ggtatattca ccttgtgagc ggccgcccct ctccctcccc 1080 <210> SEQ ID NO 58 <211> LENGTH: 1428 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 58 gctcttagga ggagggtgca ggagacaaag tttggtgggg ctttctcaga ggaggatagc 60 cagctcgttg taaactaccg ggccaagaaa tccttttgca gaagagcaat tgaacttaca 120 ttgcaaagcc tcggagtgtc tgaggagctt cagaataaac ttgaggacgt ggtcatcgat 180 cgcaaccttc ttgtgctggg gaaggtcttg ggagagggag agttcgggtc cgtgatggaa 240 ggtaacctta aacaagagga tggaactagc caaaaagtcg ccgtaaagac tatgaagctg 300 gataatttta gtcagcggga aattgaggaa tttctttcag aggccgcttg catgaaggat 360 ttcaaccatc ccaatgttat caggctcctt ggtgtctgta tcgagcttag ttcccagggc 420 atacctaaac ctatggttat actgcctttc atgaagtatg gtgatctgca cacctttctt 480 ctctactccc ggcttaatac cgggccaaag tatatccacc tccaaaccct cttgaagttc 540 atgatggaca tagcacaggg gatggagtac ctttctaata ggaattttct tcacagggat 600 ttggccgccc gaaattgtat gctcagagat gatatgactg tttgcgtcgc agattttgga 660 cttagcaaga aaatctacag tggtgattac tacagacagg gacgcattgc aaagatgcct 720 gtgaagtgga tagccatcga atcactggcc gatagggttt atacttccaa atccgatgtt 780 tgggcctttg gtgtgactat gtgggaaata acaacacggg ggatgactcc ttatcccggt 840 gttcaaaatc atgagatgta cgattatctc ctccacgggc accgacttaa acagcccgag 900 gactgcctgg acgaactgta tgacattatg tactcttgtt ggagcgctga tccattggac 960 cggcccactt tttccgtgct gcgacttcag ctggagaagc tgagtgagtc tctgcctgac 1020 gctcaggata aagagtcaat tatatacatc aacactcagc tccttgaatc ctgtgagggg 1080 atcgcaaacg gaccttcact cactggcttg gacatgaata ttgatcccga ctccattatt 1140 gcttcctgta cacctggagc agctgtgagt gtggtaaccg ctgaggttca tgaaaataac 1200 ttgcgcgaag aaaggtatat actgaatggg ggaaacgagg aatgggaaga cgtatccagt 1260 accccatttg ctgctgtgac ccccgagaag gatggggttc tgccagaaga tagactcacc 1320 aaaaatggtg tttcctggag tcaccattcc acacttcccc ttggcagtcc aagccctgac 1380 gaactccttt ttgtagatga cagccttgag gacagcgaag tgctgatg 1428 <210> SEQ ID NO 59 <211> LENGTH: 2100 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FA58C2-IgG4-CD28-MERTK CER03 chimeric engulfment receptor <400> SEQUENCE: 59 atgttgctgc tcgttacgtc tctgctcctg tgcgaactgc cgcaccccgc cttcctcctg 60 attccgctga acggctgcgc taatccgctc ggtctgaaaa acaattctat acctgataaa 120 caaatcaccg cctcatcctc ttacaagacg tggggactcc atctcttttc ttggaaccca 180 tcttatgctc gactggacaa acaaggcaat ttcaatgcat gggtcgccgg gagttacggt 240 aacgaccaat ggctccaggt agaccttggt agtagtaagg aggtcacggg tatcatcaca 300 cagggggccc ggaatttcgg ttcagtgcag ttcgttgctt cctacaaggt cgcttattca 360 aacgatagtg ctaattggac agagtaccaa gaccctcgca cgggaagtag taagattttc 420 ccaggcaact gggataacca cagtcacaaa aaaaacttgt tcgagacgcc gatattggcg 480 agatatgtcc ggatacttcc ggtcgcgtgg cataacagaa ttgccctgag gctggaattg 540 ctgggatgcg aaagtaaata tggaccgcca tgccccccat gccccatgtt ttgggtgttg 600 gtcgtagtgg gtggagtcct cgcttgctac tcattgctcg taacggttgc ttttattata 660 ttctgggttg ctcttaggag gagggtgcag gagacaaagt ttggtggggc tttctcagag 720 gaggatagcc agctcgttgt aaactaccgg gccaagaaat ccttttgcag aagagcaatt 780 gaacttacat tgcaaagcct cggagtgtct gaggagcttc agaataaact tgaggacgtg 840 gtcatcgatc gcaaccttct tgtgctgggg aaggtcttgg gagagggaga gttcgggtcc 900 gtgatggaag gtaaccttaa acaagaggat ggaactagcc aaaaagtcgc cgtaaagact 960 atgaagctgg ataattttag tcagcgggaa attgaggaat ttctttcaga ggccgcttgc 1020 atgaaggatt tcaaccatcc caatgttatc aggctccttg gtgtctgtat cgagcttagt 1080 tcccagggca tacctaaacc tatggttata ctgcctttca tgaagtatgg tgatctgcac 1140 acctttcttc tctactcccg gcttaatacc gggccaaagt atatccacct ccaaaccctc 1200 ttgaagttca tgatggacat agcacagggg atggagtacc tttctaatag gaattttctt 1260 cacagggatt tggccgcccg aaattgtatg ctcagagatg atatgactgt ttgcgtcgca 1320 gattttggac ttagcaagaa aatctacagt ggtgattact acagacaggg acgcattgca 1380 aagatgcctg tgaagtggat agccatcgaa tcactggccg atagggttta tacttccaaa 1440 tccgatgttt gggcctttgg tgtgactatg tgggaaataa caacacgggg gatgactcct 1500 tatcccggtg ttcaaaatca tgagatgtac gattatctcc tccacgggca ccgacttaaa 1560 cagcccgagg actgcctgga cgaactgtat gacattatgt actcttgttg gagcgctgat 1620 ccattggacc ggcccacttt ttccgtgctg cgacttcagc tggagaagct gagtgagtct 1680 ctgcctgacg ctcaggataa agagtcaatt atatacatca acactcagct ccttgaatcc 1740 tgtgagggga tcgcaaacgg accttcactc actggcttgg acatgaatat tgatcccgac 1800 tccattattg cttcctgtac acctggagca gctgtgagtg tggtaaccgc tgaggttcat 1860 gaaaataact tgcgcgaaga aaggtatata ctgaatgggg gaaacgagga atgggaagac 1920 gtatccagta ccccatttgc tgctgtgacc cccgagaagg atggggttct gccagaagat 1980 agactcacca aaaatggtgt ttcctggagt caccattcca cacttcccct tggcagtcca 2040 agccctgacg aactcctttt tgtagatgac agccttgagg acagcgaagt gctgatgtga 2100 <210> SEQ ID NO 60 <211> LENGTH: 576 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rac1 <400> SEQUENCE: 60 atgcaagcca ttaagtgcgt agtagttggt gatggagccg tcggcaaaac atgcctgctg 60 atctcttata ccacaaacgc attcccgggc gagtacattc ccactgtatt tgacaactac 120 agtgctaacg tcatggtaga tggtaagccg gttaacctcg gactctggga taccgccggc 180 caggaagact atgatagact tagaccgctc agctatccgc aaaccgatgt gttcctgatt 240 tgctttagcc tggtctcccc cgcttcattt gagaatgtga gagcgaagtg gtatccagag 300 gtgcgccatc actgtccgaa cacacccatt atactcgtgg ggactaaact cgacctgagg 360 gatgacaagg acaccatcga aaaactgaaa gaaaagaaac ttacaccaat aacgtaccct 420 cagggtctgg ctatggcaaa agaaattggc gcggtgaaat acctggaatg cagtgcgctc 480 acccagcggg gcttgaagac ggtgttcgat gaggctatac gcgccgtgct gtgtccccca 540 ccagtgaaga aacgaaaacg aaagtgtctt ctcctt 576 <210> SEQ ID NO 61 <211> LENGTH: 645 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rab5 <400> SEQUENCE: 61 atggcgtctc gcggagccac tcgcccaaac ggcccaaaca ctggcaataa aatttgccaa 60 ttcaagttgg tacttctcgg ggaaagtgct gtgggtaagt catctctcgt acttcgcttc 120 gtgaaagggc agtttcacga gttccaagag tctactatcg gagcggcatt cttgacgcag 180 acagtatgtc tggacgacac tactgtaaaa tttgaaatat gggatacagc ggggcaagag 240 aggtatcact ctcttgctcc gatgtattat agaggcgcgc aagcggccat agtcgtatat 300 gatattacca atgaggaatc atttgcacgg gcgaaaaatt gggtaaaaga actgcagcgc 360 caggcgtcac ccaatatagt aattgctttg tctggaaata aggcagattt ggctaacaag 420 cgcgcggtag actttcaaga ggctcaaagc tacgcagacg acaatagttt gctgttcatg 480 gaaacatcag cgaaaactag tatgaatgta aacgaaatct tcatggcaat cgctaagaaa 540 ctcccaaaaa acgagccgca gaaccctggg gccaacagcg caaggggaag aggcgttgac 600 ttgactgagc cgactcaacc aaccagaaac caatgctgtt ccaac 645 <210> SEQ ID NO 62 <211> LENGTH: 1281 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Rac1-P2A-Rab5a construct <400> SEQUENCE: 62 atgcaagcca ttaagtgcgt agtagttggt gatggagccg tcggcaaaac atgcctgctg 60 atctcttata ccacaaacgc attcccgggc gagtacattc ccactgtatt tgacaactac 120 agtgctaacg tcatggtaga tggtaagccg gttaacctcg gactctggga taccgccggc 180 caggaagact atgatagact tagaccgctc agctatccgc aaaccgatgt gttcctgatt 240 tgctttagcc tggtctcccc cgcttcattt gagaatgtga gagcgaagtg gtatccagag 300 gtgcgccatc actgtccgaa cacacccatt atactcgtgg ggactaaact cgacctgagg 360 gatgacaagg acaccatcga aaaactgaaa gaaaagaaac ttacaccaat aacgtaccct 420 cagggtctgg ctatggcaaa agaaattggc gcggtgaaat acctggaatg cagtgcgctc 480 acccagcggg gcttgaagac ggtgttcgat gaggctatac gcgccgtgct gtgtccccca 540 ccagtgaaga aacgaaaacg aaagtgtctt ctccttgcca ccaacttcag cctgctgaag 600 caggccggcg acgtggagga gaaccccggc cccatggcgt ctcgcggagc cactcgccca 660 aacggcccaa acactggcaa taaaatttgc caattcaagt tggtacttct cggggaaagt 720 gctgtgggta agtcatctct cgtacttcgc ttcgtgaaag ggcagtttca cgagttccaa 780 gagtctacta tcggagcggc attcttgacg cagacagtat gtctggacga cactactgta 840 aaatttgaaa tatgggatac agcggggcaa gagaggtatc actctcttgc tccgatgtat 900 tatagaggcg cgcaagcggc catagtcgta tatgatatta ccaatgagga atcatttgca 960 cgggcgaaaa attgggtaaa agaactgcag cgccaggcgt cacccaatat agtaattgct 1020 ttgtctggaa ataaggcaga tttggctaac aagcgcgcgg tagactttca agaggctcaa 1080 agctacgcag acgacaatag tttgctgttc atggaaacat cagcgaaaac tagtatgaat 1140 gtaaacgaaa tcttcatggc aatcgctaag aaactcccaa aaaacgagcc gcagaaccct 1200 ggggccaaca gcgcaagggg aagaggcgtt gacttgactg agccgactca accaaccaga 1260 aaccaatgct gttccaactg a 1281 <210> SEQ ID NO 63 <211> LENGTH: 1455 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FA58C2-IgG4-CD28-Syk CER04 chimeric engulfment receptor <400> SEQUENCE: 63 atgttgctgc tcgttacgtc tctgctcctg tgcgaactgc cgcaccccgc cttcctcctg 60 attccgctga acggctgcgc taatccgctc ggtctgaaaa acaattctat acctgataaa 120 caaatcaccg cctcatcctc ttacaagacg tggggactcc atctcttttc ttggaaccca 180 tcttatgctc gactggacaa acaaggcaat ttcaatgcat gggtcgccgg gagttacggt 240 aacgaccaat ggctccaggt agaccttggt agtagtaagg aggtcacggg tatcatcaca 300 cagggggccc ggaatttcgg ttcagtgcag ttcgttgctt cctacaaggt cgcttattca 360 aacgatagtg ctaattggac agagtaccaa gaccctcgca cgggaagtag taagattttc 420 ccaggcaact gggataacca cagtcacaaa aaaaacttgt tcgagacgcc gatattggcg 480 agatatgtcc ggatacttcc ggtcgcgtgg cataacagaa ttgccctgag gctggaattg 540 ctgggatgcg aaagtaaata tggaccgcca tgccccccat gccccatgtt ttgggtgttg 600 gtcgtagtgg gtggagtcct cgcttgctac tcattgctcg taacggttgc ttttattata 660 ttctgggtta cactcgagga taaagagctc ggatctggta atttcggcac agttaagaaa 720 gggtactacc aaatgaagaa agttgttaag actgtagccg tcaagatact caaaaacgaa 780 gcgaatgatc cggcgctgaa agacgaattg ctcgcggaag cgaacgtgat gcaacagctg 840 gataatccct acattgtcag gatgatagga atatgtgagg ctgaaagctg gatgcttgtt 900 atggagatgg cggagcttgg acccctgaac aaatacctcc agcagaatcg gcatgtgaag 960 gataagaata tcatagaatt ggtccaccag gtttcaatgg gtatgaagta tctggaagaa 1020 agtaacttcg ttcatcggga cttggccgcg cgcaatgtct tgcttgtcac gcaacactac 1080 gccaaaatat ccgacttcgg attgagtaag gccctgcgag cagacgaaaa ttattataag 1140 gctcagacac atggaaaatg gcctgtaaag tggtacgcgc ctgagtgcat caactactac 1200 aagttttcaa gtaaatctga tgtatggagc tttggtgtgc tgatgtggga agctttttct 1260 tatggccaaa aaccgtatag aggaatgaag ggatcagaag tcaccgcaat gctcgaaaaa 1320 ggtgaaagga tggggtgccc cgcgggatgc cctcgagaga tgtatgacct gatgaacctt 1380 tgctggactt atgatgtaga gaatagacct gggttcgcag ccgttgagtt gcgcctcagg 1440 aattactact attga 1455 <210> SEQ ID NO 64 <211> LENGTH: 783 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GMCSF-FMC63-IgG4-CD28-MERTK CER40 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: GM-CSF signal peptide <400> SEQUENCE: 64 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser -5 1 5 10 Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser 15 20 25 Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly 30 35 40 Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 45 50 55 Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr 60 65 70 Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln 75 80 85 90 Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 95 100 105 Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 110 115 120 Thr Lys Gly Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 125 130 135 Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu 140 145 150 Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 155 160 165 170 Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 175 180 185 Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln 190 195 200 Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr 205 210 215 Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 220 225 230 Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Ser Lys Tyr Gly 235 240 245 250 Pro Pro Cys Pro Pro Cys Pro Met Phe Trp Val Leu Val Val Val Gly 255 260 265 Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile 270 275 280 Phe Trp Val Ala Leu Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly 285 290 295 Ala Phe Ser Glu Glu Asp Ser Gln Leu Val Val Asn Tyr Arg Ala Lys 300 305 310 Lys Ser Phe Cys Arg Arg Ala Ile Glu Leu Thr Leu Gln Ser Leu Gly 315 320 325 330 Val Ser Glu Glu Leu Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg 335 340 345 Asn Leu Leu Val Leu Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser 350 355 360 Val Met Glu Gly Asn Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val 365 370 375 Ala Val Lys Thr Met Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu 380 385 390 Glu Phe Leu Ser Glu Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn 395 400 405 410 Val Ile Arg Leu Leu Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile 415 420 425 Pro Lys Pro Met Val Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His 430 435 440 Thr Phe Leu Leu Tyr Ser Arg Leu Asn Thr Gly Pro Lys Tyr Ile His 445 450 455 Leu Gln Thr Leu Leu Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu 460 465 470 Tyr Leu Ser Asn Arg Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn 475 480 485 490 Cys Met Leu Arg Asp Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu 495 500 505 Ser Lys Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala 510 515 520 Lys Met Pro Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val 525 530 535 Tyr Thr Ser Lys Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu 540 545 550 Ile Thr Thr Arg Gly Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu 555 560 565 570 Met Tyr Asp Tyr Leu Leu His Gly His Arg Leu Lys Gln Pro Glu Asp 575 580 585 Cys Leu Asp Glu Leu Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp 590 595 600 Pro Leu Asp Arg Pro Thr Phe Ser Val Leu Arg Leu Gln Leu Glu Lys 605 610 615 Leu Ser Glu Ser Leu Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr 620 625 630 Ile Asn Thr Gln Leu Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro 635 640 645 650 Ser Leu Thr Gly Leu Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala 655 660 665 Ser Cys Thr Pro Gly Ala Ala Val Ser Val Val Thr Ala Glu Val His 670 675 680 Glu Asn Asn Leu Arg Glu Glu Arg Tyr Ile Leu Asn Gly Gly Asn Glu 685 690 695 Glu Trp Glu Asp Val Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu 700 705 710 Lys Asp Gly Val Leu Pro Glu Asp Arg Leu Thr Lys Asn Gly Val Ser 715 720 725 730 Trp Ser His His Ser Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu 735 740 745 Leu Leu Phe Val Asp Asp Ser Leu Glu Asp Ser Glu Val Leu Met 750 755 760 <210> SEQ ID NO 65 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: GM-CSF signal peptide <400> SEQUENCE: 65 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 1 5 10 15 Ala Phe Leu Leu Ile Pro 20 <210> SEQ ID NO 66 <211> LENGTH: 245 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: anti-CD19 FMC63 scFv <400> SEQUENCE: 66 Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly 100 105 110 Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys 115 120 125 Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser 130 135 140 Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 145 150 155 160 Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile 165 170 175 Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu 180 185 190 Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn 195 200 205 Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 210 215 220 Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 225 230 235 240 Val Thr Val Ser Ser 245 <210> SEQ ID NO 67 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: modified IgG4 hinge region <400> SEQUENCE: 67 Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 1 5 10 <210> SEQ ID NO 68 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD28 transmembrane domain <400> SEQUENCE: 68 Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 1 5 10 15 Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 20 25 <210> SEQ ID NO 69 <211> LENGTH: 473 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 69 Lys Arg Val Gln Glu Thr Lys Phe Gly Asn Ala Phe Thr Glu Glu Asp 1 5 10 15 Ser Glu Leu Val Val Asn Tyr Ile Ala Lys Lys Ser Phe Cys Arg Arg 20 25 30 Ala Ile Glu Leu Thr Leu His Ser Leu Gly Val Ser Glu Glu Leu Gln 35 40 45 Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Ile Leu Gly 50 55 60 Lys Ile Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu 65 70 75 80 Lys Gln Glu Asp Gly Thr Ser Leu Lys Val Ala Val Lys Thr Met Lys 85 90 95 Leu Asp Asn Ser Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala 100 105 110 Ala Cys Met Lys Asp Phe Ser His Pro Asn Val Ile Arg Leu Leu Gly 115 120 125 Val Cys Ile Glu Met Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile 130 135 140 Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Tyr Leu Leu Tyr Ser 145 150 155 160 Arg Leu Glu Thr Gly Pro Lys His Ile Pro Leu Gln Thr Leu Leu Lys 165 170 175 Phe Met Val Asp Ile Ala Leu Gly Met Glu Tyr Leu Ser Asn Arg Asn 180 185 190 Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp 195 200 205 Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser 210 215 220 Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp 225 230 235 240 Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp 245 250 255 Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Met 260 265 270 Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu 275 280 285 His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr 290 295 300 Glu Ile Met Tyr Ser Cys Trp Arg Thr Asp Pro Leu Asp Arg Pro Thr 305 310 315 320 Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Leu Glu Ser Leu Pro 325 330 335 Asp Val Arg Asn Gln Ala Asp Val Ile Tyr Val Asn Thr Gln Leu Leu 340 345 350 Glu Ser Ser Glu Gly Leu Ala Gln Gly Ser Thr Leu Ala Pro Leu Asp 355 360 365 Leu Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Arg Ala 370 375 380 Ala Ile Ser Val Val Thr Ala Glu Val His Asp Ser Lys Pro His Glu 385 390 395 400 Gly Arg Tyr Ile Leu Asn Gly Gly Ser Glu Glu Trp Glu Asp Leu Thr 405 410 415 Ser Ala Pro Ser Ala Ala Val Thr Ala Glu Lys Asn Ser Val Leu Pro 420 425 430 Gly Glu Arg Leu Val Arg Asn Gly Val Ser Trp Ser His Ser Ser Met 435 440 445 Leu Pro Leu Gly Ser Ser Leu Pro Asp Glu Leu Leu Phe Ala Asp Asp 450 455 460 Ser Ser Glu Gly Ser Glu Val Leu Met 465 470 <210> SEQ ID NO 70 <211> LENGTH: 484 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GMCSF-FA58C2-IgG4-CD28-SYK CER04 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: GM-CSF signal peptide <400> SEQUENCE: 70 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Leu Asn Gly Cys Ala Asn Pro Leu Gly Leu -5 1 5 10 Lys Asn Asn Ser Ile Pro Asp Lys Gln Ile Thr Ala Ser Ser Ser Tyr 15 20 25 Lys Thr Trp Gly Leu His Leu Phe Ser Trp Asn Pro Ser Tyr Ala Arg 30 35 40 Leu Asp Lys Gln Gly Asn Phe Asn Ala Trp Val Ala Gly Ser Tyr Gly 45 50 55 Asn Asp Gln Trp Leu Gln Val Asp Leu Gly Ser Ser Lys Glu Val Thr 60 65 70 Gly Ile Ile Thr Gln Gly Ala Arg Asn Phe Gly Ser Val Gln Phe Val 75 80 85 90 Ala Ser Tyr Lys Val Ala Tyr Ser Asn Asp Ser Ala Asn Trp Thr Glu 95 100 105 Tyr Gln Asp Pro Arg Thr Gly Ser Ser Lys Ile Phe Pro Gly Asn Trp 110 115 120 Asp Asn His Ser His Lys Lys Asn Leu Phe Glu Thr Pro Ile Leu Ala 125 130 135 Arg Tyr Val Arg Ile Leu Pro Val Ala Trp His Asn Arg Ile Ala Leu 140 145 150 Arg Leu Glu Leu Leu Gly Cys Glu Ser Lys Tyr Gly Pro Pro Cys Pro 155 160 165 170 Pro Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala 175 180 185 Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Thr 190 195 200 Leu Glu Asp Lys Glu Leu Gly Ser Gly Asn Phe Gly Thr Val Lys Lys 205 210 215 Gly Tyr Tyr Gln Met Lys Lys Val Val Lys Thr Val Ala Val Lys Ile 220 225 230 Leu Lys Asn Glu Ala Asn Asp Pro Ala Leu Lys Asp Glu Leu Leu Ala 235 240 245 250 Glu Ala Asn Val Met Gln Gln Leu Asp Asn Pro Tyr Ile Val Arg Met 255 260 265 Ile Gly Ile Cys Glu Ala Glu Ser Trp Met Leu Val Met Glu Met Ala 270 275 280 Glu Leu Gly Pro Leu Asn Lys Tyr Leu Gln Gln Asn Arg His Val Lys 285 290 295 Asp Lys Asn Ile Ile Glu Leu Val His Gln Val Ser Met Gly Met Lys 300 305 310 Tyr Leu Glu Glu Ser Asn Phe Val His Arg Asp Leu Ala Ala Arg Asn 315 320 325 330 Val Leu Leu Val Thr Gln His Tyr Ala Lys Ile Ser Asp Phe Gly Leu 335 340 345 Ser Lys Ala Leu Arg Ala Asp Glu Asn Tyr Tyr Lys Ala Gln Thr His 350 355 360 Gly Lys Trp Pro Val Lys Trp Tyr Ala Pro Glu Cys Ile Asn Tyr Tyr 365 370 375 Lys Phe Ser Ser Lys Ser Asp Val Trp Ser Phe Gly Val Leu Met Trp 380 385 390 Glu Ala Phe Ser Tyr Gly Gln Lys Pro Tyr Arg Gly Met Lys Gly Ser 395 400 405 410 Glu Val Thr Ala Met Leu Glu Lys Gly Glu Arg Met Gly Cys Pro Ala 415 420 425 Gly Cys Pro Arg Glu Met Tyr Asp Leu Met Asn Leu Cys Trp Thr Tyr 430 435 440 Asp Val Glu Asn Arg Pro Gly Phe Ala Ala Val Glu Leu Arg Leu Arg 445 450 455 Asn Tyr Tyr Tyr 460 <210> SEQ ID NO 71 <211> LENGTH: 776 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4-MERTK CER01 mouse chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 71 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met 750 <210> SEQ ID NO 72 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 72 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp 1 5 10 15 Leu Tyr Leu Thr Pro Ala 20 <210> SEQ ID NO 73 <211> LENGTH: 257 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain without signal peptide <400> SEQUENCE: 73 Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu Gly Gln Pro Val Thr Leu 1 5 10 15 Pro Cys His Tyr Leu Ser Trp Ser Gln Ser Arg Asn Ser Met Cys Trp 20 25 30 Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys Asn Ala Glu Leu Leu Arg 35 40 45 Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys Ser Thr Lys Tyr Thr Leu 50 55 60 Leu Gly Lys Val Gln Phe Gly Glu Val Ser Leu Thr Ile Ser Asn Thr 65 70 75 80 Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys Arg Ile Glu Val Pro Gly 85 90 95 Trp Phe Asn Asp Val Lys Lys Asn Val Arg Leu Glu Leu Arg Arg Ala 100 105 110 Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr Arg Pro Thr Thr Thr Pro 115 120 125 Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu Pro Thr Thr Val Met Thr 130 135 140 Thr Ser Val Leu Pro Thr Thr Thr Pro Pro Gln Thr Leu Ala Thr Thr 145 150 155 160 Ala Phe Ser Thr Ala Val Thr Thr Cys Pro Ser Thr Thr Pro Gly Ser 165 170 175 Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala Phe Thr Thr Glu Ser Glu 180 185 190 Thr Leu Pro Ala Ser Asn His Ser Gln Arg Ser Met Met Thr Ile Ser 195 200 205 Thr Asp Ile Ala Val Leu Arg Pro Thr Gly Ser Asn Pro Gly Ile Leu 210 215 220 Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys Thr Thr Leu Thr Thr Ser 225 230 235 240 Glu Ser Leu Gln Lys Thr Thr Lys Ser His Gln Ile Asn Ser Arg Gln 245 250 255 Thr <210> SEQ ID NO 74 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 transmembrane domain <400> SEQUENCE: 74 Ile Leu Ile Ile Ala Cys Cys Val Gly Phe Val Leu Met Val Leu Leu 1 5 10 15 Phe Leu Ala Phe Leu 20 <210> SEQ ID NO 75 <211> LENGTH: 699 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GMCSF-FA58C2-IgG4-CD28-MERTK CER03 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 75 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Leu Asn Gly Cys Ala Asn Pro Leu Gly Leu -5 1 5 10 Lys Asn Asn Ser Ile Pro Asp Lys Gln Ile Thr Ala Ser Ser Ser Tyr 15 20 25 Lys Thr Trp Gly Leu His Leu Phe Ser Trp Asn Pro Ser Tyr Ala Arg 30 35 40 Leu Asp Lys Gln Gly Asn Phe Asn Ala Trp Val Ala Gly Ser Tyr Gly 45 50 55 Asn Asp Gln Trp Leu Gln Val Asp Leu Gly Ser Ser Lys Glu Val Thr 60 65 70 Gly Ile Ile Thr Gln Gly Ala Arg Asn Phe Gly Ser Val Gln Phe Val 75 80 85 90 Ala Ser Tyr Lys Val Ala Tyr Ser Asn Asp Ser Ala Asn Trp Thr Glu 95 100 105 Tyr Gln Asp Pro Arg Thr Gly Ser Ser Lys Ile Phe Pro Gly Asn Trp 110 115 120 Asp Asn His Ser His Lys Lys Asn Leu Phe Glu Thr Pro Ile Leu Ala 125 130 135 Arg Tyr Val Arg Ile Leu Pro Val Ala Trp His Asn Arg Ile Ala Leu 140 145 150 Arg Leu Glu Leu Leu Gly Cys Glu Ser Lys Tyr Gly Pro Pro Cys Pro 155 160 165 170 Pro Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala 175 180 185 Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Ala 190 195 200 Leu Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu 205 210 215 Glu Asp Ser Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys 220 225 230 Arg Arg Ala Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu 235 240 245 250 Leu Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val 255 260 265 Leu Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly 270 275 280 Asn Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr 285 290 295 Met Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser 300 305 310 Glu Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu 315 320 325 330 Leu Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met 335 340 345 Val Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu 350 355 360 Tyr Ser Arg Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu 365 370 375 Leu Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn 380 385 390 Arg Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg 395 400 405 410 Asp Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile 415 420 425 Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val 430 435 440 Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys 445 450 455 Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg 460 465 470 Gly Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr 475 480 485 490 Leu Leu His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu 495 500 505 Leu Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg 510 515 520 Pro Thr Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser 525 530 535 Leu Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln 540 545 550 Leu Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly 555 560 565 570 Leu Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro 575 580 585 Gly Ala Ala Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu 590 595 600 Arg Glu Glu Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp 605 610 615 Val Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val 620 625 630 Leu Pro Glu Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His 635 640 645 650 Ser Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val 655 660 665 Asp Asp Ser Leu Glu Asp Ser Glu Val Leu Met 670 675 <210> SEQ ID NO 76 <211> LENGTH: 192 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rac1 <400> SEQUENCE: 76 Met Gln Ala Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys 1 5 10 15 Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Ala Phe Pro Gly Glu Tyr 20 25 30 Ile Pro Thr Val Phe Asp Asn Tyr Ser Ala Asn Val Met Val Asp Gly 35 40 45 Lys Pro Val Asn Leu Gly Leu Trp Asp Thr Ala Gly Gln Glu Asp Tyr 50 55 60 Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Asp Val Phe Leu Ile 65 70 75 80 Cys Phe Ser Leu Val Ser Pro Ala Ser Phe Glu Asn Val Arg Ala Lys 85 90 95 Trp Tyr Pro Glu Val Arg His His Cys Pro Asn Thr Pro Ile Ile Leu 100 105 110 Val Gly Thr Lys Leu Asp Leu Arg Asp Asp Lys Asp Thr Ile Glu Lys 115 120 125 Leu Lys Glu Lys Lys Leu Thr Pro Ile Thr Tyr Pro Gln Gly Leu Ala 130 135 140 Met Ala Lys Glu Ile Gly Ala Val Lys Tyr Leu Glu Cys Ser Ala Leu 145 150 155 160 Thr Gln Arg Gly Leu Lys Thr Val Phe Asp Glu Ala Ile Arg Ala Val 165 170 175 Leu Cys Pro Pro Pro Val Lys Lys Arg Lys Arg Lys Cys Leu Leu Leu 180 185 190 <210> SEQ ID NO 77 <211> LENGTH: 215 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rab5 <400> SEQUENCE: 77 Met Ala Ser Arg Gly Ala Thr Arg Pro Asn Gly Pro Asn Thr Gly Asn 1 5 10 15 Lys Ile Cys Gln Phe Lys Leu Val Leu Leu Gly Glu Ser Ala Val Gly 20 25 30 Lys Ser Ser Leu Val Leu Arg Phe Val Lys Gly Gln Phe His Glu Phe 35 40 45 Gln Glu Ser Thr Ile Gly Ala Ala Phe Leu Thr Gln Thr Val Cys Leu 50 55 60 Asp Asp Thr Thr Val Lys Phe Glu Ile Trp Asp Thr Ala Gly Gln Glu 65 70 75 80 Arg Tyr His Ser Leu Ala Pro Met Tyr Tyr Arg Gly Ala Gln Ala Ala 85 90 95 Ile Val Val Tyr Asp Ile Thr Asn Glu Glu Ser Phe Ala Arg Ala Lys 100 105 110 Asn Trp Val Lys Glu Leu Gln Arg Gln Ala Ser Pro Asn Ile Val Ile 115 120 125 Ala Leu Ser Gly Asn Lys Ala Asp Leu Ala Asn Lys Arg Ala Val Asp 130 135 140 Phe Gln Glu Ala Gln Ser Tyr Ala Asp Asp Asn Ser Leu Leu Phe Met 145 150 155 160 Glu Thr Ser Ala Lys Thr Ser Met Asn Val Asn Glu Ile Phe Met Ala 165 170 175 Ile Ala Lys Lys Leu Pro Lys Asn Glu Pro Gln Asn Pro Gly Ala Asn 180 185 190 Ser Ala Arg Gly Arg Gly Val Asp Leu Thr Glu Pro Thr Gln Pro Thr 195 200 205 Arg Asn Gln Cys Cys Ser Asn 210 215 <210> SEQ ID NO 78 <211> LENGTH: 155 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated MyD88 without TIR domain <400> SEQUENCE: 78 Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser 1 5 10 15 Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg 20 25 30 Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr 35 40 45 Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu 50 55 60 Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly 65 70 75 80 Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu 85 90 95 Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp 100 105 110 Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro 115 120 125 Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu 130 135 140 Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly 145 150 155 <210> SEQ ID NO 79 <211> LENGTH: 455 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-tMyD88 CER15 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 79 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly 430 <210> SEQ ID NO 80 <211> LENGTH: 596 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-MyD88 CER16 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 80 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly His Met Pro Glu Arg Phe Asp Ala Phe 430 435 440 Ile Cys Tyr Cys Pro Ser Asp Ile Gln Phe Val Gln Glu Met Ile Arg 445 450 455 Gln Leu Glu Gln Thr Asn Tyr Arg Leu Lys Leu Cys Val Ser Asp Arg 460 465 470 Asp Val Leu Pro Gly Thr Cys Val Trp Ser Ile Ala Ser Glu Leu Ile 475 480 485 490 Glu Lys Arg Cys Arg Arg Met Val Val Val Val Ser Asp Asp Tyr Leu 495 500 505 Gln Ser Lys Glu Cys Asp Phe Gln Thr Lys Phe Ala Leu Ser Leu Ser 510 515 520 Pro Gly Ala His Gln Lys Arg Leu Ile Pro Ile Lys Tyr Lys Ala Met 525 530 535 Lys Lys Glu Phe Pro Ser Ile Leu Arg Phe Ile Thr Val Cys Asp Tyr 540 545 550 Thr Asn Pro Cys Thr Lys Ser Trp Phe Trp Thr Arg Leu Ala Lys Ala 555 560 565 570 Leu Ser Leu Pro <210> SEQ ID NO 81 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: PEPTIDE <222> LOCATION: (0)...(0) <223> OTHER INFORMATION: DAP12 transmembrane domain <400> SEQUENCE: 81 Gly Val Leu Ala Gly Ile Val Met Gly Asp Leu Val Leu Thr Val Leu 1 5 10 15 Ile Ala Leu Ala Val 20 <210> SEQ ID NO 82 <211> LENGTH: 52 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: DAP12 signaling domain <400> SEQUENCE: 82 Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala 1 5 10 15 Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu 20 25 30 Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg 35 40 45 Pro Tyr Tyr Lys 50 <210> SEQ ID NO 83 <211> LENGTH: 740 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-Tyro3 CER08 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 83 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Leu Arg Lys Arg 270 275 280 Arg Lys Glu Thr Arg Phe Gly Gln Ala Phe Asp Ser Val Met Ala Arg 285 290 295 Gly Glu Pro Ala Val His Phe Arg Ala Ala Arg Ser Phe Asn Arg Glu 300 305 310 Arg Pro Glu Arg Ile Glu Ala Thr Leu Asp Ser Leu Gly Ile Ser Asp 315 320 325 330 Glu Leu Lys Glu Lys Leu Glu Asp Val Leu Ile Pro Glu Gln Gln Phe 335 340 345 Thr Leu Gly Arg Met Leu Gly Lys Gly Glu Phe Gly Ser Val Arg Glu 350 355 360 Ala Gln Leu Lys Gln Glu Asp Gly Ser Phe Val Lys Val Ala Val Lys 365 370 375 Met Leu Lys Ala Asp Ile Ile Ala Ser Ser Asp Ile Glu Glu Phe Leu 380 385 390 Arg Glu Ala Ala Cys Met Lys Glu Phe Asp His Pro His Val Ala Lys 395 400 405 410 Leu Val Gly Val Ser Leu Arg Ser Arg Ala Lys Gly Arg Leu Pro Ile 415 420 425 Pro Met Val Ile Leu Pro Phe Met Lys His Gly Asp Leu His Ala Phe 430 435 440 Leu Leu Ala Ser Arg Ile Gly Glu Asn Pro Phe Asn Leu Pro Leu Gln 445 450 455 Thr Leu Ile Arg Phe Met Val Asp Ile Ala Cys Gly Met Glu Tyr Leu 460 465 470 Ser Ser Arg Asn Phe Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met 475 480 485 490 Leu Ala Glu Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Arg 495 500 505 Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Cys Ala Ser Lys Leu 510 515 520 Pro Val Lys Trp Leu Ala Leu Glu Ser Leu Ala Asp Asn Leu Tyr Thr 525 530 535 Val Gln Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Met 540 545 550 Thr Arg Gly Gln Thr Pro Tyr Ala Gly Ile Glu Asn Ala Glu Ile Tyr 555 560 565 570 Asn Tyr Leu Ile Gly Gly Asn Arg Leu Lys Gln Pro Pro Glu Cys Met 575 580 585 Glu Asp Val Tyr Asp Leu Met Tyr Gln Cys Trp Ser Ala Asp Pro Lys 590 595 600 Gln Arg Pro Ser Phe Thr Cys Leu Arg Met Glu Leu Glu Asn Ile Leu 605 610 615 Gly Gln Leu Ser Val Leu Ser Ala Ser Gln Asp Pro Leu Tyr Ile Asn 620 625 630 Ile Glu Arg Ala Glu Glu Pro Thr Ala Gly Gly Ser Leu Glu Leu Pro 635 640 645 650 Gly Arg Asp Gln Pro Tyr Ser Gly Ala Gly Asp Gly Ser Gly Met Gly 655 660 665 Ala Val Gly Gly Thr Pro Ser Asp Cys Arg Tyr Ile Leu Thr Pro Gly 670 675 680 Gly Leu Ala Glu Gln Pro Gly Gln Ala Glu His Gln Pro Glu Ser Pro 685 690 695 Leu Asn Glu Thr Gln Arg Leu Leu Leu Leu Gln Gln Gly Leu Leu Pro 700 705 710 His Ser Ser Cys 715 <210> SEQ ID NO 84 <211> LENGTH: 352 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-DAP12 CER09 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 84 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Tyr Phe Leu Gly 270 275 280 Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys 285 290 295 Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln 300 305 310 Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 315 320 325 330 <210> SEQ ID NO 85 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcepsilonRIgamma transmembrane domain <400> SEQUENCE: 85 ctttgttaca ttctcgacgc gatattgttc ctttatggaa tagttttgac gctcctttat 60 tgc 63 <210> SEQ ID NO 86 <211> LENGTH: 352 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-DAP12-DAP12 CER10 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 86 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Gly Val Leu Ala Gly Ile Val Met Gly 255 260 265 Asp Leu Val Leu Thr Val Leu Ile Ala Leu Ala Val Tyr Phe Leu Gly 270 275 280 Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys 285 290 295 Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln 300 305 310 Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 315 320 325 330 <210> SEQ ID NO 87 <211> LENGTH: 722 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4-Axl CER11 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 87 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys 270 275 280 Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly 285 290 295 Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr 300 305 310 Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu 315 320 325 330 Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys 335 340 345 Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn 350 355 360 Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala 365 370 375 Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys 380 385 390 Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys 395 400 405 410 Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu 415 420 425 Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe 445 450 455 Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe 460 465 470 Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met 475 480 485 490 Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr 540 545 550 Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln 555 560 565 570 Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala 575 580 585 Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe 590 595 600 Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro 605 610 615 Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met Asp Glu Gly Gly 620 625 630 Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr 635 640 645 650 Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val 655 660 665 His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro 670 675 680 Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp 685 690 695 Gly Ala 700 <210> SEQ ID NO 88 <211> LENGTH: 42 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcepsilonRIgamma signaling domain <400> SEQUENCE: 88 Arg Leu Lys Ile Gln Val Arg Lys Ala Ala Ile Thr Ser Tyr Glu Lys 1 5 10 15 Ser Asp Gly Val Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr 20 25 30 Glu Thr Leu Lys His Glu Lys Pro Pro Gln 35 40 <210> SEQ ID NO 89 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcepsilonRIgamma transmembrane domain <400> SEQUENCE: 89 Leu Cys Tyr Ile Leu Asp Ala Ile Leu Phe Leu Tyr Gly Ile Val Leu 1 5 10 15 Thr Leu Leu Tyr Cys 20 <210> SEQ ID NO 90 <211> LENGTH: 342 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4- FcepsilonRIgamma CER12 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 90 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp 1 5 10 15 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu 20 25 30 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 35 40 45 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 50 55 60 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 65 70 75 80 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 85 90 95 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 100 105 110 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 115 120 125 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 130 135 140 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 145 150 155 160 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 165 170 175 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 180 185 190 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 195 200 205 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 210 215 220 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 225 230 235 240 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 245 250 255 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 260 265 270 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 275 280 285 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Arg Leu Lys Ile 290 295 300 Gln Val Arg Lys Ala Ala Ile Thr Ser Tyr Glu Lys Ser Asp Gly Val 305 310 315 320 Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr Glu Thr Leu Lys 325 330 335 His Glu Lys Pro Pro Gln 340 <210> SEQ ID NO 91 <211> LENGTH: 342 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4- Fc(epsilon)RI(gamma)-Fc(epsilon)RI(gamma) CER13 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 91 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Leu Cys Tyr Ile Leu Asp Ala Ile Leu 255 260 265 Phe Leu Tyr Gly Ile Val Leu Thr Leu Leu Tyr Cys Arg Leu Lys Ile 270 275 280 Gln Val Arg Lys Ala Ala Ile Thr Ser Tyr Glu Lys Ser Asp Gly Val 285 290 295 Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr Glu Thr Leu Lys 300 305 310 His Glu Lys Pro Pro Gln 315 320 <210> SEQ ID NO 92 <211> LENGTH: 86 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: NFAM1 signaling domain <400> SEQUENCE: 92 Leu Trp Asn Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg 1 5 10 15 Lys Cys Pro Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser 20 25 30 Glu Ser Val Tyr Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala 35 40 45 Cys Ile Glu Asn Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro 50 55 60 Leu Ser Gln Glu Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn 65 70 75 80 Leu Val Tyr Glu Asn Leu 85 <210> SEQ ID NO 93 <211> LENGTH: 386 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4-NFAM1 CER25 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 93 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Leu Trp Asn Lys 270 275 280 Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp 285 290 295 Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr 300 305 310 Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn 315 320 325 330 Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu 335 340 345 Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu 350 355 360 Asn Leu <210> SEQ ID NO 94 <211> LENGTH: 85 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BaFFR signaling domain <400> SEQUENCE: 94 Ser Trp Arg Arg Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu 1 5 10 15 Ala Pro Asp Gly Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile 20 25 30 Ile Leu Ser Pro Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro 35 40 45 Pro Gly Glu Asp Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val 50 55 60 Pro Ala Thr Glu Leu Gly Ser Thr Glu Leu Val Thr Thr Lys Thr Ala 65 70 75 80 Gly Pro Glu Gln Gln 85 <210> SEQ ID NO 95 <211> LENGTH: 540 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-BaFFR CER85 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 95 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Ser Trp Arg Arg Arg Gln Arg Arg Leu 430 435 440 Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly Asp Lys Asp Ala Pro 445 450 455 Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro Gly Ile Ser Asp Ala 460 465 470 Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp Pro Gly Thr Thr Pro 475 480 485 490 Pro Gly His Ser Val Pro Val Pro Ala Thr Glu Leu Gly Ser Thr Glu 495 500 505 Leu Val Thr Thr Lys Thr Ala Gly Pro Glu Gln Gln 510 515 <210> SEQ ID NO 96 <211> LENGTH: 507 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-Dap12 CER86 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 96 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Tyr Phe Leu Gly Arg Leu Val Pro Arg 430 435 440 Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu 445 450 455 Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr 460 465 470 Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 475 480 485 <210> SEQ ID NO 97 <211> LENGTH: 29 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD79b signaling domain <400> SEQUENCE: 97 Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly Leu Asp 1 5 10 15 Ile Asp Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu 20 25 <210> SEQ ID NO 98 <211> LENGTH: 484 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-CD79b CER89 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 98 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Asp Ser Lys Ala Gly Met Glu Glu Asp 430 435 440 His Thr Tyr Glu Gly Leu Asp Ile Asp Gln Thr Ala Thr Tyr Glu Asp 445 450 455 Ile Val Thr Leu 460 <210> SEQ ID NO 99 <211> LENGTH: 465 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated MyD88 signaling domain <400> SEQUENCE: 99 atggctgcag gaggtcccgg cgcggggtct gcggccccgg tctcctccac atcctccctt 60 cccctggctg ctctcaacat gcgagtgcgg cgccgcctgt ctctgttctt gaacgtgcgg 120 acacaggtgg cggccgactg gaccgcgctg gcggaggaga tggactttga gtacttggag 180 atccggcaac tggagacaca agcggacccc actggcaggc tgctggacgc ctggcaggga 240 cgccctggcg cctctgtagg ccgactgctc gagctgctta ccaagctggg ccgcgacgac 300 gtgctgctgg agctgggacc cagcattgag gaggattgcc aaaagtatat cttgaagcag 360 cagcaggagg aggctgagaa gcctttacag gtggccgctg tagacagcag tgtcccacgg 420 acagcagagc tggcgggcat caccacactt gatgaccccc tgggg 465 <210> SEQ ID NO 100 <211> LENGTH: 541 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-NFAM1 CER90 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 100 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Leu Trp Asn Lys Lys Arg Met Arg Gly 430 435 440 Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala Ser 445 450 455 Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr Thr Ala Leu Gln Arg 460 465 470 Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn Glu Asp Gly Ser Ser 475 480 485 490 Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu Arg Pro His Arg Phe 495 500 505 Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu Asn Leu 510 515 <210> SEQ ID NO 101 <211> LENGTH: 805 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-MerTk-CD79b CER95 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 101 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Asp Ser Lys Ala Gly Met Glu Glu 750 755 760 Asp His Thr Tyr Glu Gly Leu Asp Ile Asp Gln Thr Ala Thr Tyr Glu 765 770 775 Asp Ile Val Thr Leu 780 <210> SEQ ID NO 102 <211> LENGTH: 862 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-MerTk-NFAM1 CER96 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 102 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Leu Trp Asn Lys Lys Arg Met Arg 750 755 760 Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala 765 770 775 Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr Thr Ala Leu Gln 780 785 790 Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn Glu Asp Gly Ser 795 800 805 810 Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu Arg Pro His Arg 815 820 825 Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu Asn Leu 830 835 840 <210> SEQ ID NO 103 <211> LENGTH: 861 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-MERTK-BAFFR CER93 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 103 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Ser Trp Arg Arg Arg Gln Arg Arg 750 755 760 Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly Asp Lys Asp Ala 765 770 775 Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro Gly Ile Ser Asp 780 785 790 Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp Pro Gly Thr Thr 795 800 805 810 Pro Pro Gly His Ser Val Pro Val Pro Ala Thr Glu Leu Gly Ser Thr 815 820 825 Glu Leu Val Thr Thr Lys Thr Ala Gly Pro Glu Gln Gln 830 835 <210> SEQ ID NO 104 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P2A self-cleaving peptide <400> SEQUENCE: 104 Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 1 5 10 15 Pro Gly Pro <210> SEQ ID NO 105 <211> LENGTH: 692 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-P2A-Rab5a CER91 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 105 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Gly Ser Gly Ala Thr Asn Phe Ser Leu 430 435 440 Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Ala Ser 445 450 455 Arg Gly Ala Thr Arg Pro Asn Gly Pro Asn Thr Gly Asn Lys Ile Cys 460 465 470 Gln Phe Lys Leu Val Leu Leu Gly Glu Ser Ala Val Gly Lys Ser Ser 475 480 485 490 Leu Val Leu Arg Phe Val Lys Gly Gln Phe His Glu Phe Gln Glu Ser 495 500 505 Thr Ile Gly Ala Ala Phe Leu Thr Gln Thr Val Cys Leu Asp Asp Thr 510 515 520 Thr Val Lys Phe Glu Ile Trp Asp Thr Ala Gly Gln Glu Arg Tyr His 525 530 535 Ser Leu Ala Pro Met Tyr Tyr Arg Gly Ala Gln Ala Ala Ile Val Val 540 545 550 Tyr Asp Ile Thr Asn Glu Glu Ser Phe Ala Arg Ala Lys Asn Trp Val 555 560 565 570 Lys Glu Leu Gln Arg Gln Ala Ser Pro Asn Ile Val Ile Ala Leu Ser 575 580 585 Gly Asn Lys Ala Asp Leu Ala Asn Lys Arg Ala Val Asp Phe Gln Glu 590 595 600 Ala Gln Ser Tyr Ala Asp Asp Asn Ser Leu Leu Phe Met Glu Thr Ser 605 610 615 Ala Lys Thr Ser Met Asn Val Asn Glu Ile Phe Met Ala Ile Ala Lys 620 625 630 Lys Leu Pro Lys Asn Glu Pro Gln Asn Pro Gly Ala Asn Ser Ala Arg 635 640 645 650 Gly Arg Gly Val Asp Leu Thr Glu Pro Thr Gln Pro Thr Arg Asn Gln 655 660 665 Cys Cys Ser Asn 670 <210> SEQ ID NO 106 <211> LENGTH: 264 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: mesothelin specific scFv derived from M912 antibody <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 106 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser -5 1 5 10 Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 15 20 25 Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 30 35 40 Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val 45 50 55 Pro Ser Gly Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 60 65 70 Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 75 80 85 90 Ser Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 95 100 105 Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 110 115 120 Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser 125 130 135 Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser 140 145 150 Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 155 160 165 170 Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro 175 180 185 Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln 190 195 200 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 205 210 215 Tyr Cys Ala Arg Glu Gly Lys Asn Gly Ala Phe Asp Ile Trp Gly Gln 220 225 230 Gly Thr Met Val Thr Val Ser Ser 235 240 <210> SEQ ID NO 107 <211> LENGTH: 452 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: M912 scFv-IgG4 spacer-Tim4 TM-tMyD88 CER50 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 107 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser -5 1 5 10 Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 15 20 25 Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 30 35 40 Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val 45 50 55 Pro Ser Gly Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 60 65 70 Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 75 80 85 90 Ser Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 95 100 105 Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 110 115 120 Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser 125 130 135 Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser 140 145 150 Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 155 160 165 170 Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro 175 180 185 Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln 190 195 200 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 205 210 215 Tyr Cys Ala Arg Glu Gly Lys Asn Gly Ala Phe Asp Ile Trp Gly Gln 220 225 230 Gly Thr Met Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys 235 240 245 250 Pro Pro Cys Pro Ile Leu Ile Ile Ala Cys Cys Val Gly Phe Val Leu 255 260 265 Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly Gly Pro Gly 270 275 280 Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu Pro Leu Ala 285 290 295 Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe Leu Asn Val 300 305 310 Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu Glu Met Asp 315 320 325 330 Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala Asp Pro Thr 335 340 345 Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala Ser Val Gly 350 355 360 Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp Val Leu Leu 365 370 375 Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr Ile Leu Lys 380 385 390 Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala Ala Val Asp 395 400 405 410 Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr Thr Leu Asp 415 420 425 Asp Pro Leu Gly 430 <210> SEQ ID NO 108 <400> SEQUENCE: 108 000 <210> SEQ ID NO 109 <400> SEQUENCE: 109 000 <210> SEQ ID NO 110 <400> SEQUENCE: 110 000 <210> SEQ ID NO 111 <400> SEQUENCE: 111 000 <210> SEQ ID NO 112 <400> SEQUENCE: 112 000 <210> SEQ ID NO 113 <400> SEQUENCE: 113 000 <210> SEQ ID NO 114 <211> LENGTH: 57 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 114 Lys Leu Leu Val Thr Ile His Asp Arg Arg Glu Phe Ala Lys Phe Gln 1 5 10 15 Ser Glu Arg Ser Arg Ala Arg Tyr Glu Met Ala Ser Asn Pro Leu Tyr 20 25 30 Arg Lys Pro Ile Ser Thr His Thr Val Asp Phe Thr Phe Asn Lys Phe 35 40 45 Asn Lys Ser Tyr Asn Gly Thr Val Asp 50 55 <210> SEQ ID NO 115 <211> LENGTH: 279 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 115 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr 255 <210> SEQ ID NO 116 <211> LENGTH: 829 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CER96 with truncated NFAM1 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 116 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Leu Trp Asn Lys Lys Arg Met Arg 750 755 760 Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala 765 770 775 Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr Thr Ala Leu Gln 780 785 790 Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn Glu 795 800 805 <210> SEQ ID NO 117 <211> LENGTH: 918 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 binding domain <400> SEQUENCE: 117 Ala Ala Gly Ala Asp Ala Gly Pro Gly Pro Glu Pro Cys Ala Thr Leu 1 5 10 15 Val Gln Gly Lys Phe Phe Gly Tyr Phe Ser Ala Ala Ala Val Phe Pro 20 25 30 Ala Asn Ala Ser Arg Cys Ser Trp Thr Leu Arg Asn Pro Asp Pro Arg 35 40 45 Arg Tyr Thr Leu Tyr Met Lys Val Ala Lys Ala Pro Val Pro Cys Ser 50 55 60 Gly Pro Gly Arg Val Arg Thr Tyr Gln Phe Asp Ser Phe Leu Glu Ser 65 70 75 80 Thr Arg Thr Tyr Leu Gly Val Glu Ser Phe Asp Glu Val Leu Arg Leu 85 90 95 Cys Asp Pro Ser Ala Pro Leu Ala Phe Leu Gln Ala Ser Lys Gln Phe 100 105 110 Leu Gln Met Arg Arg Gln Gln Pro Pro Gln His Asp Gly Leu Arg Pro 115 120 125 Arg Ala Gly Pro Pro Gly Pro Thr Asp Asp Phe Ser Val Glu Tyr Leu 130 135 140 Val Val Gly Asn Arg Asn Pro Ser Arg Ala Ala Cys Gln Met Leu Cys 145 150 155 160 Arg Trp Leu Asp Ala Cys Leu Ala Gly Ser Arg Ser Ser His Pro Cys 165 170 175 Gly Ile Met Gln Thr Pro Cys Ala Cys Leu Gly Gly Glu Ala Gly Gly 180 185 190 Pro Ala Ala Gly Pro Leu Ala Pro Arg Gly Asp Val Cys Leu Arg Asp 195 200 205 Ala Val Ala Gly Gly Pro Glu Asn Cys Leu Thr Ser Leu Thr Gln Asp 210 215 220 Arg Gly Gly His Gly Ala Thr Gly Gly Trp Lys Leu Trp Ser Leu Trp 225 230 235 240 Gly Glu Cys Thr Arg Asp Cys Gly Gly Gly Leu Gln Thr Arg Thr Arg 245 250 255 Thr Cys Leu Pro Ala Pro Gly Val Glu Gly Gly Gly Cys Glu Gly Val 260 265 270 Leu Glu Glu Gly Arg Gln Cys Asn Arg Glu Ala Cys Gly Pro Ala Gly 275 280 285 Arg Thr Ser Ser Arg Ser Gln Ser Leu Arg Ser Thr Asp Ala Arg Arg 290 295 300 Arg Glu Glu Leu Gly Asp Glu Leu Gln Gln Phe Gly Phe Pro Ala Pro 305 310 315 320 Gln Thr Gly Asp Pro Ala Ala Glu Glu Trp Ser Pro Trp Ser Val Cys 325 330 335 Ser Ser Thr Cys Gly Glu Gly Trp Gln Thr Arg Thr Arg Phe Cys Val 340 345 350 Ser Ser Ser Tyr Ser Thr Gln Cys Ser Gly Pro Leu Arg Glu Gln Arg 355 360 365 Leu Cys Asn Asn Ser Ala Val Cys Pro Val His Gly Ala Trp Asp Glu 370 375 380 Trp Ser Pro Trp Ser Leu Cys Ser Ser Thr Cys Gly Arg Gly Phe Arg 385 390 395 400 Asp Arg Thr Arg Thr Cys Arg Pro Pro Gln Phe Gly Gly Asn Pro Cys 405 410 415 Glu Gly Pro Glu Lys Gln Thr Lys Phe Cys Asn Ile Ala Leu Cys Pro 420 425 430 Gly Arg Ala Val Asp Gly Asn Trp Asn Glu Trp Ser Ser Trp Ser Ala 435 440 445 Cys Ser Ala Ser Cys Ser Gln Gly Arg Gln Gln Arg Thr Arg Glu Cys 450 455 460 Asn Gly Pro Ser Tyr Gly Gly Ala Glu Cys Gln Gly His Trp Val Glu 465 470 475 480 Thr Arg Asp Cys Phe Leu Gln Gln Cys Pro Val Asp Gly Lys Trp Gln 485 490 495 Ala Trp Ala Ser Trp Gly Ser Cys Ser Val Thr Cys Gly Ala Gly Ser 500 505 510 Gln Arg Arg Glu Arg Val Cys Ser Gly Pro Phe Phe Gly Gly Ala Ala 515 520 525 Cys Gln Gly Pro Gln Asp Glu Tyr Arg Gln Cys Gly Thr Gln Arg Cys 530 535 540 Pro Glu Pro His Glu Ile Cys Asp Glu Asp Asn Phe Gly Ala Val Ile 545 550 555 560 Trp Lys Glu Thr Pro Ala Gly Glu Val Ala Ala Val Arg Cys Pro Arg 565 570 575 Asn Ala Thr Gly Leu Ile Leu Arg Arg Cys Glu Leu Asp Glu Glu Gly 580 585 590 Ile Ala Tyr Trp Glu Pro Pro Thr Tyr Ile Arg Cys Val Ser Ile Asp 595 600 605 Tyr Arg Asn Ile Gln Met Met Thr Arg Glu His Leu Ala Lys Ala Gln 610 615 620 Arg Gly Leu Pro Gly Glu Gly Val Ser Glu Val Ile Gln Thr Leu Val 625 630 635 640 Glu Ile Ser Gln Asp Gly Thr Ser Tyr Ser Gly Asp Leu Leu Ser Thr 645 650 655 Ile Asp Val Leu Arg Asn Met Thr Glu Ile Phe Arg Arg Ala Tyr Tyr 660 665 670 Ser Pro Thr Pro Gly Asp Val Gln Asn Phe Val Gln Ile Leu Ser Asn 675 680 685 Leu Leu Ala Glu Glu Asn Arg Asp Lys Trp Glu Glu Ala Gln Leu Ala 690 695 700 Gly Pro Asn Ala Lys Glu Leu Phe Arg Leu Val Glu Asp Phe Val Asp 705 710 715 720 Val Ile Gly Phe Arg Met Lys Asp Leu Arg Asp Ala Tyr Gln Val Thr 725 730 735 Asp Asn Leu Val Leu Ser Ile His Lys Leu Pro Ala Ser Gly Ala Thr 740 745 750 Asp Ile Ser Phe Pro Met Lys Gly Trp Arg Ala Thr Gly Asp Trp Ala 755 760 765 Lys Val Pro Glu Asp Arg Val Thr Val Ser Lys Ser Val Phe Ser Thr 770 775 780 Gly Leu Thr Glu Ala Asp Glu Ala Ser Val Phe Val Val Gly Thr Val 785 790 795 800 Leu Tyr Arg Asn Leu Gly Ser Phe Leu Ala Leu Gln Arg Asn Thr Thr 805 810 815 Val Leu Asn Ser Lys Val Ile Ser Val Thr Val Lys Pro Pro Pro Arg 820 825 830 Ser Leu Arg Thr Pro Leu Glu Ile Glu Phe Ala His Met Tyr Asn Gly 835 840 845 Thr Thr Asn Gln Thr Cys Ile Leu Trp Asp Glu Thr Asp Val Pro Ser 850 855 860 Ser Ser Ala Pro Pro Gln Leu Gly Pro Trp Ser Trp Arg Gly Cys Arg 865 870 875 880 Thr Val Pro Leu Asp Ala Leu Arg Thr Arg Cys Leu Cys Asp Arg Leu 885 890 895 Ser Thr Phe Ala Ile Leu Ala Gln Leu Ser Ala Asp Ala Asn Met Glu 900 905 910 Lys Ala Thr Leu Pro Ser 915 <210> SEQ ID NO 118 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 transmembrane domain <400> SEQUENCE: 118 Gly Val Val Ile Ile Val Ile Leu Leu Ile Leu Thr Gly Ala Gly Leu 1 5 10 15 Ala Ala Tyr Phe Phe 20 <210> SEQ ID NO 119 <211> LENGTH: 46 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 signaling domain <400> SEQUENCE: 119 Tyr Lys Lys Arg Arg Val His Leu Pro Gln Glu Gly Ala Phe Glu Asn 1 5 10 15 Thr Leu Tyr Phe Asn Ser Gln Ser Ser Pro Gly Thr Ser Asp Met Lys 20 25 30 Asp Leu Val Gly Asn Ile Glu Gln Asn Glu His Ser Val Ile 35 40 45 <210> SEQ ID NO 120 <211> LENGTH: 727 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ELMO <400> SEQUENCE: 120 Met Pro Pro Pro Ala Asp Ile Val Lys Val Ala Ile Glu Trp Pro Gly 1 5 10 15 Ala Tyr Pro Lys Leu Met Glu Ile Asp Gln Lys Lys Pro Leu Ser Ala 20 25 30 Ile Ile Lys Glu Val Cys Asp Gly Trp Ser Leu Ala Asn His Glu Tyr 35 40 45 Phe Ala Leu Gln His Ala Asp Ser Ser Asn Phe Tyr Ile Thr Glu Lys 50 55 60 Asn Arg Asn Glu Ile Lys Asn Gly Thr Ile Leu Arg Leu Thr Thr Ser 65 70 75 80 Pro Ala Gln Asn Ala Gln Gln Leu His Glu Arg Ile Gln Ser Ser Ser 85 90 95 Met Asp Ala Lys Leu Glu Ala Leu Lys Asp Leu Ala Ser Leu Ser Arg 100 105 110 Asp Val Thr Phe Ala Gln Glu Phe Ile Asn Leu Asp Gly Ile Ser Leu 115 120 125 Leu Thr Gln Met Val Glu Ser Gly Thr Glu Arg Tyr Gln Lys Leu Gln 130 135 140 Lys Ile Met Lys Pro Cys Phe Gly Asp Met Leu Ser Phe Thr Leu Thr 145 150 155 160 Ala Phe Val Glu Leu Met Asp His Gly Ile Val Ser Trp Asp Thr Phe 165 170 175 Ser Val Ala Phe Ile Lys Lys Ile Ala Ser Phe Val Asn Lys Ser Ala 180 185 190 Ile Asp Ile Ser Ile Leu Gln Arg Ser Leu Ala Ile Leu Glu Ser Met 195 200 205 Val Leu Asn Ser His Asp Leu Tyr Gln Lys Val Ala Gln Glu Ile Thr 210 215 220 Ile Gly Gln Leu Ile Pro His Leu Gln Gly Ser Asp Gln Glu Ile Gln 225 230 235 240 Thr Tyr Thr Ile Ala Val Ile Asn Ala Leu Phe Leu Lys Ala Pro Asp 245 250 255 Glu Arg Arg Gln Glu Met Ala Asn Ile Leu Ala Gln Lys Gln Leu Arg 260 265 270 Ser Ile Ile Leu Thr His Val Ile Arg Ala Gln Arg Ala Ile Asn Asn 275 280 285 Glu Met Ala His Gln Leu Tyr Val Leu Gln Val Leu Thr Phe Asn Leu 290 295 300 Leu Glu Asp Arg Met Met Thr Lys Met Asp Pro Gln Asp Gln Ala Gln 305 310 315 320 Arg Asp Ile Ile Phe Glu Leu Arg Arg Ile Ala Phe Asp Ala Glu Ser 325 330 335 Glu Pro Asn Asn Ser Ser Gly Ser Met Glu Lys Arg Lys Ser Met Tyr 340 345 350 Thr Arg Asp Tyr Lys Lys Leu Gly Phe Ile Asn His Val Asn Pro Ala 355 360 365 Met Asp Phe Thr Gln Thr Pro Pro Gly Met Leu Ala Leu Asp Asn Met 370 375 380 Leu Tyr Phe Ala Lys His His Gln Asp Ala Tyr Ile Arg Ile Val Leu 385 390 395 400 Glu Asn Ser Ser Arg Glu Asp Lys His Glu Cys Pro Phe Gly Arg Ser 405 410 415 Ser Ile Glu Leu Thr Lys Met Leu Cys Glu Ile Leu Lys Val Gly Glu 420 425 430 Leu Pro Ser Glu Thr Cys Asn Asp Phe His Pro Met Phe Phe Thr His 435 440 445 Asp Arg Ser Phe Glu Glu Phe Phe Cys Ile Cys Ile Gln Leu Leu Asn 450 455 460 Lys Thr Trp Lys Glu Met Arg Ala Thr Ser Glu Asp Phe Asn Lys Val 465 470 475 480 Met Gln Val Val Lys Glu Gln Val Met Arg Ala Leu Thr Thr Lys Pro 485 490 495 Ser Ser Leu Asp Gln Phe Lys Ser Lys Leu Gln Asn Leu Ser Tyr Thr 500 505 510 Glu Ile Leu Lys Ile Arg Gln Ser Glu Arg Met Asn Gln Glu Asp Phe 515 520 525 Gln Ser Arg Pro Ile Leu Glu Leu Lys Glu Lys Ile Gln Pro Glu Ile 530 535 540 Leu Glu Leu Ile Lys Gln Gln Arg Leu Asn Arg Leu Val Glu Gly Thr 545 550 555 560 Cys Phe Arg Lys Leu Asn Ala Arg Arg Arg Gln Asp Lys Phe Trp Tyr 565 570 575 Cys Arg Leu Ser Pro Asn His Lys Val Leu His Tyr Gly Asp Leu Glu 580 585 590 Glu Ser Pro Gln Gly Glu Val Pro His Asp Ser Leu Gln Asp Lys Leu 595 600 605 Pro Val Ala Asp Ile Lys Ala Val Val Thr Gly Lys Asp Cys Pro His 610 615 620 Met Lys Glu Lys Gly Ala Leu Lys Gln Asn Lys Glu Val Leu Glu Leu 625 630 635 640 Ala Phe Ser Ile Leu Tyr Asp Ser Asn Cys Gln Leu Asn Phe Ile Ala 645 650 655 Pro Asp Lys His Glu Tyr Cys Ile Trp Thr Asp Gly Leu Asn Ala Leu 660 665 670 Leu Gly Lys Asp Met Met Ser Asp Leu Thr Arg Asn Asp Leu Asp Thr 675 680 685 Leu Leu Ser Met Glu Ile Lys Leu Arg Leu Leu Asp Leu Glu Asn Ile 690 695 700 Gln Ile Pro Asp Ala Pro Pro Pro Ile Pro Lys Glu Pro Ser Asn Tyr 705 710 715 720 Asp Phe Val Tyr Asp Cys Asn 725 <210> SEQ ID NO 121 <211> LENGTH: 285 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated EGFR <400> SEQUENCE: 121 Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu 1 5 10 15 Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile 20 25 30 Ser Gly Asp Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe 35 40 45 Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr 50 55 60 Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn 65 70 75 80 Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg 85 90 95 Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile 100 105 110 Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val 115 120 125 Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp 130 135 140 Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn 145 150 155 160 Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu 165 170 175 Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser 180 185 190 Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu 195 200 205 Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln 210 215 220 Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly 225 230 235 240 Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro 245 250 255 His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr 260 265 270 Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His 275 280 285 <210> SEQ ID NO 122 <211> LENGTH: 207 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rab7 <400> SEQUENCE: 122 Met Thr Ser Arg Lys Lys Val Leu Leu Lys Val Ile Ile Leu Gly Asp 1 5 10 15 Ser Gly Val Gly Lys Thr Ser Leu Met Asn Gln Tyr Val Asn Lys Lys 20 25 30 Phe Ser Asn Gln Tyr Lys Ala Thr Ile Gly Ala Asp Phe Leu Thr Lys 35 40 45 Glu Val Met Val Asp Asp Arg Leu Val Thr Met Gln Ile Trp Asp Thr 50 55 60 Ala Gly Gln Glu Arg Phe Gln Ser Leu Gly Val Ala Phe Tyr Arg Gly 65 70 75 80 Ala Asp Cys Cys Val Leu Val Phe Asp Val Thr Ala Pro Asn Thr Phe 85 90 95 Lys Thr Leu Asp Ser Trp Arg Asp Glu Phe Leu Ile Gln Ala Ser Pro 100 105 110 Arg Asp Pro Glu Asn Phe Pro Phe Val Val Leu Gly Asn Lys Ile Asp 115 120 125 Leu Glu Asn Arg Gln Val Ala Thr Lys Arg Ala Gln Ala Trp Cys Tyr 130 135 140 Ser Lys Asn Asn Ile Pro Tyr Phe Glu Thr Ser Ala Lys Glu Ala Ile 145 150 155 160 Asn Val Glu Gln Ala Phe Gln Thr Ile Ala Arg Asn Ala Leu Lys Gln 165 170 175 Glu Thr Glu Val Glu Leu Tyr Asn Glu Phe Pro Glu Pro Ile Lys Leu 180 185 190 Asp Lys Asn Asp Arg Ala Lys Ala Ser Ala Glu Ser Cys Ser Cys 195 200 205 <210> SEQ ID NO 123 <211> LENGTH: 184 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rap1A <400> SEQUENCE: 123 Met Arg Glu Tyr Lys Leu Val Val Leu Gly Ser Gly Gly Val Gly Lys 1 5 10 15 Ser Ala Leu Thr Val Gln Phe Val Gln Gly Ile Phe Val Glu Lys Tyr 20 25 30 Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Glu Val Asp Cys 35 40 45 Gln Gln Cys Met Leu Glu Ile Leu Asp Thr Ala Gly Thr Glu Gln Phe 50 55 60 Thr Ala Met Arg Asp Leu Tyr Met Lys Asn Gly Gln Gly Phe Ala Leu 65 70 75 80 Val Tyr Ser Ile Thr Ala Gln Ser Thr Phe Asn Asp Leu Gln Asp Leu 85 90 95 Arg Glu Gln Ile Leu Arg Val Lys Asp Thr Glu Asp Val Pro Met Ile 100 105 110 Leu Val Gly Asn Lys Cys Asp Leu Glu Asp Glu Arg Val Val Gly Lys 115 120 125 Glu Gln Gly Gln Asn Leu Ala Arg Gln Trp Cys Asn Cys Ala Phe Leu 130 135 140 Glu Ser Ser Ala Lys Ser Lys Ile Asn Val Asn Glu Ile Phe Tyr Asp 145 150 155 160 Leu Val Arg Gln Ile Asn Arg Lys Thr Pro Val Glu Lys Lys Lys Pro 165 170 175 Lys Lys Lys Ser Cys Leu Leu Leu 180 <210> SEQ ID NO 124 <211> LENGTH: 193 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: RhoA <400> SEQUENCE: 124 Met Ala Ala Ile Arg Lys Lys Leu Val Ile Val Gly Asp Gly Ala Cys 1 5 10 15 Gly Lys Thr Cys Leu Leu Ile Val Phe Ser Lys Asp Gln Phe Pro Glu 20 25 30 Val Tyr Val Pro Thr Val Phe Glu Asn Tyr Val Ala Asp Ile Glu Val 35 40 45 Asp Gly Lys Gln Val Glu Leu Ala Leu Trp Asp Thr Ala Gly Gln Glu 50 55 60 Asp Tyr Asp Arg Leu Arg Pro Leu Ser Tyr Pro Asp Thr Asp Val Ile 65 70 75 80 Leu Met Cys Phe Ser Ile Asp Ser Pro Asp Ser Leu Glu Asn Ile Pro 85 90 95 Glu Lys Trp Thr Pro Glu Val Lys His Phe Cys Pro Asn Val Pro Ile 100 105 110 Ile Leu Val Gly Asn Lys Lys Asp Leu Arg Asn Asp Glu His Thr Arg 115 120 125 Arg Glu Leu Ala Lys Met Lys Gln Glu Pro Val Lys Pro Glu Glu Gly 130 135 140 Arg Asp Met Ala Asn Arg Ile Gly Ala Phe Gly Tyr Met Glu Cys Ser 145 150 155 160 Ala Lys Thr Lys Asp Gly Val Arg Glu Val Phe Glu Met Ala Thr Arg 165 170 175 Ala Ala Leu Gln Ala Arg Arg Gly Lys Lys Lys Ser Gly Cys Leu Val 180 185 190 Leu <210> SEQ ID NO 125 <211> LENGTH: 191 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CDC42 <400> SEQUENCE: 125 Met Gln Thr Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys 1 5 10 15 Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Lys Phe Pro Ser Glu Tyr 20 25 30 Val Pro Thr Val Phe Asp Asn Tyr Ala Val Thr Val Met Ile Gly Gly 35 40 45 Glu Pro Tyr Thr Leu Gly Leu Phe Asp Thr Ala Gly Gln Glu Asp Tyr 50 55 60 Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Asp Val Phe Leu Val 65 70 75 80 Cys Phe Ser Val Val Ser Pro Ser Ser Phe Glu Asn Val Lys Glu Lys 85 90 95 Trp Val Pro Glu Ile Thr His His Cys Pro Lys Thr Pro Phe Leu Leu 100 105 110 Val Gly Thr Gln Ile Asp Leu Arg Asp Asp Pro Ser Thr Ile Glu Lys 115 120 125 Leu Ala Lys Asn Lys Gln Lys Pro Ile Thr Pro Glu Thr Ala Glu Lys 130 135 140 Leu Ala Arg Asp Leu Lys Ala Val Lys Tyr Val Glu Cys Ser Ala Leu 145 150 155 160 Thr Gln Lys Gly Leu Lys Asn Val Phe Asp Glu Ala Ile Leu Ala Ala 165 170 175 Leu Glu Pro Pro Glu Pro Lys Lys Ser Arg Arg Cys Val Leu Leu 180 185 190 <210> SEQ ID NO 126 <211> LENGTH: 255 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAFFR signaling domain <400> SEQUENCE: 126 tcctggagac ggcgacaaag gcgcttgcgc ggcgcatcat ccgcagaggc gcccgacggc 60 gataaggacg cgcccgaacc ccttgataaa gttattatct tgtcaccggg aatttctgac 120 gctacggcac ccgcgtggcc tcctccgggc gaagatcctg gtacgacacc ccctggacac 180 agtgttcccg tgcccgcgac agagctcggt agcacagaac tggtgaccac aaagacggcg 240 ggaccggaac agcaa 255 <210> SEQ ID NO 127 <211> LENGTH: 156 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: DAP12 signaling domain <400> SEQUENCE: 127 tattttctgg gaaggctcgt tcctagaggt agaggtgctg ccgaagcagc gacgcgcaaa 60 cagaggatta ctgaaacgga gtctccctac caagagctgc aaggccagag gtcagatgtc 120 tattcagact tgaacacaca aaggccatac tacaaa 156 <210> SEQ ID NO 128 <211> LENGTH: 135 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD79b signaling domain <400> SEQUENCE: 128 gacagtaaag ccgggatgga agaggaccac acatacgagg ggcttgacat agatcaaaca 60 gcgacatacg aagacatcgt aaccttgcgg actggagagg ttaaatggtc agtcggagaa 120 caccccggcc aagaa 135 <210> SEQ ID NO 129 <211> LENGTH: 258 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: NFAM1 signaling domain <400> SEQUENCE: 129 ctctggaata aaaagaggat gcgcggcccg ggaaaagacc caacgagaaa gtgtcccgat 60 ccccgcagtg cgtcaagccc caagcagcat ccttccgaaa gcgtatatac ggcacttcaa 120 cgccgggaaa cggaggtata tgcgtgtatt gagaacgagg acgggtcatc cccgaccgcc 180 aaacagtccc ctctcagcca agagcgacct cacaggtttg aggacgatgg tgaactcaat 240 ctggtctacg aaaacctg 258 <210> SEQ ID NO 130 <211> LENGTH: 540 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-BAFFR-tMyD88 CER87 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 130 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Trp Arg Arg 270 275 280 Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly 285 290 295 Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro 300 305 310 Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp 315 320 325 330 Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val Pro Ala Thr Glu 335 340 345 Leu Gly Ser Thr Glu Leu Val Thr Thr Lys Thr Ala Gly Pro Glu Gln 350 355 360 Gln Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser 365 370 375 Ser Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg 380 385 390 Arg Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp 395 400 405 410 Thr Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln 415 420 425 Leu Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln 430 435 440 Gly Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys 445 450 455 Leu Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu 460 465 470 Asp Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys 475 480 485 490 Pro Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu 495 500 505 Leu Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly 510 515 <210> SEQ ID NO 131 <211> LENGTH: 507 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-DAP12-tMyD88 CER88 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 131 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Tyr Phe Leu Gly 270 275 280 Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys 285 290 295 Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln 300 305 310 Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 315 320 325 330 Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser 335 340 345 Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg 350 355 360 Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr 365 370 375 Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu 380 385 390 Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly 395 400 405 410 Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu 415 420 425 Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp 430 435 440 Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro 445 450 455 Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu 460 465 470 Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly 475 480 485 <210> SEQ ID NO 132 <211> LENGTH: 53 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated NFAM1 signaling domain <400> SEQUENCE: 132 Leu Trp Asn Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg 1 5 10 15 Lys Cys Pro Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser 20 25 30 Glu Ser Val Tyr Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala 35 40 45 Cys Ile Glu Asn Glu 50 <210> SEQ ID NO 133 <211> LENGTH: 931 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TIM4-MERTK-tMYD88 CER92 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 133 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Met Ala Ala Gly Gly Pro Gly Ala 750 755 760 Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu Pro Leu Ala Ala 765 770 775 Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe Leu Asn Val Arg 780 785 790 Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu Glu Met Asp Phe 795 800 805 810 Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala Asp Pro Thr Gly 815 820 825 Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala Ser Val Gly Arg 830 835 840 Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp Val Leu Leu Glu 845 850 855 Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr Ile Leu Lys Gln 860 865 870 Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala Ala Val Asp Ser 875 880 885 890 Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr Thr Leu Asp Asp 895 900 905 Pro Leu Gly <210> SEQ ID NO 134 <211> LENGTH: 828 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TIM4-MERTK-DAP12 CER94 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 134 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Tyr Phe Leu Gly Arg Leu Val Pro 750 755 760 Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr 765 770 775 Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val 780 785 790 Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 795 800 805 <210> SEQ ID NO 135 <211> LENGTH: 2754 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 binding domain <400> SEQUENCE: 135 gccgccggag cagacgcggg gcccgggccc gagccgtgcg ccacgctggt gcagggaaag 60 ttcttcggct acttctccgc ggccgccgtg ttcccggcca acgcctcgcg ctgctcctgg 120 acgctacgca acccggaccc gcggcgctac actctctaca tgaaggtggc caaggcgccc 180 gtgccctgca gcggccccgg ccgcgtgcgc acctaccagt tcgactcctt cctcgagtcc 240 acgcgcacct acctgggcgt ggagagcttc gacgaggtgc tgcggctctg cgacccctcc 300 gcacccctgg ccttcctgca ggccagcaag cagttcctgc agatgcggcg ccagcagccg 360 ccccagcacg acgggctccg gccccgggcc gggccgccgg gccccaccga cgacttctcc 420 gtggagtacc tggtggtggg gaaccgcaac cccagccgtg ccgcctgcca gatgctgtgc 480 cgctggctgg acgcgtgtct ggccggtagt cgcagctcgc acccctgcgg gatcatgcag 540 accccctgcg cctgcctggg cggcgaggcg ggcggccctg ccgcgggacc cctggccccc 600 cgcggggatg tctgcttgag agatgcggtg gctggtggcc ctgaaaactg cctcaccagc 660 ctgacccagg accggggcgg gcacggcgcc acaggcggct ggaagctgtg gtccctgtgg 720 ggcgaatgca cgcgggactg cgggggaggc ctccagacgc ggacgcgcac ctgcctgccc 780 gcgccgggcg tggagggcgg cggctgcgag ggggtgctgg aggagggtcg ccagtgcaac 840 cgcgaggcct gcggccccgc tgggcgcacc agctcccgga gccagtccct gcggtccaca 900 gatgcccggc ggcgcgagga gctgggggac gagctgcagc agtttgggtt cccagccccc 960 cagaccggtg acccagcagc cgaggagtgg tccccgtgga gcgtgtgctc cagcacctgc 1020 ggcgagggct ggcagacccg cacgcgcttc tgcgtgtcct cctcctacag cacgcagtgc 1080 agcggacccc tgcgcgagca gcggctgtgc aacaactctg ccgtgtgccc agtgcatggt 1140 gcctgggatg agtggtcgcc ctggagcctc tgctccagca cctgtggccg tggctttcgg 1200 gatcgcacgc gcacctgcag gcccccccag tttgggggca acccctgtga gggccctgag 1260 aagcaaacca agttctgcaa cattgccctg tgccctggcc gggcagtgga tggaaactgg 1320 aatgagtggt cgagctggag cgcctgctcc gccagctgct cccagggccg acagcagcgc 1380 acgcgtgaat gcaacgggcc ttcctacggg ggtgcggagt gccagggcca ctgggtggag 1440 acccgagact gcttcctgca gcagtgccca gtggatggca agtggcaggc ctgggcgtca 1500 tggggcagtt gcagcgtcac gtgtggggct ggcagccagc gacgggagcg tgtctgctct 1560 gggcccttct tcgggggagc agcctgccag ggcccccagg atgagtaccg gcagtgcggc 1620 acccagcggt gtcccgagcc ccatgagatc tgtgatgagg acaactttgg tgctgtgatc 1680 tggaaggaga ccccagcggg agaggtggct gctgtccggt gtccccgcaa cgccacagga 1740 ctcatcctgc gacggtgtga gctggacgag gaaggcatcg cctactggga gccccccacc 1800 tacatccgct gtgtttccat tgactacaga aacatccaga tgatgacccg ggagcacctg 1860 gccaaggctc agcgagggct gcctggggag ggggtctcgg aggtcatcca gacactggtg 1920 gagatctctc aggacgggac cagctacagt ggggacctgc tgtccaccat cgatgtcctg 1980 aggaacatga cagagatttt ccggagagcg tactacagcc ccacccctgg ggacgtacag 2040 aactttgtcc agatccttag caacctgttg gcagaggaga atcgggacaa gtgggaggag 2100 gcccagctgg cgggccccaa cgccaaggag ctgttccggc tggtggagga ctttgtggac 2160 gtcatcggct tccgcatgaa ggacctgagg gatgcatacc aggtgacaga caacctggtt 2220 ctcagcatcc ataagctccc agccagcgga gccactgaca tcagcttccc catgaagggc 2280 tggcgggcca cgggtgactg ggccaaggtg ccagaggaca gggtcactgt gtccaagagt 2340 gtcttctcca cggggctgac agaggccgat gaagcatccg tgtttgtggt gggcaccgtg 2400 ctctacagga acctgggcag cttcctggcc ctgcagagga acacgaccgt cctgaattct 2460 aaggtgatct ccgtgactgt gaaacccccg cctcgctccc tgcgcacacc cttggagatc 2520 gagtttgccc acatgtataa tggcaccacc aaccagacct gtatcctgtg ggatgagacg 2580 gatgtaccct cctcctccgc ccccccgcag ctcgggccct ggtcgtggcg cggctgccgc 2640 acggtgcccc tcgacgccct ccggacgcgc tgcctctgtg accggctctc caccttcgcc 2700 atcttagccc agctcagcgc cgacgcgaac atggagaagg cgactctgcc gtcg 2754 <210> SEQ ID NO 136 <211> LENGTH: 397 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 signaling domain <400> SEQUENCE: 136 Arg Arg Glu Val Gln Asp Ala Val Lys Cys Arg Val Val Asp Arg Gln 1 5 10 15 Glu Glu Gly Asn Gly Asp Ser Gly Gly Ser Phe Gln Asn Gly His Ala 20 25 30 Gln Leu Met Thr Asp Phe Glu Lys Asp Val Asp Leu Ala Cys Arg Ser 35 40 45 Val Leu Asn Lys Asp Ile Ala Ala Cys Arg Thr Ala Thr Ile Thr Gly 50 55 60 Thr Leu Lys Arg Pro Ser Leu Pro Glu Glu Glu Lys Leu Lys Leu Ala 65 70 75 80 His Ala Lys Gly Pro Pro Thr Asn Phe Asn Ser Leu Pro Ala Asn Val 85 90 95 Ser Lys Leu His Leu His Gly Ser Pro Arg Tyr Pro Gly Gly Pro Leu 100 105 110 Pro Asp Phe Pro Asn His Ser Leu Thr Leu Lys Arg Asp Lys Ala Pro 115 120 125 Lys Ser Ser Phe Val Gly Asp Gly Asp Ile Phe Lys Lys Leu Asp Ser 130 135 140 Glu Leu Ser Arg Ala Gln Glu Lys Ala Leu Asp Thr Ser Tyr Val Ile 145 150 155 160 Leu Pro Thr Ala Thr Ala Thr Leu Arg Pro Lys Pro Lys Glu Glu Pro 165 170 175 Lys Tyr Ser Ile His Ile Asp Gln Met Pro Gln Thr Arg Leu Ile His 180 185 190 Leu Ser Thr Ala Pro Glu Ala Ser Leu Pro Ala Arg Ser Pro Pro Ser 195 200 205 Arg Gln Pro Pro Ser Gly Gly Pro Pro Glu Ala Pro Pro Ala Gln Pro 210 215 220 Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Gln Gln Pro Leu Pro 225 230 235 240 Pro Pro Pro Asn Leu Glu Pro Ala Pro Pro Ser Leu Gly Asp Pro Gly 245 250 255 Glu Pro Ala Ala His Pro Gly Pro Ser Thr Gly Pro Ser Thr Lys Asn 260 265 270 Glu Asn Val Ala Thr Leu Ser Val Ser Ser Leu Glu Arg Arg Lys Ser 275 280 285 Arg Tyr Ala Glu Leu Asp Phe Glu Lys Ile Met His Thr Arg Lys Arg 290 295 300 His Gln Asp Met Phe Gln Asp Leu Asn Arg Lys Leu Gln His Ala Ala 305 310 315 320 Glu Lys Asp Lys Glu Val Leu Gly Pro Asp Ser Lys Pro Glu Lys Gln 325 330 335 Gln Thr Pro Asn Lys Arg Pro Trp Glu Ser Leu Arg Lys Ala His Gly 340 345 350 Thr Pro Thr Trp Val Lys Lys Glu Leu Glu Pro Leu Gln Pro Ser Pro 355 360 365 Leu Glu Leu Arg Ser Val Glu Trp Glu Arg Ser Gly Ala Thr Ile Pro 370 375 380 Leu Val Gly Gln Asp Ile Ile Asp Leu Gln Thr Glu Val 385 390 395 <210> SEQ ID NO 137 <211> LENGTH: 171 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 137 aagctgcttg tcaccatcca cgaccggagg gagtttgcaa agtttcagag cgagcgatcc 60 agggcccgct atgaaatggc ttcaaatcca ttatacagaa agcctatctc cacgcacact 120 gtggacttca ccttcaacaa gttcaacaaa tcctacaatg gcactgtgga c 171 <210> SEQ ID NO 138 <211> LENGTH: 1419 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 138 aaaagagtcc aggagacaaa gtttgggaat gcattcacag aggaggattc tgaattagtg 60 gtgaattata tagcaaagaa atccttctgt cggcgagcca ttgaacttac cttacatagc 120 ttgggagtca gtgaggaact acaaaataaa ctagaagatg ttgtgattga caggaatctt 180 ctaattcttg gaaaaattct gggtgaagga gagtttgggt ctgtaatgga aggaaatctt 240 aagcaggaag atgggacctc tctgaaagtg gcagtgaaga ccatgaagtt ggacaactct 300 tcacagcggg agatcgagga gtttctcagt gaggcagcgt gcatgaaaga cttcagccac 360 ccaaatgtca ttcgacttct aggtgtgtgt atagaaatga gctctcaagg catcccaaag 420 cccatggtaa ttttaccctt catgaaatac ggggacctgc atacttactt actttattcc 480 cgattggaga caggaccaaa gcatattcct ctgcagacac tattgaagtt catggtggat 540 attgccctgg gaatggagta tctgagcaac aggaattttc ttcatcgaga tttagctgct 600 cgaaactgca tgttgcgaga tgacatgact gtctgtgttg cggacttcgg cctctctaag 660 aagatttaca gtggcgatta ttaccgccaa ggccgcattg ctaagatgcc tgttaaatgg 720 atcgccatag aaagtcttgc agaccgagtc tacacaagta aaagtgatgt gtgggcattt 780 ggcgtgacca tgtgggaaat agctacgcgg ggaatgactc cctatcctgg ggtccagaac 840 catgagatgt atgactatct tctccatggc cacaggttga agcagcccga agactgcctg 900 gatgaactgt atgaaataat gtactcttgc tggagaaccg atcccttaga ccgccccacc 960 ttttcagtat tgaggctgca gctagaaaaa ctcttagaaa gtttgcctga cgttcggaac 1020 caagcagacg ttatttacgt caatacacag ttgctggaga gctctgaggg cctggcccag 1080 ggctccaccc ttgctccact ggacttgaac atcgaccctg actctataat tgcctcctgc 1140 actccccgcg ctgccatcag tgtggtcaca gcagaagttc atgacagcaa acctcatgaa 1200 ggacggtaca tcctgaatgg gggcagtgag gaatgggaag atctgacttc tgccccctct 1260 gctgcagtca cagctgaaaa gaacagtgtt ttaccggggg agagacttgt taggaatggg 1320 gtctcctggt cccattcgag catgctgccc ttgggaagct cattgcccga tgaacttttg 1380 tttgctgacg actcctcaga aggctcagaa gtcctgatg 1419 <210> SEQ ID NO 139 <211> LENGTH: 1191 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 signaling domain <400> SEQUENCE: 139 cgtagagagg tccaggacgc tgtgaaatgc cgtgtggttg accggcagga ggagggcaac 60 ggggactcag ggggctcctt ccagaacggc cacgcccagc tcatgaccga cttcgagaag 120 gacgtggatc tggcctgtag atcagtgctg aacaaggaca tcgcggcctg ccgcactgcc 180 accatcacgg gcacactgaa gcggccgtct ctgcccgagg aggagaagct gaagctggcc 240 catgccaagg ggccgcccac caatttcaac agcctgccgg ccaacgtgtc caagctgcac 300 ctgcacggct caccccgcta tcccggcggg cccctgcccg acttccccaa ccactcactg 360 accctcaaga gggacaaggc gcccaagtcc tccttcgtcg gtgacgggga catcttcaag 420 aagctggact cggagctgag ccgggcccag gagaaggctc tggacacgag ctacgtgatc 480 ctgcccacgg ccacggccac gctgcggccc aagcccaagg aggagcccaa gtacagcatc 540 cacattgacc agatgccgca gacccgcctc atccacctca gcacggcccc cgaggccagc 600 ctccccgccc gcagcccgcc ctcccgccag ccccccagcg gcgggccccc cgaggcaccc 660 cctgcccagc ccccaccgcc tccgccccca ccgccaccac ctccccagca gcccctgccc 720 ccaccgccca atctggagcc ggcacccccc agcctggggg atcccgggga gcctgccgcc 780 catccgggac ccagcacggg gcccagcacc aagaacgaga atgtcgccac cttgtctgtg 840 agctccctgg agcggcggaa gtcgcggtat gcagaactgg actttgagaa gatcatgcac 900 acccggaagc ggcaccaaga catgttccag gacctgaacc ggaagctgca gcacgcagcg 960 gagaaggaca aggaggtgct ggggccggac agcaagccgg aaaagcagca gacgcccaac 1020 aagaggccct gggagagcct ccggaaagcc cacgggacgc ccacgtgggt gaagaaggag 1080 ctggagccgc tgcagccgtc gccgctggag cttcgcagcg tggagtggga gaggtcgggc 1140 gccacgatcc cgctggtggg ccaggacatc atcgacctcc agaccgaggt c 1191 <210> SEQ ID NO 140 <211> LENGTH: 1191 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ELMO <400> SEQUENCE: 140 cgtagagagg tccaggacgc tgtgaaatgc cgtgtggttg accggcagga ggagggcaac 60 ggggactcag ggggctcctt ccagaacggc cacgcccagc tcatgaccga cttcgagaag 120 gacgtggatc tggcctgtag atcagtgctg aacaaggaca tcgcggcctg ccgcactgcc 180 accatcacgg gcacactgaa gcggccgtct ctgcccgagg aggagaagct gaagctggcc 240 catgccaagg ggccgcccac caatttcaac agcctgccgg ccaacgtgtc caagctgcac 300 ctgcacggct caccccgcta tcccggcggg cccctgcccg acttccccaa ccactcactg 360 accctcaaga gggacaaggc gcccaagtcc tccttcgtcg gtgacgggga catcttcaag 420 aagctggact cggagctgag ccgggcccag gagaaggctc tggacacgag ctacgtgatc 480 ctgcccacgg ccacggccac gctgcggccc aagcccaagg aggagcccaa gtacagcatc 540 cacattgacc agatgccgca gacccgcctc atccacctca gcacggcccc cgaggccagc 600 ctccccgccc gcagcccgcc ctcccgccag ccccccagcg gcgggccccc cgaggcaccc 660 cctgcccagc ccccaccgcc tccgccccca ccgccaccac ctccccagca gcccctgccc 720 ccaccgccca atctggagcc ggcacccccc agcctggggg atcccgggga gcctgccgcc 780 catccgggac ccagcacggg gcccagcacc aagaacgaga atgtcgccac cttgtctgtg 840 agctccctgg agcggcggaa gtcgcggtat gcagaactgg actttgagaa gatcatgcac 900 acccggaagc ggcaccaaga catgttccag gacctgaacc ggaagctgca gcacgcagcg 960 gagaaggaca aggaggtgct ggggccggac agcaagccgg aaaagcagca gacgcccaac 1020 aagaggccct gggagagcct ccggaaagcc cacgggacgc ccacgtgggt gaagaaggag 1080 ctggagccgc tgcagccgtc gccgctggag cttcgcagcg tggagtggga gaggtcgggc 1140 gccacgatcc cgctggtggg ccaggacatc atcgacctcc agaccgaggt c 1191 <210> SEQ ID NO 141 <211> LENGTH: 126 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Fc(epsilon) RI(gamma) signaling domain <400> SEQUENCE: 141 cgactgaaga tccaagtgcg aaaggcagct ataaccagct atgagaaatc agatggtgtt 60 tacacgggcc tgagcaccag gaaccaggag acttacgaga ctctgaagca tgagaaacca 120 ccacag 126 <210> SEQ ID NO 142 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 transmembrane domain <400> SEQUENCE: 142 Val Thr Leu Ile Val Gly Cys Gly Val Ser Ser Leu Thr Leu Leu Met 1 5 10 15 Leu Val Ile Ile Tyr 20 <210> SEQ ID NO 143 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 transmembrane domain <400> SEQUENCE: 143 gtgacgctca tcgtgggctg tggcgtgtcc tctctcaccc tgctcatgct ggtcatcatc 60 tac 63 <210> SEQ ID NO 144 <211> LENGTH: 81 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD28 transmembrane domain <400> SEQUENCE: 144 ttttgggtgc tggtggtggt tggtggagtc ctggcttgct atagcttgct agtaacagtg 60 gcctttatta ttttctgggt g 81 <210> SEQ ID NO 145 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: DAP12 transmembrane domain <400> SEQUENCE: 145 ggcgtgctgg cagggatcgt gatgggagac ctggtgctga cagtgctcat tgccctggcc 60 gtg 63 <210> SEQ ID NO 146 <400> SEQUENCE: 146 000 <210> SEQ ID NO 147 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: T2A self-cleaving peptide <400> SEQUENCE: 147 Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro 1 5 10 15 Gly Pro <210> SEQ ID NO 148 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: E2A self-cleaving peptide <400> SEQUENCE: 148 Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 1 5 10 15 Asn Pro Gly Pro 20 <210> SEQ ID NO 149 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: F2A self-cleaving peptide <400> SEQUENCE: 149 Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val 1 5 10 15 Glu Ser Asn Pro Gly Pro 20 <210> SEQ ID NO 150 <400> SEQUENCE: 150 000 <210> SEQ ID NO 151 <400> SEQUENCE: 151 000 <210> SEQ ID NO 152 <211> LENGTH: 774 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CER97 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 152 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys 270 275 280 Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly 285 290 295 Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr 300 305 310 Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu 315 320 325 330 Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys 335 340 345 Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn 350 355 360 Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala 365 370 375 Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys 380 385 390 Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys 395 400 405 410 Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu 415 420 425 Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe 445 450 455 Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe 460 465 470 Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met 475 480 485 490 Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr 540 545 550 Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln 555 560 565 570 Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala 575 580 585 Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe 590 595 600 Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro 605 610 615 Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met Asp Glu Gly Gly 620 625 630 Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr 635 640 645 650 Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val 655 660 665 His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro 670 675 680 Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp 685 690 695 Gly Ala Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala 700 705 710 Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr 715 720 725 730 Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr 735 740 745 Gln Arg Pro Tyr Tyr Lys 750 <210> SEQ ID NO 153 <211> LENGTH: 767 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CER98 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 153 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys 270 275 280 Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly 285 290 295 Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr 300 305 310 Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu 315 320 325 330 Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys 335 340 345 Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn 350 355 360 Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala 365 370 375 Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys 380 385 390 Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys 395 400 405 410 Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu 415 420 425 Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe 445 450 455 Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe 460 465 470 Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met 475 480 485 490 Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr 540 545 550 Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln 555 560 565 570 Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala 575 580 585 Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe 590 595 600 Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro 605 610 615 Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met Asp Glu Gly Gly 620 625 630 Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr 635 640 645 650 Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val 655 660 665 His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro 670 675 680 Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp 685 690 695 Gly Ala Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly 700 705 710 Leu Asp Ile Asp Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu Arg 715 720 725 730 Thr Gly Glu Val Lys Trp Ser Val Gly Glu His Pro Gly Gln Glu 735 740 745

1 SEQUENCE LISTING <160> NUMBER OF SEQ ID NOS: 153 <210> SEQ ID NO 1 <211> LENGTH: 870 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 binding domain <400> SEQUENCE: 1 atgcaccccc aggttgttat actttcattg atcctgcatt tggccgactc cgtggcgggt 60 tccgtaaaag ttggagggga agctggacca agcgtcacct tgccttgcca ctactctgga 120 gccgtgacga gtatgtgctg gaatcgagga tcctgtagtc ttttcacatg ccaaaatggc 180 atagtttgga ccaatgggac gcacgtcacc taccgaaaag acactagata caaactcctg 240 ggtgacctca gcaggagaga tgtgtctctg actattgaaa acactgctgt ttctgactct 300 ggagtctact gttgccgggt cgagcaccga ggatggttca atgacatgaa gatcacggtc 360 agcttggaaa tcgtcccgcc caaggtaacc actacaccaa tagttactac ggttcccacg 420 gtaaccacgg ttcgaaccag caccacagta cccacaacta cgaccgttcc aaccactaca 480 gtccccacaa ccatgagtat ccctacgaca actacggtcc tgacaaccat gaccgtcagc 540 actaccacga gtgtgcctac gactactagc ataccgacga ctacttcagt tccagtcacc 600 accacggtga gtacattcgt gcctccaatg ccattgccga ggcaaaacca cgaacccgtg 660 gcgacatctc cgtctagtcc gcaaccagca gagacccatc ccaccacgct tcagggggca 720 atcaggagag aacctacaag ttcacccctc tacagctata caaccgatgg aaacgacaca 780 gttacagaaa gtagtgacgg tttgtggaat aacaaccaaa cacaattgtt cctggagcac 840 agtctgttga cagccaacac tacaaaggga 870 <210> SEQ ID NO 2 <211> LENGTH: 942 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain <400> SEQUENCE: 2 atgagtaaag agccgcttat cctgtggctt atgatagagt tttggtggtt gtatttgacc 60 ccggtcacga gcgaaacggt agtgactgaa gtattgggtc atcgggtaac cttgccttgc 120 ttgtatagct cctggtctca taatagtaat agcatgtgct ggggcaagga ccaatgcccc 180 tatagcggat gcaaggaggc gctcattcgc acagacggaa tgcgggtgac atcaaggaag 240 agtgctaagt accggcttca gggcacaatc ccacgcggcg acgtgtcact gactatcctt 300 aatccatccg agagcgactc tggtgtctat tgttgcagga tcgaggttcc gggatggttc 360 aatgatgtaa agatcaatgt aagactcaat ctgcaacggg catctacaac cacgcatcgg 420 acagccacta ctaccacaag gagaacaact actacgtcac ccacgactac tcgacagatg 480 accactacac ctgcggccct gccaactacg gttgtaacta ctccggatct gacaaccggg 540 acaccgttgc aaatgacaac cattgcagta tttaccacgg caaacacgtg tctctctctg 600 accccatcta ctcttccgga ggaggccacc gggctcctta caccggagcc gtctaaggaa 660 ggcccaatct tgaccgcaga gagtgagacc gtacttccga gcgattcatg gtccagtgtc 720 gagagcacat ccgctgacac cgtccttctt acgtccaaag aaagtaaagt ttgggacctc 780 ccgtccacga gccacgtttc tatgtggaag acctcagata gcgttagctc cccacagcca 840 ggagcaagcg acaccgcagt accggagcaa aacaagacga ctaagactgg ccagatggat 900 ggtatcccaa tgtcaatgaa aaatgagatg cccatatcac aa 942 <210> SEQ ID NO 3 <211> LENGTH: 483 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FA58C2 binding domain <400> SEQUENCE: 3 ctcaacgggt gtgctaatcc ccttggcctg aagaataaca gcatacctga caagcaaata 60 acagcgtcaa gttcttataa aacttggggg ctgcatctgt tctcctggaa ccccagttac 120 gctagactcg acaaacaagg caattttaac gcatgggtgg caggctctta cgggaacgat 180 cagtggctgc aagtagactt gggaagtagt aaggaggtga ctgggatcat tacccagggg 240 gcacgaaatt tcggttccgt tcagttcgtt gcatcttata aggtagcgta ttcaaatgac 300 tccgcgaatt ggaccgaata tcaggacccg cgaaccggat caagcaagat ttttccgggg 360 aattgggaca accactctca caaaaaaaat ttgtttgaaa cacctatact ggcgcggtac 420 gttagaatcc tcccagttgc ctggcacaac cggatagcgc ttagactgga attgttgggg 480 tgc 483 <210> SEQ ID NO 4 <211> LENGTH: 876 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI binding domain <400> SEQUENCE: 4 atgtggttcc tgactacgtt gttgctgtgg gtccctgtag acggccaagt agacacaacg 60 aaagcagtga tcacgctcca accgccttgg gtgtctgtgt tccaagaaga aacagttaca 120 ctgcactgtg aggtcctcca cctgcctggt tcttcatcta ctcaatggtt tctcaacgga 180 acagcaacac aaacaagtac cccttcctac agaattacga gtgcatctgt taacgattca 240 ggagagtata ggtgccagcg agggctttca ggccggtccg accccattca actcgaaatt 300 caccgcggtt ggcttctgct gcaagtatcc tctcgggtct tcacggaagg tgaaccactt 360 gccttgcgct gtcacgcatg gaaagataag ctcgtctaca acgttttgta ttatcggaat 420 ggaaaggcat ttaagttttt tcattggaac tcaaacctta cgatcctcaa aaccaatatc 480 agtcataacg gtacgtacca ctgctcaggc atgggcaagc atcgctatac gtccgcaggg 540 attagcgtga cagttaagga gctcttcccc gcgcctgtgc tgaatgcgag cgtaacttca 600 ccccttctgg agggcaactt ggtgaccctc tcttgtgaga cgaaacttct ccttcagagg 660 ccgggcctgc aactctattt cagcttttat atgggttcta aaactcttcg aggcagaaac 720 acgagcagcg aatatcagat actgactgcc cggcgggaag acagtggcct ttattggtgc 780 gaggctgcaa cagaagatgg caatgtcctt aaaaggtctc ccgaattgga gctccaagtg 840 cttggcttgc aactccctac acccgtatgg ttccac 876 <210> SEQ ID NO 5 <211> LENGTH: 282 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: GAS6 binding domain <400> SEQUENCE: 5 atggctccct ctttgtcacc aggacctgcg gctcttaggc gagccccgca gctgctgctt 60 ctcctgctcg ctgcagaatg cgctctcgct gcactcttgc ccgcgaggga ggcgactcag 120 ttcttgcgcc cccggcagag acgagcattc caagtctttg aggaagcgaa acaaggtcat 180 ctcgagcgag aatgcgtgga ggagctgtgt tctagggagg aagcacgcga agtctttgag 240 aatgacccgg aaacggacta cttttacccc cggtatcttg at 282 <210> SEQ ID NO 6 <211> LENGTH: 261 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Protein S binding domain <400> SEQUENCE: 6 atgcgcgtgt tggggggtcg ctgtggtgcg ctccttgctt gtctcctttt ggttcttccc 60 gtctccgagg ctaatttcct gtcaaaacaa caggctagtc aagtcttggt gcgcaagagg 120 agagctaaca gccttctgga agagaccaag caaggtaatc tggagagaga gtgtatcgag 180 gaactttgta acaaagagga agcacgcgaa gtatttgaaa atgacccgga aaccgattat 240 ttttacccaa aatatctcgt a 261 <210> SEQ ID NO 7 <211> LENGTH: 606 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim3 binding domain <400> SEQUENCE: 7 atgtttagcc atctcccttt tgattgcgtc ttgttgcttc ttcttctcct tctgacgaga 60 tcatctgaag ttgaatatcg cgcggaagtc ggccaaaacg catatctgcc gtgtttttac 120 accccggctg caccggggaa cttggttccc gtttgttggg gtaagggggc gtgtcccgtt 180 tttgagtgcg gtaacgtagt gctccgaact gatgaaagag atgtaaatta ctggacgagc 240 cggtactggt tgaatgggga ttttaggaag ggcgacgttt cccttaccat agaaaacgta 300 actcttgcgg attctgggat ttattgttgc aggatacaaa tccccggaat aatgaacgat 360 gagaaattca atttgaagct cgtaataaaa ccggcaaaag taactccagc tcccaccagg 420 cagcgagatt ttacggcagc atttcccagg atgctcacta ctcgcggtca tggccctgcc 480 gagactcaga ccctcggtag tcttcctgat atcaatctca cgcaaattag tacattggcg 540 aatgaattga gggattcaag actcgccaat gatctgcgcg acagtggagc gactattagg 600 ataggg 606 <210> SEQ ID NO 8 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 transmembrane domain <400> SEQUENCE: 8 atatacgctg gagtctgtat aagtgtcctt gtactgttgg cgttgctggg ggtcattatt 60 gcc 63 <210> SEQ ID NO 9 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 transmembrane domain <400> SEQUENCE: 9

ttgcttatga ttattgcgcc aagccttgga tttgtgctgt tcgcactctt cgtagctttt 60 ctc 63 <210> SEQ ID NO 10 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI transmembrane domain <400> SEQUENCE: 10 gtactgtttt atctcgccgt agggataatg ttcctcgtga acaccgtact gtgggtaaca 60 ata 63 <210> SEQ ID NO 11 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD8a transmembrane domain <400> SEQUENCE: 11 atatacattt gggcaccgct ggctggaact tgcggcgttc tcttgttgag tctggtgatt 60 act 63 <210> SEQ ID NO 12 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK transmembrane domain <400> SEQUENCE: 12 tttggctgtt tctgtggatt tattctgatt ggtcttatcc tctatatttc cttggcgatc 60 aga 63 <210> SEQ ID NO 13 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl transmembrane domain <400> SEQUENCE: 13 tatgtcttgc ttggtgccgt cgttgctgcc gcctgtgtgt tgatactcgc acttttcttg 60 gtg 63 <210> SEQ ID NO 14 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 transmembrane domain <400> SEQUENCE: 14 gtacccgtcg ttttgggggt cctgaccgcg ctcgttactg cggcagcact cgcactgata 60 ctt 63 <210> SEQ ID NO 15 <211> LENGTH: 66 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD4 transmembrane domain <400> SEQUENCE: 15 atggctctga tcgtactggg cggagtggca ggattgctgc tctttattgg actgggcatt 60 ttcttc 66 <210> SEQ ID NO 16 <211> LENGTH: 1428 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 16 gcgctgcggc gaagggtaca ggagacgaaa ttcgggggag cctttagtga agaagacagc 60 cagttggtgg taaattacag agcgaaaaaa tctttctgcc gacgcgctat tgagcttact 120 cttcaaagcc tcggtgtaag tgaggagttg cagaataaat tggaggacgt agtcatcgac 180 cgcaaccttc tggtcctcgg aaaagtcctc ggagaaggtg aattcggctc agtaatggaa 240 ggcaatctca aacaagaaga cggaacttct cagaaggtag cagtaaaaac catgaaactc 300 gacaacttca gccagcggga aatcgaagaa ttcctgtccg aagccgcctg tatgaaagac 360 ttcaatcacc caaacgtgat aagacttctc ggcgtatgta tagagttgtc ttcccagggc 420 atccccaaac caatggtgat actcccattt atgaagtacg gggacttgca cacattcctg 480 ttgtattcca gacttaatac aggacccaag tatatacatt tgcagaccct gctcaaattt 540 atgatggaca tcgcgcaggg gatggagtat ctcagcaaca ggaatttttt gcatcgcgac 600 cttgctgcca ggaactgtat gttgagggac gacatgacgg tgtgtgtagc cgacttcggt 660 cttagcaaga agatctattc tggagactat tacaggcaag gcagaatagc taagatgccg 720 gtcaagtgga tcgctattga gagcctcgca gaccgggtct atacttcaaa gtcagacgtt 780 tgggcttttg gggtaaccat gtgggagatc actacgaggg ggatgacgcc ctatcccggg 840 gtccaaaatc acgagatgta tgattatctc ttgcatggcc accggctgaa acagcctgag 900 gactgtctgg acgagctcta cgatattatg tattcttgtt ggtccgcgga ccccctcgat 960 agaccaacct tttctgttct tcgactgcag ctcgaaaagc tttccgaatc tttgcctgat 1020 gcacaggaca aagaaagcat catttatata aatacacagc tcctggaatc ttgcgaagga 1080 attgctaatg gacctagtct gactggattg gacatgaata ttgacccgga cagcataatt 1140 gcatcttgca cacctggtgc agcggtatca gtcgtgacgg ccgaggtcca tgaaaacaat 1200 ctgcgggagg agcggtacat tttgaacggc ggaaacgaag agtgggagga cgtcagctca 1260 accccctttg cagccgtgac gccagagaaa gacggggtac ttcctgagga ccgccttacc 1320 aagaacgggg tatcctggtc tcaccacagc accctcccac ttgggagtcc atctcccgac 1380 gagcttctct tcgtagatga ttcacttgaa gattcagagg tgctcatg 1428 <210> SEQ ID NO 17 <211> LENGTH: 1266 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl signaling domain <400> SEQUENCE: 17 caccggagaa aaaaagagac ccgctacgga gaggtctttg agcctacggt cgagagaggt 60 gagcttgttg tccggtacag agtgaggaag agctattcac ggaggactac tgaagccacc 120 ctgaattcac tcggcatcag cgaagagctg aaagagaaac ttcgggacgt aatggtcgat 180 cggcacaagg tagccctcgg gaagacgttg ggagagggcg aatttggggc cgtcatggag 240 ggtcagttga accaagatga ctcaatactt aaagtagcag tcaaaacgat gaaaatcgca 300 atttgtactc gctcagagct cgaagacttt ctctctgagg cggtatgcat gaaggaattc 360 gaccacccaa atgtaatgcg attgatcggt gtctgcttcc aaggttccga aagagagtca 420 tttcctgcac ccgttgtcat tttgccattt atgaagcatg gggacctcca ctcatttctc 480 ctctattcta gattgggtga ccaaccggtt tacctcccga cccaaatgct cgttaagttc 540 atggccgaca ttgcttccgg gatggagtac ctgagtacca agcggtttat acatcgggat 600 ctcgcagcac gaaactgcat gttgaatgag aacatgtctg tctgtgtggc tgactttgga 660 ctctccaaaa aaatttacaa cggtgattat taccgccagg gaagaatcgc taagatgccc 720 gtgaagtgga tagctattga gtcactcgct gatcgcgtat acactagtaa gtccgacgta 780 tggtcctttg gtgtcacaat gtgggagatt gcgaccaggg ggcagacacc atatcccggc 840 gtggagaact ccgagattta tgattatctg cgacagggta acagacttaa gcaacctgcc 900 gattgcttgg atgggctcta cgctctgatg tctagatgct gggaattgaa tcctcaagat 960 cggccaagct tcactgaact gagagaagac ctggaaaata ccctgaaagc gctcccgccg 1020 gcgcaagaac cagatgaaat cttgtacgtc aatatggacg aagggggagg ctaccctgaa 1080 ccccctgggg cggccggtgg ggcggacccc ccgacacaac cagatccgaa agactcctgt 1140 tcttgtctta ccgctgctga ggtacatccg gcaggaagat atgttttgtg tccctctacg 1200 acaccctctc ccgcacagcc cgcggatcgc gggtcacccg cggctccagg acaagaagat 1260 ggggca 1266 <210> SEQ ID NO 18 <211> LENGTH: 1320 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 signaling domain <400> SEQUENCE: 18 ttgcggaagc ggcgaaagga aaccagattc ggtcaagctt tcgacagcgt aatggcccgg 60 ggtgagccag ccgtccactt tagagccgct cggagcttca atagggaacg accggagaga 120 atcgaggcta ctctcgattc tctcggaata tctgacgagt tgaaagaaaa actggaggat 180 gtcctcatcc cagaacaaca atttaccctc ggccgaatgc ttggaaaggg tgagtttggg 240 tcagttcgcg aggcgcagct taaacaggaa gacggtagtt ttgttaaagt cgcagtaaaa 300 atgttgaagg cggacataat cgcatccagc gatattgagg aatttcttcg cgaagcggca 360 tgtatgaaag agttcgacca cccgcacgtt gccaagctcg tgggcgtgtc tcttcgaagc 420 cgagctaagg gtagactccc tatcccaatg gtaatacttc cttttatgaa acatggggac 480 ttgcacgctt ttctgctcgc ttccaggata ggagaaaatc cgtttaattt gccgctccaa 540 acgcttatca ggtttatggt tgatattgcg tgtgggatgg aatacttgag ttcacgcaat 600 ttcatccatc gagacctggc cgcgcgaaat tgtatgctcg cagaggatat gaccgtatgt 660 gtagctgatt tcggcttgtc acgcaagata tatagcggcg attattatag acagggttgt 720 gcctctaagc tccctgtaaa gtggttggca ttggaatcac tggcggataa cctctatact 780 gtccagtcag atgtgtgggc atttggtgtc actatgtggg agattatgac acggggtcag 840 acaccctacg caggaatcga gaacgcggag atatataact acctgatagg tggcaaccga 900 ctgaaacaac ctccggaatg catggaggac gtgtatgacc tcatgtacca gtgttggagt 960 gccgatccga aacaaagacc tagtttcact tgcctgagaa tggagttgga gaatattttg 1020 ggtcagttgt ccgtactgag cgccagccaa gatccgttgt atataaatat agagcgggcg 1080 gaggagccca cggccggcgg gtccctggaa cttcctggac gagaccaacc gtactcaggg 1140 gccggagatg gaagtggaat gggggctgtt gggggcacac cgtccgactg ccgatacata 1200

ctcactccgg gcggtctcgc agaacaaccg ggtcaagcag aacatcaacc agaaagtcca 1260 ctcaatgaga cacagcgact gttgttgttg caacagggct tgctgcctca ctcatcctgt 1320 <210> SEQ ID NO 19 <211> LENGTH: 783 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Syk signaling domain <400> SEQUENCE: 19 acattggaag acaaagaact ggggtctggg aacttcggga cagtcaaaaa ggggtactac 60 cagatgaaaa aagttgtcaa aactgtggcg gtaaaaatct tgaaaaatga agctaatgac 120 cctgcactca aggatgagct tctggcagaa gctaacgtga tgcagcagct tgataatcct 180 tatattgttc gcatgatagg tatatgtgag gcggaaagct ggatgctcgt aatggaaatg 240 gcagaactgg gaccattgaa taaatatctg caacaaaata gacatgtgaa ggataaaaac 300 atcatagagc tcgtacacca agtctctatg gggatgaagt acttggagga gagcaacttc 360 gtgcataggg acttggccgc ccgaaacgta ctgctcgtaa ctcaacatta cgcgaaaatc 420 tcagacttcg gtttgtctaa agcactccgg gcagacgaga actactacaa agcccaaact 480 cacggcaagt ggccagtcaa gtggtacgcg ccggaatgca taaactatta caagtttagt 540 tctaagtctg atgtgtggag cttcggggtt ctgatgtggg aagcctttag ttatggacag 600 aagccctacc gggggatgaa aggaagcgag gtaacagcta tgctggaaaa aggggagcgg 660 atgggctgtc cagcggggtg tcctcgagaa atgtatgatc tcatgaacct gtgttggacc 720 tacgatgtcg agaatcgccc gggctttgct gcggtggaac ttagactgag gaattattac 780 tac 783 <210> SEQ ID NO 20 <211> LENGTH: 789 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Zap70 signaling domain <400> SEQUENCE: 20 ctcattgccg acatcgaact tggttgcggc aacttcggat ctgtgagaca aggcgtctac 60 cggatgagaa agaagcagat tgacgttgca atcaaagtcc tgaagcaggg cacggaaaag 120 gcggacaccg aggagatgat gcgcgaggct cagattatgc accagctcga caatccgtac 180 atcgttagac ttatcggagt ttgccaggca gaagcgttga tgctcgtgat ggagatggca 240 ggcggtggtc ctctgcataa atttttggta ggcaagcgag aagagatccc cgtcagcaat 300 gtagcagaat tgttgcatca agtgagcatg gggatgaagt accttgagga aaaaaatttc 360 gtacatcgcg acctcgctgc gagaaatgtg cttttggtaa atcgccatta cgctaaaatt 420 agtgactttg gactcagtaa ggcattgggt gctgacgact catattacac ggcaagaagc 480 gcaggtaagt ggcctctgaa gtggtatgct cccgagtgca tcaacttccg caagttttct 540 tccaggtctg acgtttggag ctacggtgtc acgatgtggg aagccctgag ctatggtcag 600 aaaccttaca agaaaatgaa gggacctgaa gtcatggcct ttatagagca gggaaagaga 660 atggagtgtc ccccagaatg cccacccgag ctctatgcac tgatgagtga ctgctggatt 720 tacaaatggg aggatcggcc tgactttctt acggttgagc aaaggatgag ggcgtgctat 780 tattctctg 789 <210> SEQ ID NO 21 <211> LENGTH: 183 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI signaling domain <400> SEQUENCE: 21 agaaaggaac tcaagcgcaa gaagaagtgg gacctggaga tttctctcga ctccggtcac 60 gaaaagaagg tcatcagtag cttgcaagag gaccgacact tggaagaaga acttaaatgc 120 caggaacaga aagaggagca gctccaggag ggagtccacc ggaaagaacc acagggagca 180 act 183 <210> SEQ ID NO 22 <211> LENGTH: 231 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2A signaling domain <400> SEQUENCE: 22 tgtcgaaaga agcggatttc agccaatagt acagacccag tgaaagccgc tcaatttgag 60 ccacccggtc gacagatgat cgcaattagg aaacgccaac tggaggaaac gaataatgat 120 tacgaaacgg cagatggggg ctacatgacg ctcaatccta gagctccgac cgacgacgac 180 aagaatatat atctgactct ccctcccaac gaccacgtaa acagtaataa c 231 <210> SEQ ID NO 23 <211> LENGTH: 231 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2C signaling domain <400> SEQUENCE: 23 tgcagaaaga agcggataag tgcaaatagt actgatcccg ttaaagcagc acaatttgag 60 ccgccaggac ggcaaatgat tgcaatcaga aaacgacaac ccgaggaaac caataatgac 120 tacgagaccg ctgacggagg gtatatgacg ttgaatcccc gcgcaccaac ggatgacgat 180 aagaacattt atcttacgct gccccctaac gatcatgtga atagcaataa c 231 <210> SEQ ID NO 24 <211> LENGTH: 75 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR3A signaling domain <400> SEQUENCE: 24 aaaacaaata tccggtcctc tacgagggac tggaaagatc ataaattcaa gtggagaaaa 60 gatcctcagg ataaa 75 <210> SEQ ID NO 25 <211> LENGTH: 168 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 25 aagttgcttg taacaataca cgaccgccgg gagttcgcta agttccaatc agaaaggtct 60 agagcgcggt atgaaatggc atctaacccc ttgtaccgga aacctatctc tacgcacacg 120 gtggatttcg catttaataa gttcaataag agttacaacg gctcagtc 168 <210> SEQ ID NO 26 <211> LENGTH: 888 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MyD88 signaling domain <400> SEQUENCE: 26 atggccgcgg gtggacccgg tgcagggtct gccgcaccgg tgtctagcac cagctcactg 60 ccgctggcag cgttgaacat gagggtaaga agacggctta gtcttttctt gaatgtgcga 120 acgcaggtgg ccgctgactg gacggccctc gctgaggaaa tggacttcga gtacctggag 180 atccggcaac tcgagactca agccgaccct actggaagat tgctcgatgc ctggcaggga 240 aggcccggcg catcagttgg taggttgttg gaactcctca ccaaactcgg gcgagatgat 300 gttcttttgg aacttggccc tagtattgag gaggactgtc aaaaatatat tctgaaacaa 360 caacaggaag aagcggagaa accgttgcaa gtggccgcag tcgattcttc agtgccgcgc 420 acagccgaac tggctggaat tactaccctg gatgatcccc tcggacacat gccggagcgg 480 ttcgacgcct tcatttgcta ttgtccctcc gacatccagt ttgtgcagga aatgattagg 540 caactcgaac aaaccaacta taggcttaaa ctgtgtgtgt ccgatcgaga tgttttgcct 600 ggtacttgcg tatggtctat tgccagcgaa ctcatagaga aacgctgtcg ccgcatggta 660 gtggtcgtat ccgacgacta ccttcagtcc aaagagtgtg acttccagac gaaatttgca 720 ctgtcactga gtcctggagc acaccaaaaa aggctgattc cgatcaagta taaggcgatg 780 aagaaggaat ttccttccat cctgaggttc ataactgtat gcgattacac aaatccgtgt 840 actaaatcct ggttctggac tcgacttgcc aaggcactgt ccctccca 888 <210> SEQ ID NO 27 <211> LENGTH: 1566 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Traf6 signaling domain <400> SEQUENCE: 27 atgtcactcc ttaactgcga aaacagttgt gggagttcac aatccgaaag tgattgttgc 60 gtggcgatgg cgtcttcatg ctctgcggtt accaaggatg actctgtggg aggcaccgca 120 tctaccggaa atctgagctc ttcttttatg gaggaaattc agggctacga cgttgagttt 180 gatcctcctc tcgaatctaa gtatgagtgc cccatatgtc tcatggcgtt gagagaagca 240 gtgcagactc cgtgcggaca tcgcttctgc aaggcgtgta ttataaagag tatacgcgat 300 gcgggtcaca aatgtccagt ggacaacgag atactgcttg aaaatcaact tttccccgac 360 aattttgcaa agagagagat actgtctttg atggttaagt gtccaaacga gggctgcttg 420 cacaaaatgg aactccgaca ccttgaagac caccaggcac actgcgagtt cgccctcatg 480 gattgcccac aatgccagcg cccgttccaa aagtttcaca taaacatcca catactgaag 540 gactgtccta ggagacaagt aagctgtgac aattgcgcag cgtcaatggc gttcgaggac 600 aaggagatac acgatcaaaa ctgtcctctg gcgaatgtga tctgcgaata ttgcaatacg 660 atcttgatcc gcgaacagat gcctaatcat tacgacctcg attgtccgac cgcgccaatt 720 ccttgtactt tttctacctt cggatgtcat gagaaaatgc aacgaaatca cctggctcgc 780 catcttcagg agaatactca gagccacatg cgcatgttgg ctcaagccgt acatagcctt 840 agcgtaatac cggactcagg ttatatatcc gaagtacgga attttcaaga aaccatacat 900 caacttgaag gaaggttggt acgacaggat catcagatac gcgaattgac ggccaagatg 960 gaaacccaga gcatgtatgt cagtgagctt aagcgcacta tccgaaccct ggaggataaa 1020 gttgccgaaa tcgaagctca acaatgcaac gggatataca tttggaaaat aggtaacttc 1080 ggaatgcacc tgaagtgtca agaagaagaa aaacctgtcg ttattcattc ccccggcttt 1140

tatacaggga agcctgggta taagctttgc atgaggctcc acctccaatt gccgacggcg 1200 caaaggtgcg caaattacat ttctctgttt gtccatacta tgcagggtga gtacgatagt 1260 cacttgccgt ggcccttcca gggtaccata cgattgacca tcctggatca gagcgaggcc 1320 cccgtgcgac agaatcatga agaaataatg gatgctaagc cggaactgct cgctttccag 1380 agacctacaa ttccgcgaaa tcctaagggt tttggctatg ttacgttcat gcatctggaa 1440 gcactcagac aaagaacatt cattaaagat gacaccttgc ttgtgcggtg tgaggtgtca 1500 accaggttcg acatgggatc tctcagacgg gaggggttcc aaccgcgctc tacagacgct 1560 ggagtg 1566 <210> SEQ ID NO 28 <211> LENGTH: 290 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(20) <400> SEQUENCE: 28 Met His Pro Gln Val Val Ile Leu Ser Leu Ile Leu His Leu Ala Asp 1 5 10 15 Ser Val Ala Gly Ser Val Lys Val Gly Gly Glu Ala Gly Pro Ser Val 20 25 30 Thr Leu Pro Cys His Tyr Ser Gly Ala Val Thr Ser Met Cys Trp Asn 35 40 45 Arg Gly Ser Cys Ser Leu Phe Thr Cys Gln Asn Gly Ile Val Trp Thr 50 55 60 Asn Gly Thr His Val Thr Tyr Arg Lys Asp Thr Arg Tyr Lys Leu Leu 65 70 75 80 Gly Asp Leu Ser Arg Arg Asp Val Ser Leu Thr Ile Glu Asn Thr Ala 85 90 95 Val Ser Asp Ser Gly Val Tyr Cys Cys Arg Val Glu His Arg Gly Trp 100 105 110 Phe Asn Asp Met Lys Ile Thr Val Ser Leu Glu Ile Val Pro Pro Lys 115 120 125 Val Thr Thr Thr Pro Ile Val Thr Thr Val Pro Thr Val Thr Thr Val 130 135 140 Arg Thr Ser Thr Thr Val Pro Thr Thr Thr Thr Val Pro Thr Thr Thr 145 150 155 160 Val Pro Thr Thr Met Ser Ile Pro Thr Thr Thr Thr Val Leu Thr Thr 165 170 175 Met Thr Val Ser Thr Thr Thr Ser Val Pro Thr Thr Thr Ser Ile Pro 180 185 190 Thr Thr Thr Ser Val Pro Val Thr Thr Thr Val Ser Thr Phe Val Pro 195 200 205 Pro Met Pro Leu Pro Arg Gln Asn His Glu Pro Val Ala Thr Ser Pro 210 215 220 Ser Ser Pro Gln Pro Ala Glu Thr His Pro Thr Thr Leu Gln Gly Ala 225 230 235 240 Ile Arg Arg Glu Pro Thr Ser Ser Pro Leu Tyr Ser Tyr Thr Thr Asp 245 250 255 Gly Asn Asp Thr Val Thr Glu Ser Ser Asp Gly Leu Trp Asn Asn Asn 260 265 270 Gln Thr Gln Leu Phe Leu Glu His Ser Leu Leu Thr Ala Asn Thr Thr 275 280 285 Lys Gly 290 <210> SEQ ID NO 29 <211> LENGTH: 314 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(24) <400> SEQUENCE: 29 Met Ser Lys Glu Pro Leu Ile Leu Trp Leu Met Ile Glu Phe Trp Trp 1 5 10 15 Leu Tyr Leu Thr Pro Val Thr Ser Glu Thr Val Val Thr Glu Val Leu 20 25 30 Gly His Arg Val Thr Leu Pro Cys Leu Tyr Ser Ser Trp Ser His Asn 35 40 45 Ser Asn Ser Met Cys Trp Gly Lys Asp Gln Cys Pro Tyr Ser Gly Cys 50 55 60 Lys Glu Ala Leu Ile Arg Thr Asp Gly Met Arg Val Thr Ser Arg Lys 65 70 75 80 Ser Ala Lys Tyr Arg Leu Gln Gly Thr Ile Pro Arg Gly Asp Val Ser 85 90 95 Leu Thr Ile Leu Asn Pro Ser Glu Ser Asp Ser Gly Val Tyr Cys Cys 100 105 110 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Ile Asn Val Arg 115 120 125 Leu Asn Leu Gln Arg Ala Ser Thr Thr Thr His Arg Thr Ala Thr Thr 130 135 140 Thr Thr Arg Arg Thr Thr Thr Thr Ser Pro Thr Thr Thr Arg Gln Met 145 150 155 160 Thr Thr Thr Pro Ala Ala Leu Pro Thr Thr Val Val Thr Thr Pro Asp 165 170 175 Leu Thr Thr Gly Thr Pro Leu Gln Met Thr Thr Ile Ala Val Phe Thr 180 185 190 Thr Ala Asn Thr Cys Leu Ser Leu Thr Pro Ser Thr Leu Pro Glu Glu 195 200 205 Ala Thr Gly Leu Leu Thr Pro Glu Pro Ser Lys Glu Gly Pro Ile Leu 210 215 220 Thr Ala Glu Ser Glu Thr Val Leu Pro Ser Asp Ser Trp Ser Ser Val 225 230 235 240 Glu Ser Thr Ser Ala Asp Thr Val Leu Leu Thr Ser Lys Glu Ser Lys 245 250 255 Val Trp Asp Leu Pro Ser Thr Ser His Val Ser Met Trp Lys Thr Ser 260 265 270 Asp Ser Val Ser Ser Pro Gln Pro Gly Ala Ser Asp Thr Ala Val Pro 275 280 285 Glu Gln Asn Lys Thr Thr Lys Thr Gly Gln Met Asp Gly Ile Pro Met 290 295 300 Ser Met Lys Asn Glu Met Pro Ile Ser Gln 305 310 <210> SEQ ID NO 30 <211> LENGTH: 161 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FA58C2 binding domain <400> SEQUENCE: 30 Leu Asn Gly Cys Ala Asn Pro Leu Gly Leu Lys Asn Asn Ser Ile Pro 1 5 10 15 Asp Lys Gln Ile Thr Ala Ser Ser Ser Tyr Lys Thr Trp Gly Leu His 20 25 30 Leu Phe Ser Trp Asn Pro Ser Tyr Ala Arg Leu Asp Lys Gln Gly Asn 35 40 45 Phe Asn Ala Trp Val Ala Gly Ser Tyr Gly Asn Asp Gln Trp Leu Gln 50 55 60 Val Asp Leu Gly Ser Ser Lys Glu Val Thr Gly Ile Ile Thr Gln Gly 65 70 75 80 Ala Arg Asn Phe Gly Ser Val Gln Phe Val Ala Ser Tyr Lys Val Ala 85 90 95 Tyr Ser Asn Asp Ser Ala Asn Trp Thr Glu Tyr Gln Asp Pro Arg Thr 100 105 110 Gly Ser Ser Lys Ile Phe Pro Gly Asn Trp Asp Asn His Ser His Lys 115 120 125 Lys Asn Leu Phe Glu Thr Pro Ile Leu Ala Arg Tyr Val Arg Ile Leu 130 135 140 Pro Val Ala Trp His Asn Arg Ile Ala Leu Arg Leu Glu Leu Leu Gly 145 150 155 160 Cys <210> SEQ ID NO 31 <211> LENGTH: 292 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(15) <400> SEQUENCE: 31 Met Trp Phe Leu Thr Thr Leu Leu Leu Trp Val Pro Val Asp Gly Gln 1 5 10 15 Val Asp Thr Thr Lys Ala Val Ile Thr Leu Gln Pro Pro Trp Val Ser 20 25 30 Val Phe Gln Glu Glu Thr Val Thr Leu His Cys Glu Val Leu His Leu 35 40 45 Pro Gly Ser Ser Ser Thr Gln Trp Phe Leu Asn Gly Thr Ala Thr Gln 50 55 60 Thr Ser Thr Pro Ser Tyr Arg Ile Thr Ser Ala Ser Val Asn Asp Ser 65 70 75 80 Gly Glu Tyr Arg Cys Gln Arg Gly Leu Ser Gly Arg Ser Asp Pro Ile 85 90 95 Gln Leu Glu Ile His Arg Gly Trp Leu Leu Leu Gln Val Ser Ser Arg 100 105 110 Val Phe Thr Glu Gly Glu Pro Leu Ala Leu Arg Cys His Ala Trp Lys 115 120 125 Asp Lys Leu Val Tyr Asn Val Leu Tyr Tyr Arg Asn Gly Lys Ala Phe 130 135 140 Lys Phe Phe His Trp Asn Ser Asn Leu Thr Ile Leu Lys Thr Asn Ile 145 150 155 160 Ser His Asn Gly Thr Tyr His Cys Ser Gly Met Gly Lys His Arg Tyr 165 170 175 Thr Ser Ala Gly Ile Ser Val Thr Val Lys Glu Leu Phe Pro Ala Pro 180 185 190

Val Leu Asn Ala Ser Val Thr Ser Pro Leu Leu Glu Gly Asn Leu Val 195 200 205 Thr Leu Ser Cys Glu Thr Lys Leu Leu Leu Gln Arg Pro Gly Leu Gln 210 215 220 Leu Tyr Phe Ser Phe Tyr Met Gly Ser Lys Thr Leu Arg Gly Arg Asn 225 230 235 240 Thr Ser Ser Glu Tyr Gln Ile Leu Thr Ala Arg Arg Glu Asp Ser Gly 245 250 255 Leu Tyr Trp Cys Glu Ala Ala Thr Glu Asp Gly Asn Val Leu Lys Arg 260 265 270 Ser Pro Glu Leu Glu Leu Gln Val Leu Gly Leu Gln Leu Pro Thr Pro 275 280 285 Val Trp Phe His 290 <210> SEQ ID NO 32 <211> LENGTH: 94 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Gas6 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(30) <400> SEQUENCE: 32 Met Ala Pro Ser Leu Ser Pro Gly Pro Ala Ala Leu Arg Arg Ala Pro 1 5 10 15 Gln Leu Leu Leu Leu Leu Leu Ala Ala Glu Cys Ala Leu Ala Ala Leu 20 25 30 Leu Pro Ala Arg Glu Ala Thr Gln Phe Leu Arg Pro Arg Gln Arg Arg 35 40 45 Ala Phe Gln Val Phe Glu Glu Ala Lys Gln Gly His Leu Glu Arg Glu 50 55 60 Cys Val Glu Glu Leu Cys Ser Arg Glu Glu Ala Arg Glu Val Phe Glu 65 70 75 80 Asn Asp Pro Glu Thr Asp Tyr Phe Tyr Pro Arg Tyr Leu Asp 85 90 <210> SEQ ID NO 33 <211> LENGTH: 87 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Protein S binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(24) <400> SEQUENCE: 33 Met Arg Val Leu Gly Gly Arg Cys Gly Ala Leu Leu Ala Cys Leu Leu 1 5 10 15 Leu Val Leu Pro Val Ser Glu Ala Asn Phe Leu Ser Lys Gln Gln Ala 20 25 30 Ser Gln Val Leu Val Arg Lys Arg Arg Ala Asn Ser Leu Leu Glu Glu 35 40 45 Thr Lys Gln Gly Asn Leu Glu Arg Glu Cys Ile Glu Glu Leu Cys Asn 50 55 60 Lys Glu Glu Ala Arg Glu Val Phe Glu Asn Asp Pro Glu Thr Asp Tyr 65 70 75 80 Phe Tyr Pro Lys Tyr Leu Val 85 <210> SEQ ID NO 34 <211> LENGTH: 202 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim3 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(21) <400> SEQUENCE: 34 Met Phe Ser His Leu Pro Phe Asp Cys Val Leu Leu Leu Leu Leu Leu 1 5 10 15 Leu Leu Thr Arg Ser Ser Glu Val Glu Tyr Arg Ala Glu Val Gly Gln 20 25 30 Asn Ala Tyr Leu Pro Cys Phe Tyr Thr Pro Ala Ala Pro Gly Asn Leu 35 40 45 Val Pro Val Cys Trp Gly Lys Gly Ala Cys Pro Val Phe Glu Cys Gly 50 55 60 Asn Val Val Leu Arg Thr Asp Glu Arg Asp Val Asn Tyr Trp Thr Ser 65 70 75 80 Arg Tyr Trp Leu Asn Gly Asp Phe Arg Lys Gly Asp Val Ser Leu Thr 85 90 95 Ile Glu Asn Val Thr Leu Ala Asp Ser Gly Ile Tyr Cys Cys Arg Ile 100 105 110 Gln Ile Pro Gly Ile Met Asn Asp Glu Lys Phe Asn Leu Lys Leu Val 115 120 125 Ile Lys Pro Ala Lys Val Thr Pro Ala Pro Thr Arg Gln Arg Asp Phe 130 135 140 Thr Ala Ala Phe Pro Arg Met Leu Thr Thr Arg Gly His Gly Pro Ala 145 150 155 160 Glu Thr Gln Thr Leu Gly Ser Leu Pro Asp Ile Asn Leu Thr Gln Ile 165 170 175 Ser Thr Leu Ala Asn Glu Leu Arg Asp Ser Arg Leu Ala Asn Asp Leu 180 185 190 Arg Asp Ser Gly Ala Thr Ile Arg Ile Gly 195 200 <210> SEQ ID NO 35 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim1 transmembrane domain <400> SEQUENCE: 35 Ile Tyr Ala Gly Val Cys Ile Ser Val Leu Val Leu Leu Ala Leu Leu 1 5 10 15 Gly Val Ile Ile Ala 20 <210> SEQ ID NO 36 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tim4 transmembrane domain <400> SEQUENCE: 36 Leu Leu Met Ile Ile Ala Pro Ser Leu Gly Phe Val Leu Phe Ala Leu 1 5 10 15 Phe Val Ala Phe Leu 20 <210> SEQ ID NO 37 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI transmembrane domain <400> SEQUENCE: 37 Val Leu Phe Tyr Leu Ala Val Gly Ile Met Phe Leu Val Asn Thr Val 1 5 10 15 Leu Trp Val Thr Ile 20 <210> SEQ ID NO 38 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD8a transmembrane domain <400> SEQUENCE: 38 Ile Tyr Ile Trp Ala Pro Leu Ala Gly Thr Cys Gly Val Leu Leu Leu 1 5 10 15 Ser Leu Val Ile Thr 20 <210> SEQ ID NO 39 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK transmembrane domain <400> SEQUENCE: 39 Phe Gly Cys Phe Cys Gly Phe Ile Leu Ile Gly Leu Ile Leu Tyr Ile 1 5 10 15 Ser Leu Ala Ile Arg 20 <210> SEQ ID NO 40 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl transmembrane domain <400> SEQUENCE: 40 Tyr Val Leu Leu Gly Ala Val Val Ala Ala Ala Cys Val Leu Ile Leu 1 5 10 15 Ala Leu Phe Leu Val 20 <210> SEQ ID NO 41 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 transmembrane domain <400> SEQUENCE: 41 Val Pro Val Val Leu Gly Val Leu Thr Ala Leu Val Thr Ala Ala Ala 1 5 10 15 Leu Ala Leu Ile Leu 20 <210> SEQ ID NO 42 <211> LENGTH: 22 <212> TYPE: PRT

<213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD4 transmembrane domain <400> SEQUENCE: 42 Met Ala Leu Ile Val Leu Gly Gly Val Ala Gly Leu Leu Leu Phe Ile 1 5 10 15 Gly Leu Gly Ile Phe Phe 20 <210> SEQ ID NO 43 <211> LENGTH: 476 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 43 Ala Leu Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser 1 5 10 15 Glu Glu Asp Ser Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe 20 25 30 Cys Arg Arg Ala Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu 35 40 45 Glu Leu Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu 50 55 60 Val Leu Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu 65 70 75 80 Gly Asn Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys 85 90 95 Thr Met Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu 100 105 110 Ser Glu Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg 115 120 125 Leu Leu Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro 130 135 140 Met Val Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu 145 150 155 160 Leu Tyr Ser Arg Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr 165 170 175 Leu Leu Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser 180 185 190 Asn Arg Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu 195 200 205 Arg Asp Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys 210 215 220 Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro 225 230 235 240 Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser 245 250 255 Lys Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr 260 265 270 Arg Gly Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp 275 280 285 Tyr Leu Leu His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp 290 295 300 Glu Leu Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp 305 310 315 320 Arg Pro Thr Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu 325 330 335 Ser Leu Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr 340 345 350 Gln Leu Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr 355 360 365 Gly Leu Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr 370 375 380 Pro Gly Ala Ala Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn 385 390 395 400 Leu Arg Glu Glu Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu 405 410 415 Asp Val Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly 420 425 430 Val Leu Pro Glu Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His 435 440 445 His Ser Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe 450 455 460 Val Asp Asp Ser Leu Glu Asp Ser Glu Val Leu Met 465 470 475 <210> SEQ ID NO 44 <211> LENGTH: 422 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Axl signaling domain <400> SEQUENCE: 44 His Arg Arg Lys Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr 1 5 10 15 Val Glu Arg Gly Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr 20 25 30 Ser Arg Arg Thr Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu 35 40 45 Glu Leu Lys Glu Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val 50 55 60 Ala Leu Gly Lys Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu 65 70 75 80 Gly Gln Leu Asn Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr 85 90 95 Met Lys Ile Ala Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser 100 105 110 Glu Ala Val Cys Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu 115 120 125 Ile Gly Val Cys Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro 130 135 140 Val Val Ile Leu Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu 145 150 155 160 Leu Tyr Ser Arg Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met 165 170 175 Leu Val Lys Phe Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser 180 185 190 Thr Lys Arg Phe Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu 195 200 205 Asn Glu Asn Met Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys 210 215 220 Ile Tyr Asn Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro 225 230 235 240 Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser 245 250 255 Lys Ser Asp Val Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr 260 265 270 Arg Gly Gln Thr Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp 275 280 285 Tyr Leu Arg Gln Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp 290 295 300 Gly Leu Tyr Ala Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp 305 310 315 320 Arg Pro Ser Phe Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys 325 330 335 Ala Leu Pro Pro Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met 340 345 350 Asp Glu Gly Gly Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala 355 360 365 Asp Pro Pro Thr Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr 370 375 380 Ala Ala Glu Val His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr 385 390 395 400 Thr Pro Ser Pro Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro 405 410 415 Gly Gln Glu Asp Gly Ala 420 <210> SEQ ID NO 45 <211> LENGTH: 440 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Tyro3 signaling domain <400> SEQUENCE: 45 Leu Arg Lys Arg Arg Lys Glu Thr Arg Phe Gly Gln Ala Phe Asp Ser 1 5 10 15 Val Met Ala Arg Gly Glu Pro Ala Val His Phe Arg Ala Ala Arg Ser 20 25 30 Phe Asn Arg Glu Arg Pro Glu Arg Ile Glu Ala Thr Leu Asp Ser Leu 35 40 45 Gly Ile Ser Asp Glu Leu Lys Glu Lys Leu Glu Asp Val Leu Ile Pro 50 55 60 Glu Gln Gln Phe Thr Leu Gly Arg Met Leu Gly Lys Gly Glu Phe Gly 65 70 75 80 Ser Val Arg Glu Ala Gln Leu Lys Gln Glu Asp Gly Ser Phe Val Lys 85 90 95 Val Ala Val Lys Met Leu Lys Ala Asp Ile Ile Ala Ser Ser Asp Ile 100 105 110 Glu Glu Phe Leu Arg Glu Ala Ala Cys Met Lys Glu Phe Asp His Pro 115 120 125 His Val Ala Lys Leu Val Gly Val Ser Leu Arg Ser Arg Ala Lys Gly 130 135 140 Arg Leu Pro Ile Pro Met Val Ile Leu Pro Phe Met Lys His Gly Asp 145 150 155 160 Leu His Ala Phe Leu Leu Ala Ser Arg Ile Gly Glu Asn Pro Phe Asn 165 170 175 Leu Pro Leu Gln Thr Leu Ile Arg Phe Met Val Asp Ile Ala Cys Gly 180 185 190 Met Glu Tyr Leu Ser Ser Arg Asn Phe Ile His Arg Asp Leu Ala Ala 195 200 205

Arg Asn Cys Met Leu Ala Glu Asp Met Thr Val Cys Val Ala Asp Phe 210 215 220 Gly Leu Ser Arg Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Cys 225 230 235 240 Ala Ser Lys Leu Pro Val Lys Trp Leu Ala Leu Glu Ser Leu Ala Asp 245 250 255 Asn Leu Tyr Thr Val Gln Ser Asp Val Trp Ala Phe Gly Val Thr Met 260 265 270 Trp Glu Ile Met Thr Arg Gly Gln Thr Pro Tyr Ala Gly Ile Glu Asn 275 280 285 Ala Glu Ile Tyr Asn Tyr Leu Ile Gly Gly Asn Arg Leu Lys Gln Pro 290 295 300 Pro Glu Cys Met Glu Asp Val Tyr Asp Leu Met Tyr Gln Cys Trp Ser 305 310 315 320 Ala Asp Pro Lys Gln Arg Pro Ser Phe Thr Cys Leu Arg Met Glu Leu 325 330 335 Glu Asn Ile Leu Gly Gln Leu Ser Val Leu Ser Ala Ser Gln Asp Pro 340 345 350 Leu Tyr Ile Asn Ile Glu Arg Ala Glu Glu Pro Thr Ala Gly Gly Ser 355 360 365 Leu Glu Leu Pro Gly Arg Asp Gln Pro Tyr Ser Gly Ala Gly Asp Gly 370 375 380 Ser Gly Met Gly Ala Val Gly Gly Thr Pro Ser Asp Cys Arg Tyr Ile 385 390 395 400 Leu Thr Pro Gly Gly Leu Ala Glu Gln Pro Gly Gln Ala Glu His Gln 405 410 415 Pro Glu Ser Pro Leu Asn Glu Thr Gln Arg Leu Leu Leu Leu Gln Gln 420 425 430 Gly Leu Leu Pro His Ser Ser Cys 435 440 <210> SEQ ID NO 46 <211> LENGTH: 261 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Syk signaling domain <400> SEQUENCE: 46 Thr Leu Glu Asp Lys Glu Leu Gly Ser Gly Asn Phe Gly Thr Val Lys 1 5 10 15 Lys Gly Tyr Tyr Gln Met Lys Lys Val Val Lys Thr Val Ala Val Lys 20 25 30 Ile Leu Lys Asn Glu Ala Asn Asp Pro Ala Leu Lys Asp Glu Leu Leu 35 40 45 Ala Glu Ala Asn Val Met Gln Gln Leu Asp Asn Pro Tyr Ile Val Arg 50 55 60 Met Ile Gly Ile Cys Glu Ala Glu Ser Trp Met Leu Val Met Glu Met 65 70 75 80 Ala Glu Leu Gly Pro Leu Asn Lys Tyr Leu Gln Gln Asn Arg His Val 85 90 95 Lys Asp Lys Asn Ile Ile Glu Leu Val His Gln Val Ser Met Gly Met 100 105 110 Lys Tyr Leu Glu Glu Ser Asn Phe Val His Arg Asp Leu Ala Ala Arg 115 120 125 Asn Val Leu Leu Val Thr Gln His Tyr Ala Lys Ile Ser Asp Phe Gly 130 135 140 Leu Ser Lys Ala Leu Arg Ala Asp Glu Asn Tyr Tyr Lys Ala Gln Thr 145 150 155 160 His Gly Lys Trp Pro Val Lys Trp Tyr Ala Pro Glu Cys Ile Asn Tyr 165 170 175 Tyr Lys Phe Ser Ser Lys Ser Asp Val Trp Ser Phe Gly Val Leu Met 180 185 190 Trp Glu Ala Phe Ser Tyr Gly Gln Lys Pro Tyr Arg Gly Met Lys Gly 195 200 205 Ser Glu Val Thr Ala Met Leu Glu Lys Gly Glu Arg Met Gly Cys Pro 210 215 220 Ala Gly Cys Pro Arg Glu Met Tyr Asp Leu Met Asn Leu Cys Trp Thr 225 230 235 240 Tyr Asp Val Glu Asn Arg Pro Gly Phe Ala Ala Val Glu Leu Arg Leu 245 250 255 Arg Asn Tyr Tyr Tyr 260 <210> SEQ ID NO 47 <211> LENGTH: 263 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Zap70 signaling domain <400> SEQUENCE: 47 Leu Ile Ala Asp Ile Glu Leu Gly Cys Gly Asn Phe Gly Ser Val Arg 1 5 10 15 Gln Gly Val Tyr Arg Met Arg Lys Lys Gln Ile Asp Val Ala Ile Lys 20 25 30 Val Leu Lys Gln Gly Thr Glu Lys Ala Asp Thr Glu Glu Met Met Arg 35 40 45 Glu Ala Gln Ile Met His Gln Leu Asp Asn Pro Tyr Ile Val Arg Leu 50 55 60 Ile Gly Val Cys Gln Ala Glu Ala Leu Met Leu Val Met Glu Met Ala 65 70 75 80 Gly Gly Gly Pro Leu His Lys Phe Leu Val Gly Lys Arg Glu Glu Ile 85 90 95 Pro Val Ser Asn Val Ala Glu Leu Leu His Gln Val Ser Met Gly Met 100 105 110 Lys Tyr Leu Glu Glu Lys Asn Phe Val His Arg Asp Leu Ala Ala Arg 115 120 125 Asn Val Leu Leu Val Asn Arg His Tyr Ala Lys Ile Ser Asp Phe Gly 130 135 140 Leu Ser Lys Ala Leu Gly Ala Asp Asp Ser Tyr Tyr Thr Ala Arg Ser 145 150 155 160 Ala Gly Lys Trp Pro Leu Lys Trp Tyr Ala Pro Glu Cys Ile Asn Phe 165 170 175 Arg Lys Phe Ser Ser Arg Ser Asp Val Trp Ser Tyr Gly Val Thr Met 180 185 190 Trp Glu Ala Leu Ser Tyr Gly Gln Lys Pro Tyr Lys Lys Met Lys Gly 195 200 205 Pro Glu Val Met Ala Phe Ile Glu Gln Gly Lys Arg Met Glu Cys Pro 210 215 220 Pro Glu Cys Pro Pro Glu Leu Tyr Ala Leu Met Ser Asp Cys Trp Ile 225 230 235 240 Tyr Lys Trp Glu Asp Arg Pro Asp Phe Leu Thr Val Glu Gln Arg Met 245 250 255 Arg Ala Cys Tyr Tyr Ser Leu 260 <210> SEQ ID NO 48 <211> LENGTH: 61 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaRI signaling domain <400> SEQUENCE: 48 Arg Lys Glu Leu Lys Arg Lys Lys Lys Trp Asp Leu Glu Ile Ser Leu 1 5 10 15 Asp Ser Gly His Glu Lys Lys Val Ile Ser Ser Leu Gln Glu Asp Arg 20 25 30 His Leu Glu Glu Glu Leu Lys Cys Gln Glu Gln Lys Glu Glu Gln Leu 35 40 45 Gln Glu Gly Val His Arg Lys Glu Pro Gln Gly Ala Thr 50 55 60 <210> SEQ ID NO 49 <211> LENGTH: 77 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2A signaling domain <400> SEQUENCE: 49 Cys Arg Lys Lys Arg Ile Ser Ala Asn Ser Thr Asp Pro Val Lys Ala 1 5 10 15 Ala Gln Phe Glu Pro Pro Gly Arg Gln Met Ile Ala Ile Arg Lys Arg 20 25 30 Gln Leu Glu Glu Thr Asn Asn Asp Tyr Glu Thr Ala Asp Gly Gly Tyr 35 40 45 Met Thr Leu Asn Pro Arg Ala Pro Thr Asp Asp Asp Lys Asn Ile Tyr 50 55 60 Leu Thr Leu Pro Pro Asn Asp His Val Asn Ser Asn Asn 65 70 75 <210> SEQ ID NO 50 <211> LENGTH: 77 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR2C signaling domain <400> SEQUENCE: 50 Cys Arg Lys Lys Arg Ile Ser Ala Asn Ser Thr Asp Pro Val Lys Ala 1 5 10 15 Ala Gln Phe Glu Pro Pro Gly Arg Gln Met Ile Ala Ile Arg Lys Arg 20 25 30 Gln Pro Glu Glu Thr Asn Asn Asp Tyr Glu Thr Ala Asp Gly Gly Tyr 35 40 45 Met Thr Leu Asn Pro Arg Ala Pro Thr Asp Asp Asp Lys Asn Ile Tyr 50 55 60 Leu Thr Leu Pro Pro Asn Asp His Val Asn Ser Asn Asn 65 70 75 <210> SEQ ID NO 51 <211> LENGTH: 25 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcgammaR3A signaling domain <400> SEQUENCE: 51 Lys Thr Asn Ile Arg Ser Ser Thr Arg Asp Trp Lys Asp His Lys Phe

1 5 10 15 Lys Trp Arg Lys Asp Pro Gln Asp Lys 20 25 <210> SEQ ID NO 52 <211> LENGTH: 56 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 52 Lys Leu Leu Val Thr Ile His Asp Arg Arg Glu Phe Ala Lys Phe Gln 1 5 10 15 Ser Glu Arg Ser Arg Ala Arg Tyr Glu Met Ala Ser Asn Pro Leu Tyr 20 25 30 Arg Lys Pro Ile Ser Thr His Thr Val Asp Phe Ala Phe Asn Lys Phe 35 40 45 Asn Lys Ser Tyr Asn Gly Ser Val 50 55 <210> SEQ ID NO 53 <211> LENGTH: 296 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MyD88 signaling domain <400> SEQUENCE: 53 Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser 1 5 10 15 Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg 20 25 30 Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr 35 40 45 Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu 50 55 60 Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly 65 70 75 80 Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu 85 90 95 Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp 100 105 110 Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro 115 120 125 Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu 130 135 140 Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly His Met Pro Glu Arg 145 150 155 160 Phe Asp Ala Phe Ile Cys Tyr Cys Pro Ser Asp Ile Gln Phe Val Gln 165 170 175 Glu Met Ile Arg Gln Leu Glu Gln Thr Asn Tyr Arg Leu Lys Leu Cys 180 185 190 Val Ser Asp Arg Asp Val Leu Pro Gly Thr Cys Val Trp Ser Ile Ala 195 200 205 Ser Glu Leu Ile Glu Lys Arg Cys Arg Arg Met Val Val Val Val Ser 210 215 220 Asp Asp Tyr Leu Gln Ser Lys Glu Cys Asp Phe Gln Thr Lys Phe Ala 225 230 235 240 Leu Ser Leu Ser Pro Gly Ala His Gln Lys Arg Leu Ile Pro Ile Lys 245 250 255 Tyr Lys Ala Met Lys Lys Glu Phe Pro Ser Ile Leu Arg Phe Ile Thr 260 265 270 Val Cys Asp Tyr Thr Asn Pro Cys Thr Lys Ser Trp Phe Trp Thr Arg 275 280 285 Leu Ala Lys Ala Leu Ser Leu Pro 290 295 <210> SEQ ID NO 54 <211> LENGTH: 522 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Traf6 signaling domain <400> SEQUENCE: 54 Met Ser Leu Leu Asn Cys Glu Asn Ser Cys Gly Ser Ser Gln Ser Glu 1 5 10 15 Ser Asp Cys Cys Val Ala Met Ala Ser Ser Cys Ser Ala Val Thr Lys 20 25 30 Asp Asp Ser Val Gly Gly Thr Ala Ser Thr Gly Asn Leu Ser Ser Ser 35 40 45 Phe Met Glu Glu Ile Gln Gly Tyr Asp Val Glu Phe Asp Pro Pro Leu 50 55 60 Glu Ser Lys Tyr Glu Cys Pro Ile Cys Leu Met Ala Leu Arg Glu Ala 65 70 75 80 Val Gln Thr Pro Cys Gly His Arg Phe Cys Lys Ala Cys Ile Ile Lys 85 90 95 Ser Ile Arg Asp Ala Gly His Lys Cys Pro Val Asp Asn Glu Ile Leu 100 105 110 Leu Glu Asn Gln Leu Phe Pro Asp Asn Phe Ala Lys Arg Glu Ile Leu 115 120 125 Ser Leu Met Val Lys Cys Pro Asn Glu Gly Cys Leu His Lys Met Glu 130 135 140 Leu Arg His Leu Glu Asp His Gln Ala His Cys Glu Phe Ala Leu Met 145 150 155 160 Asp Cys Pro Gln Cys Gln Arg Pro Phe Gln Lys Phe His Ile Asn Ile 165 170 175 His Ile Leu Lys Asp Cys Pro Arg Arg Gln Val Ser Cys Asp Asn Cys 180 185 190 Ala Ala Ser Met Ala Phe Glu Asp Lys Glu Ile His Asp Gln Asn Cys 195 200 205 Pro Leu Ala Asn Val Ile Cys Glu Tyr Cys Asn Thr Ile Leu Ile Arg 210 215 220 Glu Gln Met Pro Asn His Tyr Asp Leu Asp Cys Pro Thr Ala Pro Ile 225 230 235 240 Pro Cys Thr Phe Ser Thr Phe Gly Cys His Glu Lys Met Gln Arg Asn 245 250 255 His Leu Ala Arg His Leu Gln Glu Asn Thr Gln Ser His Met Arg Met 260 265 270 Leu Ala Gln Ala Val His Ser Leu Ser Val Ile Pro Asp Ser Gly Tyr 275 280 285 Ile Ser Glu Val Arg Asn Phe Gln Glu Thr Ile His Gln Leu Glu Gly 290 295 300 Arg Leu Val Arg Gln Asp His Gln Ile Arg Glu Leu Thr Ala Lys Met 305 310 315 320 Glu Thr Gln Ser Met Tyr Val Ser Glu Leu Lys Arg Thr Ile Arg Thr 325 330 335 Leu Glu Asp Lys Val Ala Glu Ile Glu Ala Gln Gln Cys Asn Gly Ile 340 345 350 Tyr Ile Trp Lys Ile Gly Asn Phe Gly Met His Leu Lys Cys Gln Glu 355 360 365 Glu Glu Lys Pro Val Val Ile His Ser Pro Gly Phe Tyr Thr Gly Lys 370 375 380 Pro Gly Tyr Lys Leu Cys Met Arg Leu His Leu Gln Leu Pro Thr Ala 385 390 395 400 Gln Arg Cys Ala Asn Tyr Ile Ser Leu Phe Val His Thr Met Gln Gly 405 410 415 Glu Tyr Asp Ser His Leu Pro Trp Pro Phe Gln Gly Thr Ile Arg Leu 420 425 430 Thr Ile Leu Asp Gln Ser Glu Ala Pro Val Arg Gln Asn His Glu Glu 435 440 445 Ile Met Asp Ala Lys Pro Glu Leu Leu Ala Phe Gln Arg Pro Thr Ile 450 455 460 Pro Arg Asn Pro Lys Gly Phe Gly Tyr Val Thr Phe Met His Leu Glu 465 470 475 480 Ala Leu Arg Gln Arg Thr Phe Ile Lys Asp Asp Thr Leu Leu Val Arg 485 490 495 Cys Glu Val Ser Thr Arg Phe Asp Met Gly Ser Leu Arg Arg Glu Gly 500 505 510 Phe Gln Pro Arg Ser Thr Asp Ala Gly Val 515 520 <210> SEQ ID NO 55 <211> LENGTH: 138 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 signaling domain <400> SEQUENCE: 55 tataagaaac ggcgcgttca tcttcctcag gagggggcat ttgaaaatac gttgtacttc 60 aacagccaga gcagtccagg tacgtctgat atgaaggatt tggtggggaa cattgaacag 120 aacgagcata gcgttata 138 <210> SEQ ID NO 56 <211> LENGTH: 46 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 signaling domain <400> SEQUENCE: 56 Tyr Lys Lys Arg Arg Val His Leu Pro Gln Glu Gly Ala Phe Glu Asn 1 5 10 15 Thr Leu Tyr Phe Asn Ser Gln Ser Ser Pro Gly Thr Ser Asp Met Lys 20 25 30 Asp Leu Val Gly Asn Ile Glu Gln Asn Glu His Ser Val Ile 35 40 45 <210> SEQ ID NO 57 <211> LENGTH: 1080 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: TIM4 extracellular and transmembrane domains <400> SEQUENCE: 57 ttctctaggc gccggaattc gccaccatgt ctaaaggtct tcttctgctg tggctggtta 60

ctgaactgtg gtggttgtat ctcactcctg cagcaagtga ggataccatc attggtttct 120 tggggcagcc cgtcaccctc ccttgtcact accttagctg gagccagagc agaaatagta 180 tgtgttgggg taagggctcc tgtcctaata gcaaatgtaa tgcagagctc ttgcgaacag 240 acgggacacg gatcatcagt agaaagtcta ctaagtatac cttgcttggg aaggtacaat 300 ttggggaagt gtccctcact attagtaata caaatagagg tgacagcgga gtctattgct 360 gtagaataga agtaccaggt tggtttaacg atgtcaaaaa aaatgtacgg ctcgaattga 420 ggagggctac cactaccaag aaaccaacta caaccacccg ccccactaca accccttacg 480 tcaccacaac aacccctgaa ctgctgccca caactgtgat gaccaccagt gttcttccca 540 ctaccactcc tccccagacc ctggctacta ccgctttctc aacagccgta actacttgtc 600 cctcaactac ccctgggtca ttcagtcagg aaactacaaa ggggtccgct ttcactactg 660 agtcagaaac cctccctgct tctaatcact ctcaacgcag catgatgaca atatcaactg 720 acatcgctgt tctgagacca actggaagca atcccggtat cttgccctcc acatctcagc 780 tgacaacaca aaaaactacc ctgaccacat cagaatccct tcagaagaca actaagtccc 840 accaaatcaa ttcccgacag actattctta taatagcctg ttgtgtgggg tttgtgctga 900 tggttttgtt gttcctggct tttttgcttc gcggcaaggt gactggtgcc aactgtctcc 960 aaaggcacaa aaggccagac aatacggaag attctgattc cgtgcttaac gatatgagcc 1020 acgggcggga cgatgaggat ggtatattca ccttgtgagc ggccgcccct ctccctcccc 1080 <210> SEQ ID NO 58 <211> LENGTH: 1428 <212> TYPE: DNA <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 58 gctcttagga ggagggtgca ggagacaaag tttggtgggg ctttctcaga ggaggatagc 60 cagctcgttg taaactaccg ggccaagaaa tccttttgca gaagagcaat tgaacttaca 120 ttgcaaagcc tcggagtgtc tgaggagctt cagaataaac ttgaggacgt ggtcatcgat 180 cgcaaccttc ttgtgctggg gaaggtcttg ggagagggag agttcgggtc cgtgatggaa 240 ggtaacctta aacaagagga tggaactagc caaaaagtcg ccgtaaagac tatgaagctg 300 gataatttta gtcagcggga aattgaggaa tttctttcag aggccgcttg catgaaggat 360 ttcaaccatc ccaatgttat caggctcctt ggtgtctgta tcgagcttag ttcccagggc 420 atacctaaac ctatggttat actgcctttc atgaagtatg gtgatctgca cacctttctt 480 ctctactccc ggcttaatac cgggccaaag tatatccacc tccaaaccct cttgaagttc 540 atgatggaca tagcacaggg gatggagtac ctttctaata ggaattttct tcacagggat 600 ttggccgccc gaaattgtat gctcagagat gatatgactg tttgcgtcgc agattttgga 660 cttagcaaga aaatctacag tggtgattac tacagacagg gacgcattgc aaagatgcct 720 gtgaagtgga tagccatcga atcactggcc gatagggttt atacttccaa atccgatgtt 780 tgggcctttg gtgtgactat gtgggaaata acaacacggg ggatgactcc ttatcccggt 840 gttcaaaatc atgagatgta cgattatctc ctccacgggc accgacttaa acagcccgag 900 gactgcctgg acgaactgta tgacattatg tactcttgtt ggagcgctga tccattggac 960 cggcccactt tttccgtgct gcgacttcag ctggagaagc tgagtgagtc tctgcctgac 1020 gctcaggata aagagtcaat tatatacatc aacactcagc tccttgaatc ctgtgagggg 1080 atcgcaaacg gaccttcact cactggcttg gacatgaata ttgatcccga ctccattatt 1140 gcttcctgta cacctggagc agctgtgagt gtggtaaccg ctgaggttca tgaaaataac 1200 ttgcgcgaag aaaggtatat actgaatggg ggaaacgagg aatgggaaga cgtatccagt 1260 accccatttg ctgctgtgac ccccgagaag gatggggttc tgccagaaga tagactcacc 1320 aaaaatggtg tttcctggag tcaccattcc acacttcccc ttggcagtcc aagccctgac 1380 gaactccttt ttgtagatga cagccttgag gacagcgaag tgctgatg 1428 <210> SEQ ID NO 59 <211> LENGTH: 2100 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FA58C2-IgG4-CD28-MERTK CER03 chimeric engulfment receptor <400> SEQUENCE: 59 atgttgctgc tcgttacgtc tctgctcctg tgcgaactgc cgcaccccgc cttcctcctg 60 attccgctga acggctgcgc taatccgctc ggtctgaaaa acaattctat acctgataaa 120 caaatcaccg cctcatcctc ttacaagacg tggggactcc atctcttttc ttggaaccca 180 tcttatgctc gactggacaa acaaggcaat ttcaatgcat gggtcgccgg gagttacggt 240 aacgaccaat ggctccaggt agaccttggt agtagtaagg aggtcacggg tatcatcaca 300 cagggggccc ggaatttcgg ttcagtgcag ttcgttgctt cctacaaggt cgcttattca 360 aacgatagtg ctaattggac agagtaccaa gaccctcgca cgggaagtag taagattttc 420 ccaggcaact gggataacca cagtcacaaa aaaaacttgt tcgagacgcc gatattggcg 480 agatatgtcc ggatacttcc ggtcgcgtgg cataacagaa ttgccctgag gctggaattg 540 ctgggatgcg aaagtaaata tggaccgcca tgccccccat gccccatgtt ttgggtgttg 600 gtcgtagtgg gtggagtcct cgcttgctac tcattgctcg taacggttgc ttttattata 660 ttctgggttg ctcttaggag gagggtgcag gagacaaagt ttggtggggc tttctcagag 720 gaggatagcc agctcgttgt aaactaccgg gccaagaaat ccttttgcag aagagcaatt 780 gaacttacat tgcaaagcct cggagtgtct gaggagcttc agaataaact tgaggacgtg 840 gtcatcgatc gcaaccttct tgtgctgggg aaggtcttgg gagagggaga gttcgggtcc 900 gtgatggaag gtaaccttaa acaagaggat ggaactagcc aaaaagtcgc cgtaaagact 960 atgaagctgg ataattttag tcagcgggaa attgaggaat ttctttcaga ggccgcttgc 1020 atgaaggatt tcaaccatcc caatgttatc aggctccttg gtgtctgtat cgagcttagt 1080 tcccagggca tacctaaacc tatggttata ctgcctttca tgaagtatgg tgatctgcac 1140 acctttcttc tctactcccg gcttaatacc gggccaaagt atatccacct ccaaaccctc 1200 ttgaagttca tgatggacat agcacagggg atggagtacc tttctaatag gaattttctt 1260 cacagggatt tggccgcccg aaattgtatg ctcagagatg atatgactgt ttgcgtcgca 1320 gattttggac ttagcaagaa aatctacagt ggtgattact acagacaggg acgcattgca 1380 aagatgcctg tgaagtggat agccatcgaa tcactggccg atagggttta tacttccaaa 1440 tccgatgttt gggcctttgg tgtgactatg tgggaaataa caacacgggg gatgactcct 1500 tatcccggtg ttcaaaatca tgagatgtac gattatctcc tccacgggca ccgacttaaa 1560 cagcccgagg actgcctgga cgaactgtat gacattatgt actcttgttg gagcgctgat 1620 ccattggacc ggcccacttt ttccgtgctg cgacttcagc tggagaagct gagtgagtct 1680 ctgcctgacg ctcaggataa agagtcaatt atatacatca acactcagct ccttgaatcc 1740 tgtgagggga tcgcaaacgg accttcactc actggcttgg acatgaatat tgatcccgac 1800 tccattattg cttcctgtac acctggagca gctgtgagtg tggtaaccgc tgaggttcat 1860 gaaaataact tgcgcgaaga aaggtatata ctgaatgggg gaaacgagga atgggaagac 1920 gtatccagta ccccatttgc tgctgtgacc cccgagaagg atggggttct gccagaagat 1980 agactcacca aaaatggtgt ttcctggagt caccattcca cacttcccct tggcagtcca 2040 agccctgacg aactcctttt tgtagatgac agccttgagg acagcgaagt gctgatgtga 2100 <210> SEQ ID NO 60 <211> LENGTH: 576 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rac1 <400> SEQUENCE: 60 atgcaagcca ttaagtgcgt agtagttggt gatggagccg tcggcaaaac atgcctgctg 60 atctcttata ccacaaacgc attcccgggc gagtacattc ccactgtatt tgacaactac 120 agtgctaacg tcatggtaga tggtaagccg gttaacctcg gactctggga taccgccggc 180 caggaagact atgatagact tagaccgctc agctatccgc aaaccgatgt gttcctgatt 240 tgctttagcc tggtctcccc cgcttcattt gagaatgtga gagcgaagtg gtatccagag 300 gtgcgccatc actgtccgaa cacacccatt atactcgtgg ggactaaact cgacctgagg 360 gatgacaagg acaccatcga aaaactgaaa gaaaagaaac ttacaccaat aacgtaccct 420 cagggtctgg ctatggcaaa agaaattggc gcggtgaaat acctggaatg cagtgcgctc 480 acccagcggg gcttgaagac ggtgttcgat gaggctatac gcgccgtgct gtgtccccca 540 ccagtgaaga aacgaaaacg aaagtgtctt ctcctt 576 <210> SEQ ID NO 61 <211> LENGTH: 645 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rab5 <400> SEQUENCE: 61 atggcgtctc gcggagccac tcgcccaaac ggcccaaaca ctggcaataa aatttgccaa 60 ttcaagttgg tacttctcgg ggaaagtgct gtgggtaagt catctctcgt acttcgcttc 120 gtgaaagggc agtttcacga gttccaagag tctactatcg gagcggcatt cttgacgcag 180 acagtatgtc tggacgacac tactgtaaaa tttgaaatat gggatacagc ggggcaagag 240 aggtatcact ctcttgctcc gatgtattat agaggcgcgc aagcggccat agtcgtatat 300 gatattacca atgaggaatc atttgcacgg gcgaaaaatt gggtaaaaga actgcagcgc 360 caggcgtcac ccaatatagt aattgctttg tctggaaata aggcagattt ggctaacaag 420 cgcgcggtag actttcaaga ggctcaaagc tacgcagacg acaatagttt gctgttcatg 480 gaaacatcag cgaaaactag tatgaatgta aacgaaatct tcatggcaat cgctaagaaa 540 ctcccaaaaa acgagccgca gaaccctggg gccaacagcg caaggggaag aggcgttgac 600 ttgactgagc cgactcaacc aaccagaaac caatgctgtt ccaac 645 <210> SEQ ID NO 62 <211> LENGTH: 1281 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Rac1-P2A-Rab5a construct <400> SEQUENCE: 62 atgcaagcca ttaagtgcgt agtagttggt gatggagccg tcggcaaaac atgcctgctg 60 atctcttata ccacaaacgc attcccgggc gagtacattc ccactgtatt tgacaactac 120 agtgctaacg tcatggtaga tggtaagccg gttaacctcg gactctggga taccgccggc 180

caggaagact atgatagact tagaccgctc agctatccgc aaaccgatgt gttcctgatt 240 tgctttagcc tggtctcccc cgcttcattt gagaatgtga gagcgaagtg gtatccagag 300 gtgcgccatc actgtccgaa cacacccatt atactcgtgg ggactaaact cgacctgagg 360 gatgacaagg acaccatcga aaaactgaaa gaaaagaaac ttacaccaat aacgtaccct 420 cagggtctgg ctatggcaaa agaaattggc gcggtgaaat acctggaatg cagtgcgctc 480 acccagcggg gcttgaagac ggtgttcgat gaggctatac gcgccgtgct gtgtccccca 540 ccagtgaaga aacgaaaacg aaagtgtctt ctccttgcca ccaacttcag cctgctgaag 600 caggccggcg acgtggagga gaaccccggc cccatggcgt ctcgcggagc cactcgccca 660 aacggcccaa acactggcaa taaaatttgc caattcaagt tggtacttct cggggaaagt 720 gctgtgggta agtcatctct cgtacttcgc ttcgtgaaag ggcagtttca cgagttccaa 780 gagtctacta tcggagcggc attcttgacg cagacagtat gtctggacga cactactgta 840 aaatttgaaa tatgggatac agcggggcaa gagaggtatc actctcttgc tccgatgtat 900 tatagaggcg cgcaagcggc catagtcgta tatgatatta ccaatgagga atcatttgca 960 cgggcgaaaa attgggtaaa agaactgcag cgccaggcgt cacccaatat agtaattgct 1020 ttgtctggaa ataaggcaga tttggctaac aagcgcgcgg tagactttca agaggctcaa 1080 agctacgcag acgacaatag tttgctgttc atggaaacat cagcgaaaac tagtatgaat 1140 gtaaacgaaa tcttcatggc aatcgctaag aaactcccaa aaaacgagcc gcagaaccct 1200 ggggccaaca gcgcaagggg aagaggcgtt gacttgactg agccgactca accaaccaga 1260 aaccaatgct gttccaactg a 1281 <210> SEQ ID NO 63 <211> LENGTH: 1455 <212> TYPE: DNA <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: FA58C2-IgG4-CD28-Syk CER04 chimeric engulfment receptor <400> SEQUENCE: 63 atgttgctgc tcgttacgtc tctgctcctg tgcgaactgc cgcaccccgc cttcctcctg 60 attccgctga acggctgcgc taatccgctc ggtctgaaaa acaattctat acctgataaa 120 caaatcaccg cctcatcctc ttacaagacg tggggactcc atctcttttc ttggaaccca 180 tcttatgctc gactggacaa acaaggcaat ttcaatgcat gggtcgccgg gagttacggt 240 aacgaccaat ggctccaggt agaccttggt agtagtaagg aggtcacggg tatcatcaca 300 cagggggccc ggaatttcgg ttcagtgcag ttcgttgctt cctacaaggt cgcttattca 360 aacgatagtg ctaattggac agagtaccaa gaccctcgca cgggaagtag taagattttc 420 ccaggcaact gggataacca cagtcacaaa aaaaacttgt tcgagacgcc gatattggcg 480 agatatgtcc ggatacttcc ggtcgcgtgg cataacagaa ttgccctgag gctggaattg 540 ctgggatgcg aaagtaaata tggaccgcca tgccccccat gccccatgtt ttgggtgttg 600 gtcgtagtgg gtggagtcct cgcttgctac tcattgctcg taacggttgc ttttattata 660 ttctgggtta cactcgagga taaagagctc ggatctggta atttcggcac agttaagaaa 720 gggtactacc aaatgaagaa agttgttaag actgtagccg tcaagatact caaaaacgaa 780 gcgaatgatc cggcgctgaa agacgaattg ctcgcggaag cgaacgtgat gcaacagctg 840 gataatccct acattgtcag gatgatagga atatgtgagg ctgaaagctg gatgcttgtt 900 atggagatgg cggagcttgg acccctgaac aaatacctcc agcagaatcg gcatgtgaag 960 gataagaata tcatagaatt ggtccaccag gtttcaatgg gtatgaagta tctggaagaa 1020 agtaacttcg ttcatcggga cttggccgcg cgcaatgtct tgcttgtcac gcaacactac 1080 gccaaaatat ccgacttcgg attgagtaag gccctgcgag cagacgaaaa ttattataag 1140 gctcagacac atggaaaatg gcctgtaaag tggtacgcgc ctgagtgcat caactactac 1200 aagttttcaa gtaaatctga tgtatggagc tttggtgtgc tgatgtggga agctttttct 1260 tatggccaaa aaccgtatag aggaatgaag ggatcagaag tcaccgcaat gctcgaaaaa 1320 ggtgaaagga tggggtgccc cgcgggatgc cctcgagaga tgtatgacct gatgaacctt 1380 tgctggactt atgatgtaga gaatagacct gggttcgcag ccgttgagtt gcgcctcagg 1440 aattactact attga 1455 <210> SEQ ID NO 64 <211> LENGTH: 783 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GMCSF-FMC63-IgG4-CD28-MERTK CER40 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: GM-CSF signal peptide <400> SEQUENCE: 64 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Thr Thr Ser Ser -5 1 5 10 Leu Ser Ala Ser Leu Gly Asp Arg Val Thr Ile Ser Cys Arg Ala Ser 15 20 25 Gln Asp Ile Ser Lys Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly 30 35 40 Thr Val Lys Leu Leu Ile Tyr His Thr Ser Arg Leu His Ser Gly Val 45 50 55 Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr 60 65 70 Ile Ser Asn Leu Glu Gln Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln 75 80 85 90 Gly Asn Thr Leu Pro Tyr Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile 95 100 105 Thr Gly Ser Thr Ser Gly Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser 110 115 120 Thr Lys Gly Glu Val Lys Leu Gln Glu Ser Gly Pro Gly Leu Val Ala 125 130 135 Pro Ser Gln Ser Leu Ser Val Thr Cys Thr Val Ser Gly Val Ser Leu 140 145 150 Pro Asp Tyr Gly Val Ser Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu 155 160 165 170 Glu Trp Leu Gly Val Ile Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser 175 180 185 Ala Leu Lys Ser Arg Leu Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln 190 195 200 Val Phe Leu Lys Met Asn Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr 205 210 215 Tyr Cys Ala Lys His Tyr Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr 220 225 230 Trp Gly Gln Gly Thr Ser Val Thr Val Ser Ser Glu Ser Lys Tyr Gly 235 240 245 250 Pro Pro Cys Pro Pro Cys Pro Met Phe Trp Val Leu Val Val Val Gly 255 260 265 Gly Val Leu Ala Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile 270 275 280 Phe Trp Val Ala Leu Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly 285 290 295 Ala Phe Ser Glu Glu Asp Ser Gln Leu Val Val Asn Tyr Arg Ala Lys 300 305 310 Lys Ser Phe Cys Arg Arg Ala Ile Glu Leu Thr Leu Gln Ser Leu Gly 315 320 325 330 Val Ser Glu Glu Leu Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg 335 340 345 Asn Leu Leu Val Leu Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser 350 355 360 Val Met Glu Gly Asn Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val 365 370 375 Ala Val Lys Thr Met Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu 380 385 390 Glu Phe Leu Ser Glu Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn 395 400 405 410 Val Ile Arg Leu Leu Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile 415 420 425 Pro Lys Pro Met Val Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His 430 435 440 Thr Phe Leu Leu Tyr Ser Arg Leu Asn Thr Gly Pro Lys Tyr Ile His 445 450 455 Leu Gln Thr Leu Leu Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu 460 465 470 Tyr Leu Ser Asn Arg Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn 475 480 485 490 Cys Met Leu Arg Asp Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu 495 500 505 Ser Lys Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala 510 515 520 Lys Met Pro Val Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val 525 530 535 Tyr Thr Ser Lys Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu 540 545 550 Ile Thr Thr Arg Gly Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu 555 560 565 570 Met Tyr Asp Tyr Leu Leu His Gly His Arg Leu Lys Gln Pro Glu Asp 575 580 585 Cys Leu Asp Glu Leu Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp 590 595 600 Pro Leu Asp Arg Pro Thr Phe Ser Val Leu Arg Leu Gln Leu Glu Lys 605 610 615 Leu Ser Glu Ser Leu Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr 620 625 630 Ile Asn Thr Gln Leu Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro 635 640 645 650 Ser Leu Thr Gly Leu Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala 655 660 665 Ser Cys Thr Pro Gly Ala Ala Val Ser Val Val Thr Ala Glu Val His 670 675 680 Glu Asn Asn Leu Arg Glu Glu Arg Tyr Ile Leu Asn Gly Gly Asn Glu 685 690 695 Glu Trp Glu Asp Val Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu

700 705 710 Lys Asp Gly Val Leu Pro Glu Asp Arg Leu Thr Lys Asn Gly Val Ser 715 720 725 730 Trp Ser His His Ser Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu 735 740 745 Leu Leu Phe Val Asp Asp Ser Leu Glu Asp Ser Glu Val Leu Met 750 755 760 <210> SEQ ID NO 65 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: GM-CSF signal peptide <400> SEQUENCE: 65 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro 1 5 10 15 Ala Phe Leu Leu Ile Pro 20 <210> SEQ ID NO 66 <211> LENGTH: 245 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: anti-CD19 FMC63 scFv <400> SEQUENCE: 66 Asp Ile Gln Met Thr Gln Thr Thr Ser Ser Leu Ser Ala Ser Leu Gly 1 5 10 15 Asp Arg Val Thr Ile Ser Cys Arg Ala Ser Gln Asp Ile Ser Lys Tyr 20 25 30 Leu Asn Trp Tyr Gln Gln Lys Pro Asp Gly Thr Val Lys Leu Leu Ile 35 40 45 Tyr His Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Gly 50 55 60 Ser Gly Ser Gly Thr Asp Tyr Ser Leu Thr Ile Ser Asn Leu Glu Gln 65 70 75 80 Glu Asp Ile Ala Thr Tyr Phe Cys Gln Gln Gly Asn Thr Leu Pro Tyr 85 90 95 Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Thr Gly Ser Thr Ser Gly 100 105 110 Ser Gly Lys Pro Gly Ser Gly Glu Gly Ser Thr Lys Gly Glu Val Lys 115 120 125 Leu Gln Glu Ser Gly Pro Gly Leu Val Ala Pro Ser Gln Ser Leu Ser 130 135 140 Val Thr Cys Thr Val Ser Gly Val Ser Leu Pro Asp Tyr Gly Val Ser 145 150 155 160 Trp Ile Arg Gln Pro Pro Arg Lys Gly Leu Glu Trp Leu Gly Val Ile 165 170 175 Trp Gly Ser Glu Thr Thr Tyr Tyr Asn Ser Ala Leu Lys Ser Arg Leu 180 185 190 Thr Ile Ile Lys Asp Asn Ser Lys Ser Gln Val Phe Leu Lys Met Asn 195 200 205 Ser Leu Gln Thr Asp Asp Thr Ala Ile Tyr Tyr Cys Ala Lys His Tyr 210 215 220 Tyr Tyr Gly Gly Ser Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr Ser 225 230 235 240 Val Thr Val Ser Ser 245 <210> SEQ ID NO 67 <211> LENGTH: 12 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: modified IgG4 hinge region <400> SEQUENCE: 67 Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro 1 5 10 <210> SEQ ID NO 68 <211> LENGTH: 27 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD28 transmembrane domain <400> SEQUENCE: 68 Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala Cys Tyr Ser Leu 1 5 10 15 Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val 20 25 <210> SEQ ID NO 69 <211> LENGTH: 473 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 69 Lys Arg Val Gln Glu Thr Lys Phe Gly Asn Ala Phe Thr Glu Glu Asp 1 5 10 15 Ser Glu Leu Val Val Asn Tyr Ile Ala Lys Lys Ser Phe Cys Arg Arg 20 25 30 Ala Ile Glu Leu Thr Leu His Ser Leu Gly Val Ser Glu Glu Leu Gln 35 40 45 Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Ile Leu Gly 50 55 60 Lys Ile Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu 65 70 75 80 Lys Gln Glu Asp Gly Thr Ser Leu Lys Val Ala Val Lys Thr Met Lys 85 90 95 Leu Asp Asn Ser Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala 100 105 110 Ala Cys Met Lys Asp Phe Ser His Pro Asn Val Ile Arg Leu Leu Gly 115 120 125 Val Cys Ile Glu Met Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile 130 135 140 Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Tyr Leu Leu Tyr Ser 145 150 155 160 Arg Leu Glu Thr Gly Pro Lys His Ile Pro Leu Gln Thr Leu Leu Lys 165 170 175 Phe Met Val Asp Ile Ala Leu Gly Met Glu Tyr Leu Ser Asn Arg Asn 180 185 190 Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp 195 200 205 Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser 210 215 220 Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp 225 230 235 240 Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp 245 250 255 Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Met 260 265 270 Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu 275 280 285 His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr 290 295 300 Glu Ile Met Tyr Ser Cys Trp Arg Thr Asp Pro Leu Asp Arg Pro Thr 305 310 315 320 Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Leu Glu Ser Leu Pro 325 330 335 Asp Val Arg Asn Gln Ala Asp Val Ile Tyr Val Asn Thr Gln Leu Leu 340 345 350 Glu Ser Ser Glu Gly Leu Ala Gln Gly Ser Thr Leu Ala Pro Leu Asp 355 360 365 Leu Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Arg Ala 370 375 380 Ala Ile Ser Val Val Thr Ala Glu Val His Asp Ser Lys Pro His Glu 385 390 395 400 Gly Arg Tyr Ile Leu Asn Gly Gly Ser Glu Glu Trp Glu Asp Leu Thr 405 410 415 Ser Ala Pro Ser Ala Ala Val Thr Ala Glu Lys Asn Ser Val Leu Pro 420 425 430 Gly Glu Arg Leu Val Arg Asn Gly Val Ser Trp Ser His Ser Ser Met 435 440 445 Leu Pro Leu Gly Ser Ser Leu Pro Asp Glu Leu Leu Phe Ala Asp Asp 450 455 460 Ser Ser Glu Gly Ser Glu Val Leu Met 465 470 <210> SEQ ID NO 70 <211> LENGTH: 484 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GMCSF-FA58C2-IgG4-CD28-SYK CER04 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: GM-CSF signal peptide <400> SEQUENCE: 70 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Leu Asn Gly Cys Ala Asn Pro Leu Gly Leu -5 1 5 10 Lys Asn Asn Ser Ile Pro Asp Lys Gln Ile Thr Ala Ser Ser Ser Tyr 15 20 25 Lys Thr Trp Gly Leu His Leu Phe Ser Trp Asn Pro Ser Tyr Ala Arg 30 35 40 Leu Asp Lys Gln Gly Asn Phe Asn Ala Trp Val Ala Gly Ser Tyr Gly 45 50 55 Asn Asp Gln Trp Leu Gln Val Asp Leu Gly Ser Ser Lys Glu Val Thr 60 65 70 Gly Ile Ile Thr Gln Gly Ala Arg Asn Phe Gly Ser Val Gln Phe Val 75 80 85 90 Ala Ser Tyr Lys Val Ala Tyr Ser Asn Asp Ser Ala Asn Trp Thr Glu

95 100 105 Tyr Gln Asp Pro Arg Thr Gly Ser Ser Lys Ile Phe Pro Gly Asn Trp 110 115 120 Asp Asn His Ser His Lys Lys Asn Leu Phe Glu Thr Pro Ile Leu Ala 125 130 135 Arg Tyr Val Arg Ile Leu Pro Val Ala Trp His Asn Arg Ile Ala Leu 140 145 150 Arg Leu Glu Leu Leu Gly Cys Glu Ser Lys Tyr Gly Pro Pro Cys Pro 155 160 165 170 Pro Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala 175 180 185 Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Thr 190 195 200 Leu Glu Asp Lys Glu Leu Gly Ser Gly Asn Phe Gly Thr Val Lys Lys 205 210 215 Gly Tyr Tyr Gln Met Lys Lys Val Val Lys Thr Val Ala Val Lys Ile 220 225 230 Leu Lys Asn Glu Ala Asn Asp Pro Ala Leu Lys Asp Glu Leu Leu Ala 235 240 245 250 Glu Ala Asn Val Met Gln Gln Leu Asp Asn Pro Tyr Ile Val Arg Met 255 260 265 Ile Gly Ile Cys Glu Ala Glu Ser Trp Met Leu Val Met Glu Met Ala 270 275 280 Glu Leu Gly Pro Leu Asn Lys Tyr Leu Gln Gln Asn Arg His Val Lys 285 290 295 Asp Lys Asn Ile Ile Glu Leu Val His Gln Val Ser Met Gly Met Lys 300 305 310 Tyr Leu Glu Glu Ser Asn Phe Val His Arg Asp Leu Ala Ala Arg Asn 315 320 325 330 Val Leu Leu Val Thr Gln His Tyr Ala Lys Ile Ser Asp Phe Gly Leu 335 340 345 Ser Lys Ala Leu Arg Ala Asp Glu Asn Tyr Tyr Lys Ala Gln Thr His 350 355 360 Gly Lys Trp Pro Val Lys Trp Tyr Ala Pro Glu Cys Ile Asn Tyr Tyr 365 370 375 Lys Phe Ser Ser Lys Ser Asp Val Trp Ser Phe Gly Val Leu Met Trp 380 385 390 Glu Ala Phe Ser Tyr Gly Gln Lys Pro Tyr Arg Gly Met Lys Gly Ser 395 400 405 410 Glu Val Thr Ala Met Leu Glu Lys Gly Glu Arg Met Gly Cys Pro Ala 415 420 425 Gly Cys Pro Arg Glu Met Tyr Asp Leu Met Asn Leu Cys Trp Thr Tyr 430 435 440 Asp Val Glu Asn Arg Pro Gly Phe Ala Ala Val Glu Leu Arg Leu Arg 445 450 455 Asn Tyr Tyr Tyr 460 <210> SEQ ID NO 71 <211> LENGTH: 776 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4-MERTK CER01 mouse chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 71 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met 750 <210> SEQ ID NO 72 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 72 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp 1 5 10 15 Leu Tyr Leu Thr Pro Ala 20 <210> SEQ ID NO 73

<211> LENGTH: 257 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain without signal peptide <400> SEQUENCE: 73 Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu Gly Gln Pro Val Thr Leu 1 5 10 15 Pro Cys His Tyr Leu Ser Trp Ser Gln Ser Arg Asn Ser Met Cys Trp 20 25 30 Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys Asn Ala Glu Leu Leu Arg 35 40 45 Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys Ser Thr Lys Tyr Thr Leu 50 55 60 Leu Gly Lys Val Gln Phe Gly Glu Val Ser Leu Thr Ile Ser Asn Thr 65 70 75 80 Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys Arg Ile Glu Val Pro Gly 85 90 95 Trp Phe Asn Asp Val Lys Lys Asn Val Arg Leu Glu Leu Arg Arg Ala 100 105 110 Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr Arg Pro Thr Thr Thr Pro 115 120 125 Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu Pro Thr Thr Val Met Thr 130 135 140 Thr Ser Val Leu Pro Thr Thr Thr Pro Pro Gln Thr Leu Ala Thr Thr 145 150 155 160 Ala Phe Ser Thr Ala Val Thr Thr Cys Pro Ser Thr Thr Pro Gly Ser 165 170 175 Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala Phe Thr Thr Glu Ser Glu 180 185 190 Thr Leu Pro Ala Ser Asn His Ser Gln Arg Ser Met Met Thr Ile Ser 195 200 205 Thr Asp Ile Ala Val Leu Arg Pro Thr Gly Ser Asn Pro Gly Ile Leu 210 215 220 Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys Thr Thr Leu Thr Thr Ser 225 230 235 240 Glu Ser Leu Gln Lys Thr Thr Lys Ser His Gln Ile Asn Ser Arg Gln 245 250 255 Thr <210> SEQ ID NO 74 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 transmembrane domain <400> SEQUENCE: 74 Ile Leu Ile Ile Ala Cys Cys Val Gly Phe Val Leu Met Val Leu Leu 1 5 10 15 Phe Leu Ala Phe Leu 20 <210> SEQ ID NO 75 <211> LENGTH: 699 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: GMCSF-FA58C2-IgG4-CD28-MERTK CER03 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 75 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Leu Asn Gly Cys Ala Asn Pro Leu Gly Leu -5 1 5 10 Lys Asn Asn Ser Ile Pro Asp Lys Gln Ile Thr Ala Ser Ser Ser Tyr 15 20 25 Lys Thr Trp Gly Leu His Leu Phe Ser Trp Asn Pro Ser Tyr Ala Arg 30 35 40 Leu Asp Lys Gln Gly Asn Phe Asn Ala Trp Val Ala Gly Ser Tyr Gly 45 50 55 Asn Asp Gln Trp Leu Gln Val Asp Leu Gly Ser Ser Lys Glu Val Thr 60 65 70 Gly Ile Ile Thr Gln Gly Ala Arg Asn Phe Gly Ser Val Gln Phe Val 75 80 85 90 Ala Ser Tyr Lys Val Ala Tyr Ser Asn Asp Ser Ala Asn Trp Thr Glu 95 100 105 Tyr Gln Asp Pro Arg Thr Gly Ser Ser Lys Ile Phe Pro Gly Asn Trp 110 115 120 Asp Asn His Ser His Lys Lys Asn Leu Phe Glu Thr Pro Ile Leu Ala 125 130 135 Arg Tyr Val Arg Ile Leu Pro Val Ala Trp His Asn Arg Ile Ala Leu 140 145 150 Arg Leu Glu Leu Leu Gly Cys Glu Ser Lys Tyr Gly Pro Pro Cys Pro 155 160 165 170 Pro Cys Pro Met Phe Trp Val Leu Val Val Val Gly Gly Val Leu Ala 175 180 185 Cys Tyr Ser Leu Leu Val Thr Val Ala Phe Ile Ile Phe Trp Val Ala 190 195 200 Leu Arg Arg Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu 205 210 215 Glu Asp Ser Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys 220 225 230 Arg Arg Ala Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu 235 240 245 250 Leu Gln Asn Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val 255 260 265 Leu Gly Lys Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly 270 275 280 Asn Leu Lys Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr 285 290 295 Met Lys Leu Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser 300 305 310 Glu Ala Ala Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu 315 320 325 330 Leu Gly Val Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met 335 340 345 Val Ile Leu Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu 350 355 360 Tyr Ser Arg Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu 365 370 375 Leu Lys Phe Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn 380 385 390 Arg Asn Phe Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg 395 400 405 410 Asp Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile 415 420 425 Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val 430 435 440 Lys Trp Ile Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys 445 450 455 Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg 460 465 470 Gly Met Thr Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr 475 480 485 490 Leu Leu His Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu 495 500 505 Leu Tyr Asp Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg 510 515 520 Pro Thr Phe Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser 525 530 535 Leu Pro Asp Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln 540 545 550 Leu Leu Glu Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly 555 560 565 570 Leu Asp Met Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro 575 580 585 Gly Ala Ala Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu 590 595 600 Arg Glu Glu Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp 605 610 615 Val Ser Ser Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val 620 625 630 Leu Pro Glu Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His 635 640 645 650 Ser Thr Leu Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val 655 660 665 Asp Asp Ser Leu Glu Asp Ser Glu Val Leu Met 670 675 <210> SEQ ID NO 76 <211> LENGTH: 192 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rac1 <400> SEQUENCE: 76 Met Gln Ala Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys 1 5 10 15 Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Ala Phe Pro Gly Glu Tyr 20 25 30 Ile Pro Thr Val Phe Asp Asn Tyr Ser Ala Asn Val Met Val Asp Gly 35 40 45 Lys Pro Val Asn Leu Gly Leu Trp Asp Thr Ala Gly Gln Glu Asp Tyr 50 55 60 Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Asp Val Phe Leu Ile 65 70 75 80 Cys Phe Ser Leu Val Ser Pro Ala Ser Phe Glu Asn Val Arg Ala Lys 85 90 95 Trp Tyr Pro Glu Val Arg His His Cys Pro Asn Thr Pro Ile Ile Leu 100 105 110

Val Gly Thr Lys Leu Asp Leu Arg Asp Asp Lys Asp Thr Ile Glu Lys 115 120 125 Leu Lys Glu Lys Lys Leu Thr Pro Ile Thr Tyr Pro Gln Gly Leu Ala 130 135 140 Met Ala Lys Glu Ile Gly Ala Val Lys Tyr Leu Glu Cys Ser Ala Leu 145 150 155 160 Thr Gln Arg Gly Leu Lys Thr Val Phe Asp Glu Ala Ile Arg Ala Val 165 170 175 Leu Cys Pro Pro Pro Val Lys Lys Arg Lys Arg Lys Cys Leu Leu Leu 180 185 190 <210> SEQ ID NO 77 <211> LENGTH: 215 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rab5 <400> SEQUENCE: 77 Met Ala Ser Arg Gly Ala Thr Arg Pro Asn Gly Pro Asn Thr Gly Asn 1 5 10 15 Lys Ile Cys Gln Phe Lys Leu Val Leu Leu Gly Glu Ser Ala Val Gly 20 25 30 Lys Ser Ser Leu Val Leu Arg Phe Val Lys Gly Gln Phe His Glu Phe 35 40 45 Gln Glu Ser Thr Ile Gly Ala Ala Phe Leu Thr Gln Thr Val Cys Leu 50 55 60 Asp Asp Thr Thr Val Lys Phe Glu Ile Trp Asp Thr Ala Gly Gln Glu 65 70 75 80 Arg Tyr His Ser Leu Ala Pro Met Tyr Tyr Arg Gly Ala Gln Ala Ala 85 90 95 Ile Val Val Tyr Asp Ile Thr Asn Glu Glu Ser Phe Ala Arg Ala Lys 100 105 110 Asn Trp Val Lys Glu Leu Gln Arg Gln Ala Ser Pro Asn Ile Val Ile 115 120 125 Ala Leu Ser Gly Asn Lys Ala Asp Leu Ala Asn Lys Arg Ala Val Asp 130 135 140 Phe Gln Glu Ala Gln Ser Tyr Ala Asp Asp Asn Ser Leu Leu Phe Met 145 150 155 160 Glu Thr Ser Ala Lys Thr Ser Met Asn Val Asn Glu Ile Phe Met Ala 165 170 175 Ile Ala Lys Lys Leu Pro Lys Asn Glu Pro Gln Asn Pro Gly Ala Asn 180 185 190 Ser Ala Arg Gly Arg Gly Val Asp Leu Thr Glu Pro Thr Gln Pro Thr 195 200 205 Arg Asn Gln Cys Cys Ser Asn 210 215 <210> SEQ ID NO 78 <211> LENGTH: 155 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated MyD88 without TIR domain <400> SEQUENCE: 78 Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser 1 5 10 15 Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg 20 25 30 Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr 35 40 45 Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu 50 55 60 Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly 65 70 75 80 Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu 85 90 95 Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp 100 105 110 Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro 115 120 125 Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu 130 135 140 Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly 145 150 155 <210> SEQ ID NO 79 <211> LENGTH: 455 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-tMyD88 CER15 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 79 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly 430 <210> SEQ ID NO 80 <211> LENGTH: 596 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-MyD88 CER16 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 80 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly His Met Pro Glu Arg Phe Asp Ala Phe 430 435 440 Ile Cys Tyr Cys Pro Ser Asp Ile Gln Phe Val Gln Glu Met Ile Arg 445 450 455 Gln Leu Glu Gln Thr Asn Tyr Arg Leu Lys Leu Cys Val Ser Asp Arg 460 465 470 Asp Val Leu Pro Gly Thr Cys Val Trp Ser Ile Ala Ser Glu Leu Ile 475 480 485 490 Glu Lys Arg Cys Arg Arg Met Val Val Val Val Ser Asp Asp Tyr Leu 495 500 505 Gln Ser Lys Glu Cys Asp Phe Gln Thr Lys Phe Ala Leu Ser Leu Ser 510 515 520 Pro Gly Ala His Gln Lys Arg Leu Ile Pro Ile Lys Tyr Lys Ala Met 525 530 535 Lys Lys Glu Phe Pro Ser Ile Leu Arg Phe Ile Thr Val Cys Asp Tyr 540 545 550 Thr Asn Pro Cys Thr Lys Ser Trp Phe Trp Thr Arg Leu Ala Lys Ala 555 560 565 570 Leu Ser Leu Pro <210> SEQ ID NO 81 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <221> NAME/KEY: PEPTIDE <222> LOCATION: (0)...(0) <223> OTHER INFORMATION: DAP12 transmembrane domain <400> SEQUENCE: 81 Gly Val Leu Ala Gly Ile Val Met Gly Asp Leu Val Leu Thr Val Leu 1 5 10 15 Ile Ala Leu Ala Val 20 <210> SEQ ID NO 82 <211> LENGTH: 52 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: DAP12 signaling domain <400> SEQUENCE: 82 Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala 1 5 10 15 Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu 20 25 30 Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg 35 40 45 Pro Tyr Tyr Lys 50 <210> SEQ ID NO 83 <211> LENGTH: 740 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-Tyro3 CER08 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 83 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Leu Arg Lys Arg 270 275 280 Arg Lys Glu Thr Arg Phe Gly Gln Ala Phe Asp Ser Val Met Ala Arg 285 290 295 Gly Glu Pro Ala Val His Phe Arg Ala Ala Arg Ser Phe Asn Arg Glu 300 305 310 Arg Pro Glu Arg Ile Glu Ala Thr Leu Asp Ser Leu Gly Ile Ser Asp 315 320 325 330 Glu Leu Lys Glu Lys Leu Glu Asp Val Leu Ile Pro Glu Gln Gln Phe 335 340 345 Thr Leu Gly Arg Met Leu Gly Lys Gly Glu Phe Gly Ser Val Arg Glu 350 355 360 Ala Gln Leu Lys Gln Glu Asp Gly Ser Phe Val Lys Val Ala Val Lys 365 370 375 Met Leu Lys Ala Asp Ile Ile Ala Ser Ser Asp Ile Glu Glu Phe Leu 380 385 390 Arg Glu Ala Ala Cys Met Lys Glu Phe Asp His Pro His Val Ala Lys 395 400 405 410 Leu Val Gly Val Ser Leu Arg Ser Arg Ala Lys Gly Arg Leu Pro Ile 415 420 425 Pro Met Val Ile Leu Pro Phe Met Lys His Gly Asp Leu His Ala Phe 430 435 440 Leu Leu Ala Ser Arg Ile Gly Glu Asn Pro Phe Asn Leu Pro Leu Gln 445 450 455 Thr Leu Ile Arg Phe Met Val Asp Ile Ala Cys Gly Met Glu Tyr Leu 460 465 470 Ser Ser Arg Asn Phe Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met 475 480 485 490 Leu Ala Glu Asp Met Thr Val Cys Val Ala Asp Phe Gly Leu Ser Arg 495 500 505 Lys Ile Tyr Ser Gly Asp Tyr Tyr Arg Gln Gly Cys Ala Ser Lys Leu 510 515 520 Pro Val Lys Trp Leu Ala Leu Glu Ser Leu Ala Asp Asn Leu Tyr Thr 525 530 535 Val Gln Ser Asp Val Trp Ala Phe Gly Val Thr Met Trp Glu Ile Met 540 545 550 Thr Arg Gly Gln Thr Pro Tyr Ala Gly Ile Glu Asn Ala Glu Ile Tyr

555 560 565 570 Asn Tyr Leu Ile Gly Gly Asn Arg Leu Lys Gln Pro Pro Glu Cys Met 575 580 585 Glu Asp Val Tyr Asp Leu Met Tyr Gln Cys Trp Ser Ala Asp Pro Lys 590 595 600 Gln Arg Pro Ser Phe Thr Cys Leu Arg Met Glu Leu Glu Asn Ile Leu 605 610 615 Gly Gln Leu Ser Val Leu Ser Ala Ser Gln Asp Pro Leu Tyr Ile Asn 620 625 630 Ile Glu Arg Ala Glu Glu Pro Thr Ala Gly Gly Ser Leu Glu Leu Pro 635 640 645 650 Gly Arg Asp Gln Pro Tyr Ser Gly Ala Gly Asp Gly Ser Gly Met Gly 655 660 665 Ala Val Gly Gly Thr Pro Ser Asp Cys Arg Tyr Ile Leu Thr Pro Gly 670 675 680 Gly Leu Ala Glu Gln Pro Gly Gln Ala Glu His Gln Pro Glu Ser Pro 685 690 695 Leu Asn Glu Thr Gln Arg Leu Leu Leu Leu Gln Gln Gly Leu Leu Pro 700 705 710 His Ser Ser Cys 715 <210> SEQ ID NO 84 <211> LENGTH: 352 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4 TM-DAP12 CER09 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 84 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Tyr Phe Leu Gly 270 275 280 Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys 285 290 295 Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln 300 305 310 Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 315 320 325 330 <210> SEQ ID NO 85 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcepsilonRIgamma transmembrane domain <400> SEQUENCE: 85 ctttgttaca ttctcgacgc gatattgttc ctttatggaa tagttttgac gctcctttat 60 tgc 63 <210> SEQ ID NO 86 <211> LENGTH: 352 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-DAP12-DAP12 CER10 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 86 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Gly Val Leu Ala Gly Ile Val Met Gly 255 260 265 Asp Leu Val Leu Thr Val Leu Ile Ala Leu Ala Val Tyr Phe Leu Gly 270 275 280 Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys 285 290 295 Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln 300 305 310 Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 315 320 325 330 <210> SEQ ID NO 87 <211> LENGTH: 722 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4-Axl CER11 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <223> OTHER INFORMATION: Tim4 signal peptide <400> SEQUENCE: 87 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120

Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys 270 275 280 Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly 285 290 295 Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr 300 305 310 Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu 315 320 325 330 Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys 335 340 345 Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn 350 355 360 Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala 365 370 375 Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys 380 385 390 Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys 395 400 405 410 Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu 415 420 425 Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe 445 450 455 Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe 460 465 470 Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met 475 480 485 490 Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr 540 545 550 Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln 555 560 565 570 Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala 575 580 585 Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe 590 595 600 Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro 605 610 615 Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met Asp Glu Gly Gly 620 625 630 Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr 635 640 645 650 Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val 655 660 665 His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro 670 675 680 Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp 685 690 695 Gly Ala 700 <210> SEQ ID NO 88 <211> LENGTH: 42 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcepsilonRIgamma signaling domain <400> SEQUENCE: 88 Arg Leu Lys Ile Gln Val Arg Lys Ala Ala Ile Thr Ser Tyr Glu Lys 1 5 10 15 Ser Asp Gly Val Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr 20 25 30 Glu Thr Leu Lys His Glu Lys Pro Pro Gln 35 40 <210> SEQ ID NO 89 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: FcepsilonRIgamma transmembrane domain <400> SEQUENCE: 89 Leu Cys Tyr Ile Leu Asp Ala Ile Leu Phe Leu Tyr Gly Ile Val Leu 1 5 10 15 Thr Leu Leu Tyr Cys 20 <210> SEQ ID NO 90 <211> LENGTH: 342 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4- FcepsilonRIgamma CER12 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 90 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp 1 5 10 15 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu 20 25 30 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 35 40 45 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 50 55 60 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 65 70 75 80 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 85 90 95 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 100 105 110 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 115 120 125 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 130 135 140 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 145 150 155 160 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 165 170 175 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 180 185 190 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 195 200 205 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 210 215 220 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 225 230 235 240 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 245 250 255 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 260 265 270 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 275 280 285 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Arg Leu Lys Ile 290 295 300 Gln Val Arg Lys Ala Ala Ile Thr Ser Tyr Glu Lys Ser Asp Gly Val 305 310 315 320 Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr Glu Thr Leu Lys 325 330 335 His Glu Lys Pro Pro Gln 340 <210> SEQ ID NO 91 <211> LENGTH: 342 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4- Fc(epsilon)RI(gamma)-Fc(epsilon)RI(gamma) CER13 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 91 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys

30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Leu Cys Tyr Ile Leu Asp Ala Ile Leu 255 260 265 Phe Leu Tyr Gly Ile Val Leu Thr Leu Leu Tyr Cys Arg Leu Lys Ile 270 275 280 Gln Val Arg Lys Ala Ala Ile Thr Ser Tyr Glu Lys Ser Asp Gly Val 285 290 295 Tyr Thr Gly Leu Ser Thr Arg Asn Gln Glu Thr Tyr Glu Thr Leu Lys 300 305 310 His Glu Lys Pro Pro Gln 315 320 <210> SEQ ID NO 92 <211> LENGTH: 86 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: NFAM1 signaling domain <400> SEQUENCE: 92 Leu Trp Asn Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg 1 5 10 15 Lys Cys Pro Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser 20 25 30 Glu Ser Val Tyr Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala 35 40 45 Cys Ile Glu Asn Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro 50 55 60 Leu Ser Gln Glu Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn 65 70 75 80 Leu Val Tyr Glu Asn Leu 85 <210> SEQ ID NO 93 <211> LENGTH: 386 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-Tim4-NFAM1 CER25 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 93 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Leu Trp Asn Lys 270 275 280 Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp 285 290 295 Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr 300 305 310 Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn 315 320 325 330 Glu Asp Gly Ser Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu 335 340 345 Arg Pro His Arg Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu 350 355 360 Asn Leu <210> SEQ ID NO 94 <211> LENGTH: 85 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BaFFR signaling domain <400> SEQUENCE: 94 Ser Trp Arg Arg Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu 1 5 10 15 Ala Pro Asp Gly Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile 20 25 30 Ile Leu Ser Pro Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro 35 40 45 Pro Gly Glu Asp Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val 50 55 60 Pro Ala Thr Glu Leu Gly Ser Thr Glu Leu Val Thr Thr Lys Thr Ala 65 70 75 80 Gly Pro Glu Gln Gln 85 <210> SEQ ID NO 95 <211> LENGTH: 540 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-BaFFR CER85 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 95 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala

175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Ser Trp Arg Arg Arg Gln Arg Arg Leu 430 435 440 Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly Asp Lys Asp Ala Pro 445 450 455 Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro Gly Ile Ser Asp Ala 460 465 470 Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp Pro Gly Thr Thr Pro 475 480 485 490 Pro Gly His Ser Val Pro Val Pro Ala Thr Glu Leu Gly Ser Thr Glu 495 500 505 Leu Val Thr Thr Lys Thr Ala Gly Pro Glu Gln Gln 510 515 <210> SEQ ID NO 96 <211> LENGTH: 507 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-Dap12 CER86 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 96 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Tyr Phe Leu Gly Arg Leu Val Pro Arg 430 435 440 Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu 445 450 455 Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr 460 465 470 Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 475 480 485 <210> SEQ ID NO 97 <211> LENGTH: 29 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD79b signaling domain <400> SEQUENCE: 97 Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly Leu Asp 1 5 10 15 Ile Asp Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu 20 25 <210> SEQ ID NO 98 <211> LENGTH: 484 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-CD79b CER89 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 98 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Asp Ser Lys Ala Gly Met Glu Glu Asp 430 435 440 His Thr Tyr Glu Gly Leu Asp Ile Asp Gln Thr Ala Thr Tyr Glu Asp 445 450 455 Ile Val Thr Leu 460 <210> SEQ ID NO 99 <211> LENGTH: 465 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated MyD88 signaling domain <400> SEQUENCE: 99 atggctgcag gaggtcccgg cgcggggtct gcggccccgg tctcctccac atcctccctt 60 cccctggctg ctctcaacat gcgagtgcgg cgccgcctgt ctctgttctt gaacgtgcgg 120 acacaggtgg cggccgactg gaccgcgctg gcggaggaga tggactttga gtacttggag 180 atccggcaac tggagacaca agcggacccc actggcaggc tgctggacgc ctggcaggga 240 cgccctggcg cctctgtagg ccgactgctc gagctgctta ccaagctggg ccgcgacgac 300 gtgctgctgg agctgggacc cagcattgag gaggattgcc aaaagtatat cttgaagcag 360 cagcaggagg aggctgagaa gcctttacag gtggccgctg tagacagcag tgtcccacgg 420 acagcagagc tggcgggcat caccacactt gatgaccccc tgggg 465 <210> SEQ ID NO 100 <211> LENGTH: 541 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-NFAM1 CER90 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 100 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Leu Trp Asn Lys Lys Arg Met Arg Gly 430 435 440 Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala Ser 445 450 455 Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr Thr Ala Leu Gln Arg 460 465 470 Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn Glu Asp Gly Ser Ser 475 480 485 490 Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu Arg Pro His Arg Phe 495 500 505 Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu Asn Leu 510 515 <210> SEQ ID NO 101 <211> LENGTH: 805 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-MerTk-CD79b CER95 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 101 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215

Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Asp Ser Lys Ala Gly Met Glu Glu 750 755 760 Asp His Thr Tyr Glu Gly Leu Asp Ile Asp Gln Thr Ala Thr Tyr Glu 765 770 775 Asp Ile Val Thr Leu 780 <210> SEQ ID NO 102 <211> LENGTH: 862 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-MerTk-NFAM1 CER96 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 102 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665

Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Leu Trp Asn Lys Lys Arg Met Arg 750 755 760 Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala 765 770 775 Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr Thr Ala Leu Gln 780 785 790 Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn Glu Asp Gly Ser 795 800 805 810 Ser Pro Thr Ala Lys Gln Ser Pro Leu Ser Gln Glu Arg Pro His Arg 815 820 825 Phe Glu Asp Asp Gly Glu Leu Asn Leu Val Tyr Glu Asn Leu 830 835 840 <210> SEQ ID NO 103 <211> LENGTH: 861 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-MERTK-BAFFR CER93 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 103 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Ser Trp Arg Arg Arg Gln Arg Arg 750 755 760 Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly Asp Lys Asp Ala 765 770 775 Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro Gly Ile Ser Asp 780 785 790 Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp Pro Gly Thr Thr 795 800 805 810 Pro Pro Gly His Ser Val Pro Val Pro Ala Thr Glu Leu Gly Ser Thr 815 820 825 Glu Leu Val Thr Thr Lys Thr Ala Gly Pro Glu Gln Gln 830 835 <210> SEQ ID NO 104 <211> LENGTH: 19 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: P2A self-cleaving peptide <400> SEQUENCE: 104 Ala Thr Asn Phe Ser Leu Leu Lys Gln Ala Gly Asp Val Glu Glu Asn 1 5 10 15 Pro Gly Pro <210> SEQ ID NO 105 <211> LENGTH: 692 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-tMyD88-P2A-Rab5a CER91 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 105 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40

Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly 270 275 280 Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu 285 290 295 Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe 300 305 310 Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu 315 320 325 330 Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala 335 340 345 Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala 350 355 360 Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp 365 370 375 Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr 380 385 390 Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala 395 400 405 410 Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr 415 420 425 Thr Leu Asp Asp Pro Leu Gly Gly Ser Gly Ala Thr Asn Phe Ser Leu 430 435 440 Leu Lys Gln Ala Gly Asp Val Glu Glu Asn Pro Gly Pro Met Ala Ser 445 450 455 Arg Gly Ala Thr Arg Pro Asn Gly Pro Asn Thr Gly Asn Lys Ile Cys 460 465 470 Gln Phe Lys Leu Val Leu Leu Gly Glu Ser Ala Val Gly Lys Ser Ser 475 480 485 490 Leu Val Leu Arg Phe Val Lys Gly Gln Phe His Glu Phe Gln Glu Ser 495 500 505 Thr Ile Gly Ala Ala Phe Leu Thr Gln Thr Val Cys Leu Asp Asp Thr 510 515 520 Thr Val Lys Phe Glu Ile Trp Asp Thr Ala Gly Gln Glu Arg Tyr His 525 530 535 Ser Leu Ala Pro Met Tyr Tyr Arg Gly Ala Gln Ala Ala Ile Val Val 540 545 550 Tyr Asp Ile Thr Asn Glu Glu Ser Phe Ala Arg Ala Lys Asn Trp Val 555 560 565 570 Lys Glu Leu Gln Arg Gln Ala Ser Pro Asn Ile Val Ile Ala Leu Ser 575 580 585 Gly Asn Lys Ala Asp Leu Ala Asn Lys Arg Ala Val Asp Phe Gln Glu 590 595 600 Ala Gln Ser Tyr Ala Asp Asp Asn Ser Leu Leu Phe Met Glu Thr Ser 605 610 615 Ala Lys Thr Ser Met Asn Val Asn Glu Ile Phe Met Ala Ile Ala Lys 620 625 630 Lys Leu Pro Lys Asn Glu Pro Gln Asn Pro Gly Ala Asn Ser Ala Arg 635 640 645 650 Gly Arg Gly Val Asp Leu Thr Glu Pro Thr Gln Pro Thr Arg Asn Gln 655 660 665 Cys Cys Ser Asn 670 <210> SEQ ID NO 106 <211> LENGTH: 264 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: mesothelin specific scFv derived from M912 antibody <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 106 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser -5 1 5 10 Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 15 20 25 Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 30 35 40 Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val 45 50 55 Pro Ser Gly Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 60 65 70 Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 75 80 85 90 Ser Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 95 100 105 Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 110 115 120 Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser 125 130 135 Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser 140 145 150 Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 155 160 165 170 Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro 175 180 185 Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln 190 195 200 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 205 210 215 Tyr Cys Ala Arg Glu Gly Lys Asn Gly Ala Phe Asp Ile Trp Gly Gln 220 225 230 Gly Thr Met Val Thr Val Ser Ser 235 240 <210> SEQ ID NO 107 <211> LENGTH: 452 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: M912 scFv-IgG4 spacer-Tim4 TM-tMyD88 CER50 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 107 Met Leu Leu Leu Val Thr Ser Leu Leu Leu Cys Glu Leu Pro His Pro -20 -15 -10 Ala Phe Leu Leu Ile Pro Asp Ile Gln Met Thr Gln Ser Pro Ser Ser -5 1 5 10 Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser 15 20 25 Gln Ser Ile Ser Ser Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys 30 35 40 Ala Pro Lys Leu Leu Ile Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val 45 50 55 Pro Ser Gly Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr 60 65 70 Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln 75 80 85 90 Ser Tyr Ser Thr Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile 95 100 105 Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly 110 115 120 Ser Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser 125 130 135 Glu Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser 140 145 150 Gly Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu 155 160 165 170 Glu Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro 175 180 185 Ser Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln 190 195 200 Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr 205 210 215 Tyr Cys Ala Arg Glu Gly Lys Asn Gly Ala Phe Asp Ile Trp Gly Gln 220 225 230 Gly Thr Met Val Thr Val Ser Ser Glu Ser Lys Tyr Gly Pro Pro Cys 235 240 245 250 Pro Pro Cys Pro Ile Leu Ile Ile Ala Cys Cys Val Gly Phe Val Leu

255 260 265 Met Val Leu Leu Phe Leu Ala Phe Leu Met Ala Ala Gly Gly Pro Gly 270 275 280 Ala Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu Pro Leu Ala 285 290 295 Ala Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe Leu Asn Val 300 305 310 Arg Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu Glu Met Asp 315 320 325 330 Phe Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala Asp Pro Thr 335 340 345 Gly Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala Ser Val Gly 350 355 360 Arg Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp Val Leu Leu 365 370 375 Glu Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr Ile Leu Lys 380 385 390 Gln Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala Ala Val Asp 395 400 405 410 Ser Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr Thr Leu Asp 415 420 425 Asp Pro Leu Gly 430 <210> SEQ ID NO 108 <400> SEQUENCE: 108 000 <210> SEQ ID NO 109 <400> SEQUENCE: 109 000 <210> SEQ ID NO 110 <400> SEQUENCE: 110 000 <210> SEQ ID NO 111 <400> SEQUENCE: 111 000 <210> SEQ ID NO 112 <400> SEQUENCE: 112 000 <210> SEQ ID NO 113 <400> SEQUENCE: 113 000 <210> SEQ ID NO 114 <211> LENGTH: 57 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 114 Lys Leu Leu Val Thr Ile His Asp Arg Arg Glu Phe Ala Lys Phe Gln 1 5 10 15 Ser Glu Arg Ser Arg Ala Arg Tyr Glu Met Ala Ser Asn Pro Leu Tyr 20 25 30 Arg Lys Pro Ile Ser Thr His Thr Val Asp Phe Thr Phe Asn Lys Phe 35 40 45 Asn Lys Ser Tyr Asn Gly Thr Val Asp 50 55 <210> SEQ ID NO 115 <211> LENGTH: 279 <212> TYPE: PRT <213> ORGANISM: Mus musculus <220> FEATURE: <223> OTHER INFORMATION: Tim4 binding domain <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 115 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr 255 <210> SEQ ID NO 116 <211> LENGTH: 829 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CER96 with truncated NFAM1 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 116 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys

350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Leu Trp Asn Lys Lys Arg Met Arg 750 755 760 Gly Pro Gly Lys Asp Pro Thr Arg Lys Cys Pro Asp Pro Arg Ser Ala 765 770 775 Ser Ser Pro Lys Gln His Pro Ser Glu Ser Val Tyr Thr Ala Leu Gln 780 785 790 Arg Arg Glu Thr Glu Val Tyr Ala Cys Ile Glu Asn Glu 795 800 805 <210> SEQ ID NO 117 <211> LENGTH: 918 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 binding domain <400> SEQUENCE: 117 Ala Ala Gly Ala Asp Ala Gly Pro Gly Pro Glu Pro Cys Ala Thr Leu 1 5 10 15 Val Gln Gly Lys Phe Phe Gly Tyr Phe Ser Ala Ala Ala Val Phe Pro 20 25 30 Ala Asn Ala Ser Arg Cys Ser Trp Thr Leu Arg Asn Pro Asp Pro Arg 35 40 45 Arg Tyr Thr Leu Tyr Met Lys Val Ala Lys Ala Pro Val Pro Cys Ser 50 55 60 Gly Pro Gly Arg Val Arg Thr Tyr Gln Phe Asp Ser Phe Leu Glu Ser 65 70 75 80 Thr Arg Thr Tyr Leu Gly Val Glu Ser Phe Asp Glu Val Leu Arg Leu 85 90 95 Cys Asp Pro Ser Ala Pro Leu Ala Phe Leu Gln Ala Ser Lys Gln Phe 100 105 110 Leu Gln Met Arg Arg Gln Gln Pro Pro Gln His Asp Gly Leu Arg Pro 115 120 125 Arg Ala Gly Pro Pro Gly Pro Thr Asp Asp Phe Ser Val Glu Tyr Leu 130 135 140 Val Val Gly Asn Arg Asn Pro Ser Arg Ala Ala Cys Gln Met Leu Cys 145 150 155 160 Arg Trp Leu Asp Ala Cys Leu Ala Gly Ser Arg Ser Ser His Pro Cys 165 170 175 Gly Ile Met Gln Thr Pro Cys Ala Cys Leu Gly Gly Glu Ala Gly Gly 180 185 190 Pro Ala Ala Gly Pro Leu Ala Pro Arg Gly Asp Val Cys Leu Arg Asp 195 200 205 Ala Val Ala Gly Gly Pro Glu Asn Cys Leu Thr Ser Leu Thr Gln Asp 210 215 220 Arg Gly Gly His Gly Ala Thr Gly Gly Trp Lys Leu Trp Ser Leu Trp 225 230 235 240 Gly Glu Cys Thr Arg Asp Cys Gly Gly Gly Leu Gln Thr Arg Thr Arg 245 250 255 Thr Cys Leu Pro Ala Pro Gly Val Glu Gly Gly Gly Cys Glu Gly Val 260 265 270 Leu Glu Glu Gly Arg Gln Cys Asn Arg Glu Ala Cys Gly Pro Ala Gly 275 280 285 Arg Thr Ser Ser Arg Ser Gln Ser Leu Arg Ser Thr Asp Ala Arg Arg 290 295 300 Arg Glu Glu Leu Gly Asp Glu Leu Gln Gln Phe Gly Phe Pro Ala Pro 305 310 315 320 Gln Thr Gly Asp Pro Ala Ala Glu Glu Trp Ser Pro Trp Ser Val Cys 325 330 335 Ser Ser Thr Cys Gly Glu Gly Trp Gln Thr Arg Thr Arg Phe Cys Val 340 345 350 Ser Ser Ser Tyr Ser Thr Gln Cys Ser Gly Pro Leu Arg Glu Gln Arg 355 360 365 Leu Cys Asn Asn Ser Ala Val Cys Pro Val His Gly Ala Trp Asp Glu 370 375 380 Trp Ser Pro Trp Ser Leu Cys Ser Ser Thr Cys Gly Arg Gly Phe Arg 385 390 395 400 Asp Arg Thr Arg Thr Cys Arg Pro Pro Gln Phe Gly Gly Asn Pro Cys 405 410 415 Glu Gly Pro Glu Lys Gln Thr Lys Phe Cys Asn Ile Ala Leu Cys Pro 420 425 430 Gly Arg Ala Val Asp Gly Asn Trp Asn Glu Trp Ser Ser Trp Ser Ala 435 440 445 Cys Ser Ala Ser Cys Ser Gln Gly Arg Gln Gln Arg Thr Arg Glu Cys 450 455 460 Asn Gly Pro Ser Tyr Gly Gly Ala Glu Cys Gln Gly His Trp Val Glu 465 470 475 480 Thr Arg Asp Cys Phe Leu Gln Gln Cys Pro Val Asp Gly Lys Trp Gln 485 490 495 Ala Trp Ala Ser Trp Gly Ser Cys Ser Val Thr Cys Gly Ala Gly Ser 500 505 510 Gln Arg Arg Glu Arg Val Cys Ser Gly Pro Phe Phe Gly Gly Ala Ala 515 520 525 Cys Gln Gly Pro Gln Asp Glu Tyr Arg Gln Cys Gly Thr Gln Arg Cys 530 535 540 Pro Glu Pro His Glu Ile Cys Asp Glu Asp Asn Phe Gly Ala Val Ile 545 550 555 560 Trp Lys Glu Thr Pro Ala Gly Glu Val Ala Ala Val Arg Cys Pro Arg 565 570 575 Asn Ala Thr Gly Leu Ile Leu Arg Arg Cys Glu Leu Asp Glu Glu Gly 580 585 590 Ile Ala Tyr Trp Glu Pro Pro Thr Tyr Ile Arg Cys Val Ser Ile Asp 595 600 605 Tyr Arg Asn Ile Gln Met Met Thr Arg Glu His Leu Ala Lys Ala Gln 610 615 620 Arg Gly Leu Pro Gly Glu Gly Val Ser Glu Val Ile Gln Thr Leu Val 625 630 635 640 Glu Ile Ser Gln Asp Gly Thr Ser Tyr Ser Gly Asp Leu Leu Ser Thr 645 650 655 Ile Asp Val Leu Arg Asn Met Thr Glu Ile Phe Arg Arg Ala Tyr Tyr 660 665 670 Ser Pro Thr Pro Gly Asp Val Gln Asn Phe Val Gln Ile Leu Ser Asn 675 680 685 Leu Leu Ala Glu Glu Asn Arg Asp Lys Trp Glu Glu Ala Gln Leu Ala 690 695 700 Gly Pro Asn Ala Lys Glu Leu Phe Arg Leu Val Glu Asp Phe Val Asp 705 710 715 720 Val Ile Gly Phe Arg Met Lys Asp Leu Arg Asp Ala Tyr Gln Val Thr 725 730 735 Asp Asn Leu Val Leu Ser Ile His Lys Leu Pro Ala Ser Gly Ala Thr 740 745 750 Asp Ile Ser Phe Pro Met Lys Gly Trp Arg Ala Thr Gly Asp Trp Ala 755 760 765 Lys Val Pro Glu Asp Arg Val Thr Val Ser Lys Ser Val Phe Ser Thr 770 775 780 Gly Leu Thr Glu Ala Asp Glu Ala Ser Val Phe Val Val Gly Thr Val 785 790 795 800 Leu Tyr Arg Asn Leu Gly Ser Phe Leu Ala Leu Gln Arg Asn Thr Thr 805 810 815 Val Leu Asn Ser Lys Val Ile Ser Val Thr Val Lys Pro Pro Pro Arg 820 825 830

Ser Leu Arg Thr Pro Leu Glu Ile Glu Phe Ala His Met Tyr Asn Gly 835 840 845 Thr Thr Asn Gln Thr Cys Ile Leu Trp Asp Glu Thr Asp Val Pro Ser 850 855 860 Ser Ser Ala Pro Pro Gln Leu Gly Pro Trp Ser Trp Arg Gly Cys Arg 865 870 875 880 Thr Val Pro Leu Asp Ala Leu Arg Thr Arg Cys Leu Cys Asp Arg Leu 885 890 895 Ser Thr Phe Ala Ile Leu Ala Gln Leu Ser Ala Asp Ala Asn Met Glu 900 905 910 Lys Ala Thr Leu Pro Ser 915 <210> SEQ ID NO 118 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 transmembrane domain <400> SEQUENCE: 118 Gly Val Val Ile Ile Val Ile Leu Leu Ile Leu Thr Gly Ala Gly Leu 1 5 10 15 Ala Ala Tyr Phe Phe 20 <210> SEQ ID NO 119 <211> LENGTH: 46 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MRC1 signaling domain <400> SEQUENCE: 119 Tyr Lys Lys Arg Arg Val His Leu Pro Gln Glu Gly Ala Phe Glu Asn 1 5 10 15 Thr Leu Tyr Phe Asn Ser Gln Ser Ser Pro Gly Thr Ser Asp Met Lys 20 25 30 Asp Leu Val Gly Asn Ile Glu Gln Asn Glu His Ser Val Ile 35 40 45 <210> SEQ ID NO 120 <211> LENGTH: 727 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ELMO <400> SEQUENCE: 120 Met Pro Pro Pro Ala Asp Ile Val Lys Val Ala Ile Glu Trp Pro Gly 1 5 10 15 Ala Tyr Pro Lys Leu Met Glu Ile Asp Gln Lys Lys Pro Leu Ser Ala 20 25 30 Ile Ile Lys Glu Val Cys Asp Gly Trp Ser Leu Ala Asn His Glu Tyr 35 40 45 Phe Ala Leu Gln His Ala Asp Ser Ser Asn Phe Tyr Ile Thr Glu Lys 50 55 60 Asn Arg Asn Glu Ile Lys Asn Gly Thr Ile Leu Arg Leu Thr Thr Ser 65 70 75 80 Pro Ala Gln Asn Ala Gln Gln Leu His Glu Arg Ile Gln Ser Ser Ser 85 90 95 Met Asp Ala Lys Leu Glu Ala Leu Lys Asp Leu Ala Ser Leu Ser Arg 100 105 110 Asp Val Thr Phe Ala Gln Glu Phe Ile Asn Leu Asp Gly Ile Ser Leu 115 120 125 Leu Thr Gln Met Val Glu Ser Gly Thr Glu Arg Tyr Gln Lys Leu Gln 130 135 140 Lys Ile Met Lys Pro Cys Phe Gly Asp Met Leu Ser Phe Thr Leu Thr 145 150 155 160 Ala Phe Val Glu Leu Met Asp His Gly Ile Val Ser Trp Asp Thr Phe 165 170 175 Ser Val Ala Phe Ile Lys Lys Ile Ala Ser Phe Val Asn Lys Ser Ala 180 185 190 Ile Asp Ile Ser Ile Leu Gln Arg Ser Leu Ala Ile Leu Glu Ser Met 195 200 205 Val Leu Asn Ser His Asp Leu Tyr Gln Lys Val Ala Gln Glu Ile Thr 210 215 220 Ile Gly Gln Leu Ile Pro His Leu Gln Gly Ser Asp Gln Glu Ile Gln 225 230 235 240 Thr Tyr Thr Ile Ala Val Ile Asn Ala Leu Phe Leu Lys Ala Pro Asp 245 250 255 Glu Arg Arg Gln Glu Met Ala Asn Ile Leu Ala Gln Lys Gln Leu Arg 260 265 270 Ser Ile Ile Leu Thr His Val Ile Arg Ala Gln Arg Ala Ile Asn Asn 275 280 285 Glu Met Ala His Gln Leu Tyr Val Leu Gln Val Leu Thr Phe Asn Leu 290 295 300 Leu Glu Asp Arg Met Met Thr Lys Met Asp Pro Gln Asp Gln Ala Gln 305 310 315 320 Arg Asp Ile Ile Phe Glu Leu Arg Arg Ile Ala Phe Asp Ala Glu Ser 325 330 335 Glu Pro Asn Asn Ser Ser Gly Ser Met Glu Lys Arg Lys Ser Met Tyr 340 345 350 Thr Arg Asp Tyr Lys Lys Leu Gly Phe Ile Asn His Val Asn Pro Ala 355 360 365 Met Asp Phe Thr Gln Thr Pro Pro Gly Met Leu Ala Leu Asp Asn Met 370 375 380 Leu Tyr Phe Ala Lys His His Gln Asp Ala Tyr Ile Arg Ile Val Leu 385 390 395 400 Glu Asn Ser Ser Arg Glu Asp Lys His Glu Cys Pro Phe Gly Arg Ser 405 410 415 Ser Ile Glu Leu Thr Lys Met Leu Cys Glu Ile Leu Lys Val Gly Glu 420 425 430 Leu Pro Ser Glu Thr Cys Asn Asp Phe His Pro Met Phe Phe Thr His 435 440 445 Asp Arg Ser Phe Glu Glu Phe Phe Cys Ile Cys Ile Gln Leu Leu Asn 450 455 460 Lys Thr Trp Lys Glu Met Arg Ala Thr Ser Glu Asp Phe Asn Lys Val 465 470 475 480 Met Gln Val Val Lys Glu Gln Val Met Arg Ala Leu Thr Thr Lys Pro 485 490 495 Ser Ser Leu Asp Gln Phe Lys Ser Lys Leu Gln Asn Leu Ser Tyr Thr 500 505 510 Glu Ile Leu Lys Ile Arg Gln Ser Glu Arg Met Asn Gln Glu Asp Phe 515 520 525 Gln Ser Arg Pro Ile Leu Glu Leu Lys Glu Lys Ile Gln Pro Glu Ile 530 535 540 Leu Glu Leu Ile Lys Gln Gln Arg Leu Asn Arg Leu Val Glu Gly Thr 545 550 555 560 Cys Phe Arg Lys Leu Asn Ala Arg Arg Arg Gln Asp Lys Phe Trp Tyr 565 570 575 Cys Arg Leu Ser Pro Asn His Lys Val Leu His Tyr Gly Asp Leu Glu 580 585 590 Glu Ser Pro Gln Gly Glu Val Pro His Asp Ser Leu Gln Asp Lys Leu 595 600 605 Pro Val Ala Asp Ile Lys Ala Val Val Thr Gly Lys Asp Cys Pro His 610 615 620 Met Lys Glu Lys Gly Ala Leu Lys Gln Asn Lys Glu Val Leu Glu Leu 625 630 635 640 Ala Phe Ser Ile Leu Tyr Asp Ser Asn Cys Gln Leu Asn Phe Ile Ala 645 650 655 Pro Asp Lys His Glu Tyr Cys Ile Trp Thr Asp Gly Leu Asn Ala Leu 660 665 670 Leu Gly Lys Asp Met Met Ser Asp Leu Thr Arg Asn Asp Leu Asp Thr 675 680 685 Leu Leu Ser Met Glu Ile Lys Leu Arg Leu Leu Asp Leu Glu Asn Ile 690 695 700 Gln Ile Pro Asp Ala Pro Pro Pro Ile Pro Lys Glu Pro Ser Asn Tyr 705 710 715 720 Asp Phe Val Tyr Asp Cys Asn 725 <210> SEQ ID NO 121 <211> LENGTH: 285 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated EGFR <400> SEQUENCE: 121 Arg Lys Val Cys Asn Gly Ile Gly Ile Gly Glu Phe Lys Asp Ser Leu 1 5 10 15 Ser Ile Asn Ala Thr Asn Ile Lys His Phe Lys Asn Cys Thr Ser Ile 20 25 30 Ser Gly Asp Leu His Ile Leu Pro Val Ala Phe Arg Gly Asp Ser Phe 35 40 45 Thr His Thr Pro Pro Leu Asp Pro Gln Glu Leu Asp Ile Leu Lys Thr 50 55 60 Val Lys Glu Ile Thr Gly Phe Leu Leu Ile Gln Ala Trp Pro Glu Asn 65 70 75 80 Arg Thr Asp Leu His Ala Phe Glu Asn Leu Glu Ile Ile Arg Gly Arg 85 90 95 Thr Lys Gln His Gly Gln Phe Ser Leu Ala Val Val Ser Leu Asn Ile 100 105 110 Thr Ser Leu Gly Leu Arg Ser Leu Lys Glu Ile Ser Asp Gly Asp Val 115 120 125 Ile Ile Ser Gly Asn Lys Asn Leu Cys Tyr Ala Asn Thr Ile Asn Trp 130 135 140 Lys Lys Leu Phe Gly Thr Ser Gly Gln Lys Thr Lys Ile Ile Ser Asn 145 150 155 160 Arg Gly Glu Asn Ser Cys Lys Ala Thr Gly Gln Val Cys His Ala Leu 165 170 175 Cys Ser Pro Glu Gly Cys Trp Gly Pro Glu Pro Arg Asp Cys Val Ser 180 185 190 Cys Arg Asn Val Ser Arg Gly Arg Glu Cys Val Asp Lys Cys Asn Leu 195 200 205

Leu Glu Gly Glu Pro Arg Glu Phe Val Glu Asn Ser Glu Cys Ile Gln 210 215 220 Cys His Pro Glu Cys Leu Pro Gln Ala Met Asn Ile Thr Cys Thr Gly 225 230 235 240 Arg Gly Pro Asp Asn Cys Ile Gln Cys Ala His Tyr Ile Asp Gly Pro 245 250 255 His Cys Val Lys Thr Cys Pro Ala Gly Val Met Gly Glu Asn Asn Thr 260 265 270 Leu Val Trp Lys Tyr Ala Asp Ala Gly His Val Cys His 275 280 285 <210> SEQ ID NO 122 <211> LENGTH: 207 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rab7 <400> SEQUENCE: 122 Met Thr Ser Arg Lys Lys Val Leu Leu Lys Val Ile Ile Leu Gly Asp 1 5 10 15 Ser Gly Val Gly Lys Thr Ser Leu Met Asn Gln Tyr Val Asn Lys Lys 20 25 30 Phe Ser Asn Gln Tyr Lys Ala Thr Ile Gly Ala Asp Phe Leu Thr Lys 35 40 45 Glu Val Met Val Asp Asp Arg Leu Val Thr Met Gln Ile Trp Asp Thr 50 55 60 Ala Gly Gln Glu Arg Phe Gln Ser Leu Gly Val Ala Phe Tyr Arg Gly 65 70 75 80 Ala Asp Cys Cys Val Leu Val Phe Asp Val Thr Ala Pro Asn Thr Phe 85 90 95 Lys Thr Leu Asp Ser Trp Arg Asp Glu Phe Leu Ile Gln Ala Ser Pro 100 105 110 Arg Asp Pro Glu Asn Phe Pro Phe Val Val Leu Gly Asn Lys Ile Asp 115 120 125 Leu Glu Asn Arg Gln Val Ala Thr Lys Arg Ala Gln Ala Trp Cys Tyr 130 135 140 Ser Lys Asn Asn Ile Pro Tyr Phe Glu Thr Ser Ala Lys Glu Ala Ile 145 150 155 160 Asn Val Glu Gln Ala Phe Gln Thr Ile Ala Arg Asn Ala Leu Lys Gln 165 170 175 Glu Thr Glu Val Glu Leu Tyr Asn Glu Phe Pro Glu Pro Ile Lys Leu 180 185 190 Asp Lys Asn Asp Arg Ala Lys Ala Ser Ala Glu Ser Cys Ser Cys 195 200 205 <210> SEQ ID NO 123 <211> LENGTH: 184 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Rap1A <400> SEQUENCE: 123 Met Arg Glu Tyr Lys Leu Val Val Leu Gly Ser Gly Gly Val Gly Lys 1 5 10 15 Ser Ala Leu Thr Val Gln Phe Val Gln Gly Ile Phe Val Glu Lys Tyr 20 25 30 Asp Pro Thr Ile Glu Asp Ser Tyr Arg Lys Gln Val Glu Val Asp Cys 35 40 45 Gln Gln Cys Met Leu Glu Ile Leu Asp Thr Ala Gly Thr Glu Gln Phe 50 55 60 Thr Ala Met Arg Asp Leu Tyr Met Lys Asn Gly Gln Gly Phe Ala Leu 65 70 75 80 Val Tyr Ser Ile Thr Ala Gln Ser Thr Phe Asn Asp Leu Gln Asp Leu 85 90 95 Arg Glu Gln Ile Leu Arg Val Lys Asp Thr Glu Asp Val Pro Met Ile 100 105 110 Leu Val Gly Asn Lys Cys Asp Leu Glu Asp Glu Arg Val Val Gly Lys 115 120 125 Glu Gln Gly Gln Asn Leu Ala Arg Gln Trp Cys Asn Cys Ala Phe Leu 130 135 140 Glu Ser Ser Ala Lys Ser Lys Ile Asn Val Asn Glu Ile Phe Tyr Asp 145 150 155 160 Leu Val Arg Gln Ile Asn Arg Lys Thr Pro Val Glu Lys Lys Lys Pro 165 170 175 Lys Lys Lys Ser Cys Leu Leu Leu 180 <210> SEQ ID NO 124 <211> LENGTH: 193 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: RhoA <400> SEQUENCE: 124 Met Ala Ala Ile Arg Lys Lys Leu Val Ile Val Gly Asp Gly Ala Cys 1 5 10 15 Gly Lys Thr Cys Leu Leu Ile Val Phe Ser Lys Asp Gln Phe Pro Glu 20 25 30 Val Tyr Val Pro Thr Val Phe Glu Asn Tyr Val Ala Asp Ile Glu Val 35 40 45 Asp Gly Lys Gln Val Glu Leu Ala Leu Trp Asp Thr Ala Gly Gln Glu 50 55 60 Asp Tyr Asp Arg Leu Arg Pro Leu Ser Tyr Pro Asp Thr Asp Val Ile 65 70 75 80 Leu Met Cys Phe Ser Ile Asp Ser Pro Asp Ser Leu Glu Asn Ile Pro 85 90 95 Glu Lys Trp Thr Pro Glu Val Lys His Phe Cys Pro Asn Val Pro Ile 100 105 110 Ile Leu Val Gly Asn Lys Lys Asp Leu Arg Asn Asp Glu His Thr Arg 115 120 125 Arg Glu Leu Ala Lys Met Lys Gln Glu Pro Val Lys Pro Glu Glu Gly 130 135 140 Arg Asp Met Ala Asn Arg Ile Gly Ala Phe Gly Tyr Met Glu Cys Ser 145 150 155 160 Ala Lys Thr Lys Asp Gly Val Arg Glu Val Phe Glu Met Ala Thr Arg 165 170 175 Ala Ala Leu Gln Ala Arg Arg Gly Lys Lys Lys Ser Gly Cys Leu Val 180 185 190 Leu <210> SEQ ID NO 125 <211> LENGTH: 191 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CDC42 <400> SEQUENCE: 125 Met Gln Thr Ile Lys Cys Val Val Val Gly Asp Gly Ala Val Gly Lys 1 5 10 15 Thr Cys Leu Leu Ile Ser Tyr Thr Thr Asn Lys Phe Pro Ser Glu Tyr 20 25 30 Val Pro Thr Val Phe Asp Asn Tyr Ala Val Thr Val Met Ile Gly Gly 35 40 45 Glu Pro Tyr Thr Leu Gly Leu Phe Asp Thr Ala Gly Gln Glu Asp Tyr 50 55 60 Asp Arg Leu Arg Pro Leu Ser Tyr Pro Gln Thr Asp Val Phe Leu Val 65 70 75 80 Cys Phe Ser Val Val Ser Pro Ser Ser Phe Glu Asn Val Lys Glu Lys 85 90 95 Trp Val Pro Glu Ile Thr His His Cys Pro Lys Thr Pro Phe Leu Leu 100 105 110 Val Gly Thr Gln Ile Asp Leu Arg Asp Asp Pro Ser Thr Ile Glu Lys 115 120 125 Leu Ala Lys Asn Lys Gln Lys Pro Ile Thr Pro Glu Thr Ala Glu Lys 130 135 140 Leu Ala Arg Asp Leu Lys Ala Val Lys Tyr Val Glu Cys Ser Ala Leu 145 150 155 160 Thr Gln Lys Gly Leu Lys Asn Val Phe Asp Glu Ala Ile Leu Ala Ala 165 170 175 Leu Glu Pro Pro Glu Pro Lys Lys Ser Arg Arg Cys Val Leu Leu 180 185 190 <210> SEQ ID NO 126 <211> LENGTH: 255 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAFFR signaling domain <400> SEQUENCE: 126 tcctggagac ggcgacaaag gcgcttgcgc ggcgcatcat ccgcagaggc gcccgacggc 60 gataaggacg cgcccgaacc ccttgataaa gttattatct tgtcaccggg aatttctgac 120 gctacggcac ccgcgtggcc tcctccgggc gaagatcctg gtacgacacc ccctggacac 180 agtgttcccg tgcccgcgac agagctcggt agcacagaac tggtgaccac aaagacggcg 240 ggaccggaac agcaa 255 <210> SEQ ID NO 127 <211> LENGTH: 156 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: DAP12 signaling domain <400> SEQUENCE: 127 tattttctgg gaaggctcgt tcctagaggt agaggtgctg ccgaagcagc gacgcgcaaa 60 cagaggatta ctgaaacgga gtctccctac caagagctgc aaggccagag gtcagatgtc 120 tattcagact tgaacacaca aaggccatac tacaaa 156 <210> SEQ ID NO 128 <211> LENGTH: 135 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD79b signaling domain <400> SEQUENCE: 128 gacagtaaag ccgggatgga agaggaccac acatacgagg ggcttgacat agatcaaaca 60

gcgacatacg aagacatcgt aaccttgcgg actggagagg ttaaatggtc agtcggagaa 120 caccccggcc aagaa 135 <210> SEQ ID NO 129 <211> LENGTH: 258 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: NFAM1 signaling domain <400> SEQUENCE: 129 ctctggaata aaaagaggat gcgcggcccg ggaaaagacc caacgagaaa gtgtcccgat 60 ccccgcagtg cgtcaagccc caagcagcat ccttccgaaa gcgtatatac ggcacttcaa 120 cgccgggaaa cggaggtata tgcgtgtatt gagaacgagg acgggtcatc cccgaccgcc 180 aaacagtccc ctctcagcca agagcgacct cacaggtttg aggacgatgg tgaactcaat 240 ctggtctacg aaaacctg 258 <210> SEQ ID NO 130 <211> LENGTH: 540 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-BAFFR-tMyD88 CER87 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 130 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ser Trp Arg Arg 270 275 280 Arg Gln Arg Arg Leu Arg Gly Ala Ser Ser Ala Glu Ala Pro Asp Gly 285 290 295 Asp Lys Asp Ala Pro Glu Pro Leu Asp Lys Val Ile Ile Leu Ser Pro 300 305 310 Gly Ile Ser Asp Ala Thr Ala Pro Ala Trp Pro Pro Pro Gly Glu Asp 315 320 325 330 Pro Gly Thr Thr Pro Pro Gly His Ser Val Pro Val Pro Ala Thr Glu 335 340 345 Leu Gly Ser Thr Glu Leu Val Thr Thr Lys Thr Ala Gly Pro Glu Gln 350 355 360 Gln Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser 365 370 375 Ser Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg 380 385 390 Arg Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp 395 400 405 410 Thr Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln 415 420 425 Leu Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln 430 435 440 Gly Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys 445 450 455 Leu Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu 460 465 470 Asp Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys 475 480 485 490 Pro Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu 495 500 505 Leu Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly 510 515 <210> SEQ ID NO 131 <211> LENGTH: 507 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: Tim4-DAP12-tMyD88 CER88 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 131 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Tyr Phe Leu Gly 270 275 280 Arg Leu Val Pro Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys 285 290 295 Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln 300 305 310 Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 315 320 325 330 Met Ala Ala Gly Gly Pro Gly Ala Gly Ser Ala Ala Pro Val Ser Ser 335 340 345 Thr Ser Ser Leu Pro Leu Ala Ala Leu Asn Met Arg Val Arg Arg Arg 350 355 360 Leu Ser Leu Phe Leu Asn Val Arg Thr Gln Val Ala Ala Asp Trp Thr 365 370 375 Ala Leu Ala Glu Glu Met Asp Phe Glu Tyr Leu Glu Ile Arg Gln Leu 380 385 390 Glu Thr Gln Ala Asp Pro Thr Gly Arg Leu Leu Asp Ala Trp Gln Gly 395 400 405 410 Arg Pro Gly Ala Ser Val Gly Arg Leu Leu Glu Leu Leu Thr Lys Leu 415 420 425 Gly Arg Asp Asp Val Leu Leu Glu Leu Gly Pro Ser Ile Glu Glu Asp 430 435 440 Cys Gln Lys Tyr Ile Leu Lys Gln Gln Gln Glu Glu Ala Glu Lys Pro 445 450 455 Leu Gln Val Ala Ala Val Asp Ser Ser Val Pro Arg Thr Ala Glu Leu 460 465 470 Ala Gly Ile Thr Thr Leu Asp Asp Pro Leu Gly

475 480 485 <210> SEQ ID NO 132 <211> LENGTH: 53 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: truncated NFAM1 signaling domain <400> SEQUENCE: 132 Leu Trp Asn Lys Lys Arg Met Arg Gly Pro Gly Lys Asp Pro Thr Arg 1 5 10 15 Lys Cys Pro Asp Pro Arg Ser Ala Ser Ser Pro Lys Gln His Pro Ser 20 25 30 Glu Ser Val Tyr Thr Ala Leu Gln Arg Arg Glu Thr Glu Val Tyr Ala 35 40 45 Cys Ile Glu Asn Glu 50 <210> SEQ ID NO 133 <211> LENGTH: 931 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TIM4-MERTK-tMYD88 CER92 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 133 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Met Ala Ala Gly Gly Pro Gly Ala 750 755 760 Gly Ser Ala Ala Pro Val Ser Ser Thr Ser Ser Leu Pro Leu Ala Ala 765 770 775 Leu Asn Met Arg Val Arg Arg Arg Leu Ser Leu Phe Leu Asn Val Arg 780 785 790 Thr Gln Val Ala Ala Asp Trp Thr Ala Leu Ala Glu Glu Met Asp Phe 795 800 805 810 Glu Tyr Leu Glu Ile Arg Gln Leu Glu Thr Gln Ala Asp Pro Thr Gly 815 820 825 Arg Leu Leu Asp Ala Trp Gln Gly Arg Pro Gly Ala Ser Val Gly Arg 830 835 840 Leu Leu Glu Leu Leu Thr Lys Leu Gly Arg Asp Asp Val Leu Leu Glu 845 850 855 Leu Gly Pro Ser Ile Glu Glu Asp Cys Gln Lys Tyr Ile Leu Lys Gln 860 865 870 Gln Gln Glu Glu Ala Glu Lys Pro Leu Gln Val Ala Ala Val Asp Ser 875 880 885 890 Ser Val Pro Arg Thr Ala Glu Leu Ala Gly Ile Thr Thr Leu Asp Asp 895 900 905 Pro Leu Gly <210> SEQ ID NO 134 <211> LENGTH: 828 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: TIM4-MERTK-DAP12 CER94 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 134 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105

Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu Ala Leu Arg Arg 270 275 280 Arg Val Gln Glu Thr Lys Phe Gly Gly Ala Phe Ser Glu Glu Asp Ser 285 290 295 Gln Leu Val Val Asn Tyr Arg Ala Lys Lys Ser Phe Cys Arg Arg Ala 300 305 310 Ile Glu Leu Thr Leu Gln Ser Leu Gly Val Ser Glu Glu Leu Gln Asn 315 320 325 330 Lys Leu Glu Asp Val Val Ile Asp Arg Asn Leu Leu Val Leu Gly Lys 335 340 345 Val Leu Gly Glu Gly Glu Phe Gly Ser Val Met Glu Gly Asn Leu Lys 350 355 360 Gln Glu Asp Gly Thr Ser Gln Lys Val Ala Val Lys Thr Met Lys Leu 365 370 375 Asp Asn Phe Ser Gln Arg Glu Ile Glu Glu Phe Leu Ser Glu Ala Ala 380 385 390 Cys Met Lys Asp Phe Asn His Pro Asn Val Ile Arg Leu Leu Gly Val 395 400 405 410 Cys Ile Glu Leu Ser Ser Gln Gly Ile Pro Lys Pro Met Val Ile Leu 415 420 425 Pro Phe Met Lys Tyr Gly Asp Leu His Thr Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Asn Thr Gly Pro Lys Tyr Ile His Leu Gln Thr Leu Leu Lys Phe 445 450 455 Met Met Asp Ile Ala Gln Gly Met Glu Tyr Leu Ser Asn Arg Asn Phe 460 465 470 Leu His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Arg Asp Asp Met 475 480 485 490 Thr Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Ser Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ala Phe Gly Val Thr Met Trp Glu Ile Thr Thr Arg Gly Met Thr 540 545 550 Pro Tyr Pro Gly Val Gln Asn His Glu Met Tyr Asp Tyr Leu Leu His 555 560 565 570 Gly His Arg Leu Lys Gln Pro Glu Asp Cys Leu Asp Glu Leu Tyr Asp 575 580 585 Ile Met Tyr Ser Cys Trp Ser Ala Asp Pro Leu Asp Arg Pro Thr Phe 590 595 600 Ser Val Leu Arg Leu Gln Leu Glu Lys Leu Ser Glu Ser Leu Pro Asp 605 610 615 Ala Gln Asp Lys Glu Ser Ile Ile Tyr Ile Asn Thr Gln Leu Leu Glu 620 625 630 Ser Cys Glu Gly Ile Ala Asn Gly Pro Ser Leu Thr Gly Leu Asp Met 635 640 645 650 Asn Ile Asp Pro Asp Ser Ile Ile Ala Ser Cys Thr Pro Gly Ala Ala 655 660 665 Val Ser Val Val Thr Ala Glu Val His Glu Asn Asn Leu Arg Glu Glu 670 675 680 Arg Tyr Ile Leu Asn Gly Gly Asn Glu Glu Trp Glu Asp Val Ser Ser 685 690 695 Thr Pro Phe Ala Ala Val Thr Pro Glu Lys Asp Gly Val Leu Pro Glu 700 705 710 Asp Arg Leu Thr Lys Asn Gly Val Ser Trp Ser His His Ser Thr Leu 715 720 725 730 Pro Leu Gly Ser Pro Ser Pro Asp Glu Leu Leu Phe Val Asp Asp Ser 735 740 745 Leu Glu Asp Ser Glu Val Leu Met Tyr Phe Leu Gly Arg Leu Val Pro 750 755 760 Arg Gly Arg Gly Ala Ala Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr 765 770 775 Glu Thr Glu Ser Pro Tyr Gln Glu Leu Gln Gly Gln Arg Ser Asp Val 780 785 790 Tyr Ser Asp Leu Asn Thr Gln Arg Pro Tyr Tyr Lys 795 800 805 <210> SEQ ID NO 135 <211> LENGTH: 2754 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 binding domain <400> SEQUENCE: 135 gccgccggag cagacgcggg gcccgggccc gagccgtgcg ccacgctggt gcagggaaag 60 ttcttcggct acttctccgc ggccgccgtg ttcccggcca acgcctcgcg ctgctcctgg 120 acgctacgca acccggaccc gcggcgctac actctctaca tgaaggtggc caaggcgccc 180 gtgccctgca gcggccccgg ccgcgtgcgc acctaccagt tcgactcctt cctcgagtcc 240 acgcgcacct acctgggcgt ggagagcttc gacgaggtgc tgcggctctg cgacccctcc 300 gcacccctgg ccttcctgca ggccagcaag cagttcctgc agatgcggcg ccagcagccg 360 ccccagcacg acgggctccg gccccgggcc gggccgccgg gccccaccga cgacttctcc 420 gtggagtacc tggtggtggg gaaccgcaac cccagccgtg ccgcctgcca gatgctgtgc 480 cgctggctgg acgcgtgtct ggccggtagt cgcagctcgc acccctgcgg gatcatgcag 540 accccctgcg cctgcctggg cggcgaggcg ggcggccctg ccgcgggacc cctggccccc 600 cgcggggatg tctgcttgag agatgcggtg gctggtggcc ctgaaaactg cctcaccagc 660 ctgacccagg accggggcgg gcacggcgcc acaggcggct ggaagctgtg gtccctgtgg 720 ggcgaatgca cgcgggactg cgggggaggc ctccagacgc ggacgcgcac ctgcctgccc 780 gcgccgggcg tggagggcgg cggctgcgag ggggtgctgg aggagggtcg ccagtgcaac 840 cgcgaggcct gcggccccgc tgggcgcacc agctcccgga gccagtccct gcggtccaca 900 gatgcccggc ggcgcgagga gctgggggac gagctgcagc agtttgggtt cccagccccc 960 cagaccggtg acccagcagc cgaggagtgg tccccgtgga gcgtgtgctc cagcacctgc 1020 ggcgagggct ggcagacccg cacgcgcttc tgcgtgtcct cctcctacag cacgcagtgc 1080 agcggacccc tgcgcgagca gcggctgtgc aacaactctg ccgtgtgccc agtgcatggt 1140 gcctgggatg agtggtcgcc ctggagcctc tgctccagca cctgtggccg tggctttcgg 1200 gatcgcacgc gcacctgcag gcccccccag tttgggggca acccctgtga gggccctgag 1260 aagcaaacca agttctgcaa cattgccctg tgccctggcc gggcagtgga tggaaactgg 1320 aatgagtggt cgagctggag cgcctgctcc gccagctgct cccagggccg acagcagcgc 1380 acgcgtgaat gcaacgggcc ttcctacggg ggtgcggagt gccagggcca ctgggtggag 1440 acccgagact gcttcctgca gcagtgccca gtggatggca agtggcaggc ctgggcgtca 1500 tggggcagtt gcagcgtcac gtgtggggct ggcagccagc gacgggagcg tgtctgctct 1560 gggcccttct tcgggggagc agcctgccag ggcccccagg atgagtaccg gcagtgcggc 1620 acccagcggt gtcccgagcc ccatgagatc tgtgatgagg acaactttgg tgctgtgatc 1680 tggaaggaga ccccagcggg agaggtggct gctgtccggt gtccccgcaa cgccacagga 1740 ctcatcctgc gacggtgtga gctggacgag gaaggcatcg cctactggga gccccccacc 1800 tacatccgct gtgtttccat tgactacaga aacatccaga tgatgacccg ggagcacctg 1860 gccaaggctc agcgagggct gcctggggag ggggtctcgg aggtcatcca gacactggtg 1920 gagatctctc aggacgggac cagctacagt ggggacctgc tgtccaccat cgatgtcctg 1980 aggaacatga cagagatttt ccggagagcg tactacagcc ccacccctgg ggacgtacag 2040 aactttgtcc agatccttag caacctgttg gcagaggaga atcgggacaa gtgggaggag 2100 gcccagctgg cgggccccaa cgccaaggag ctgttccggc tggtggagga ctttgtggac 2160 gtcatcggct tccgcatgaa ggacctgagg gatgcatacc aggtgacaga caacctggtt 2220 ctcagcatcc ataagctccc agccagcgga gccactgaca tcagcttccc catgaagggc 2280 tggcgggcca cgggtgactg ggccaaggtg ccagaggaca gggtcactgt gtccaagagt 2340 gtcttctcca cggggctgac agaggccgat gaagcatccg tgtttgtggt gggcaccgtg 2400 ctctacagga acctgggcag cttcctggcc ctgcagagga acacgaccgt cctgaattct 2460 aaggtgatct ccgtgactgt gaaacccccg cctcgctccc tgcgcacacc cttggagatc 2520 gagtttgccc acatgtataa tggcaccacc aaccagacct gtatcctgtg ggatgagacg 2580 gatgtaccct cctcctccgc ccccccgcag ctcgggccct ggtcgtggcg cggctgccgc 2640 acggtgcccc tcgacgccct ccggacgcgc tgcctctgtg accggctctc caccttcgcc 2700 atcttagccc agctcagcgc cgacgcgaac atggagaagg cgactctgcc gtcg 2754 <210> SEQ ID NO 136 <211> LENGTH: 397 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 signaling domain <400> SEQUENCE: 136 Arg Arg Glu Val Gln Asp Ala Val Lys Cys Arg Val Val Asp Arg Gln 1 5 10 15 Glu Glu Gly Asn Gly Asp Ser Gly Gly Ser Phe Gln Asn Gly His Ala 20 25 30

Gln Leu Met Thr Asp Phe Glu Lys Asp Val Asp Leu Ala Cys Arg Ser 35 40 45 Val Leu Asn Lys Asp Ile Ala Ala Cys Arg Thr Ala Thr Ile Thr Gly 50 55 60 Thr Leu Lys Arg Pro Ser Leu Pro Glu Glu Glu Lys Leu Lys Leu Ala 65 70 75 80 His Ala Lys Gly Pro Pro Thr Asn Phe Asn Ser Leu Pro Ala Asn Val 85 90 95 Ser Lys Leu His Leu His Gly Ser Pro Arg Tyr Pro Gly Gly Pro Leu 100 105 110 Pro Asp Phe Pro Asn His Ser Leu Thr Leu Lys Arg Asp Lys Ala Pro 115 120 125 Lys Ser Ser Phe Val Gly Asp Gly Asp Ile Phe Lys Lys Leu Asp Ser 130 135 140 Glu Leu Ser Arg Ala Gln Glu Lys Ala Leu Asp Thr Ser Tyr Val Ile 145 150 155 160 Leu Pro Thr Ala Thr Ala Thr Leu Arg Pro Lys Pro Lys Glu Glu Pro 165 170 175 Lys Tyr Ser Ile His Ile Asp Gln Met Pro Gln Thr Arg Leu Ile His 180 185 190 Leu Ser Thr Ala Pro Glu Ala Ser Leu Pro Ala Arg Ser Pro Pro Ser 195 200 205 Arg Gln Pro Pro Ser Gly Gly Pro Pro Glu Ala Pro Pro Ala Gln Pro 210 215 220 Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Pro Gln Gln Pro Leu Pro 225 230 235 240 Pro Pro Pro Asn Leu Glu Pro Ala Pro Pro Ser Leu Gly Asp Pro Gly 245 250 255 Glu Pro Ala Ala His Pro Gly Pro Ser Thr Gly Pro Ser Thr Lys Asn 260 265 270 Glu Asn Val Ala Thr Leu Ser Val Ser Ser Leu Glu Arg Arg Lys Ser 275 280 285 Arg Tyr Ala Glu Leu Asp Phe Glu Lys Ile Met His Thr Arg Lys Arg 290 295 300 His Gln Asp Met Phe Gln Asp Leu Asn Arg Lys Leu Gln His Ala Ala 305 310 315 320 Glu Lys Asp Lys Glu Val Leu Gly Pro Asp Ser Lys Pro Glu Lys Gln 325 330 335 Gln Thr Pro Asn Lys Arg Pro Trp Glu Ser Leu Arg Lys Ala His Gly 340 345 350 Thr Pro Thr Trp Val Lys Lys Glu Leu Glu Pro Leu Gln Pro Ser Pro 355 360 365 Leu Glu Leu Arg Ser Val Glu Trp Glu Arg Ser Gly Ala Thr Ile Pro 370 375 380 Leu Val Gly Gln Asp Ile Ile Asp Leu Gln Thr Glu Val 385 390 395 <210> SEQ ID NO 137 <211> LENGTH: 171 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ItgB5 signaling domain <400> SEQUENCE: 137 aagctgcttg tcaccatcca cgaccggagg gagtttgcaa agtttcagag cgagcgatcc 60 agggcccgct atgaaatggc ttcaaatcca ttatacagaa agcctatctc cacgcacact 120 gtggacttca ccttcaacaa gttcaacaaa tcctacaatg gcactgtgga c 171 <210> SEQ ID NO 138 <211> LENGTH: 1419 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: MERTK signaling domain <400> SEQUENCE: 138 aaaagagtcc aggagacaaa gtttgggaat gcattcacag aggaggattc tgaattagtg 60 gtgaattata tagcaaagaa atccttctgt cggcgagcca ttgaacttac cttacatagc 120 ttgggagtca gtgaggaact acaaaataaa ctagaagatg ttgtgattga caggaatctt 180 ctaattcttg gaaaaattct gggtgaagga gagtttgggt ctgtaatgga aggaaatctt 240 aagcaggaag atgggacctc tctgaaagtg gcagtgaaga ccatgaagtt ggacaactct 300 tcacagcggg agatcgagga gtttctcagt gaggcagcgt gcatgaaaga cttcagccac 360 ccaaatgtca ttcgacttct aggtgtgtgt atagaaatga gctctcaagg catcccaaag 420 cccatggtaa ttttaccctt catgaaatac ggggacctgc atacttactt actttattcc 480 cgattggaga caggaccaaa gcatattcct ctgcagacac tattgaagtt catggtggat 540 attgccctgg gaatggagta tctgagcaac aggaattttc ttcatcgaga tttagctgct 600 cgaaactgca tgttgcgaga tgacatgact gtctgtgttg cggacttcgg cctctctaag 660 aagatttaca gtggcgatta ttaccgccaa ggccgcattg ctaagatgcc tgttaaatgg 720 atcgccatag aaagtcttgc agaccgagtc tacacaagta aaagtgatgt gtgggcattt 780 ggcgtgacca tgtgggaaat agctacgcgg ggaatgactc cctatcctgg ggtccagaac 840 catgagatgt atgactatct tctccatggc cacaggttga agcagcccga agactgcctg 900 gatgaactgt atgaaataat gtactcttgc tggagaaccg atcccttaga ccgccccacc 960 ttttcagtat tgaggctgca gctagaaaaa ctcttagaaa gtttgcctga cgttcggaac 1020 caagcagacg ttatttacgt caatacacag ttgctggaga gctctgaggg cctggcccag 1080 ggctccaccc ttgctccact ggacttgaac atcgaccctg actctataat tgcctcctgc 1140 actccccgcg ctgccatcag tgtggtcaca gcagaagttc atgacagcaa acctcatgaa 1200 ggacggtaca tcctgaatgg gggcagtgag gaatgggaag atctgacttc tgccccctct 1260 gctgcagtca cagctgaaaa gaacagtgtt ttaccggggg agagacttgt taggaatggg 1320 gtctcctggt cccattcgag catgctgccc ttgggaagct cattgcccga tgaacttttg 1380 tttgctgacg actcctcaga aggctcagaa gtcctgatg 1419 <210> SEQ ID NO 139 <211> LENGTH: 1191 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 signaling domain <400> SEQUENCE: 139 cgtagagagg tccaggacgc tgtgaaatgc cgtgtggttg accggcagga ggagggcaac 60 ggggactcag ggggctcctt ccagaacggc cacgcccagc tcatgaccga cttcgagaag 120 gacgtggatc tggcctgtag atcagtgctg aacaaggaca tcgcggcctg ccgcactgcc 180 accatcacgg gcacactgaa gcggccgtct ctgcccgagg aggagaagct gaagctggcc 240 catgccaagg ggccgcccac caatttcaac agcctgccgg ccaacgtgtc caagctgcac 300 ctgcacggct caccccgcta tcccggcggg cccctgcccg acttccccaa ccactcactg 360 accctcaaga gggacaaggc gcccaagtcc tccttcgtcg gtgacgggga catcttcaag 420 aagctggact cggagctgag ccgggcccag gagaaggctc tggacacgag ctacgtgatc 480 ctgcccacgg ccacggccac gctgcggccc aagcccaagg aggagcccaa gtacagcatc 540 cacattgacc agatgccgca gacccgcctc atccacctca gcacggcccc cgaggccagc 600 ctccccgccc gcagcccgcc ctcccgccag ccccccagcg gcgggccccc cgaggcaccc 660 cctgcccagc ccccaccgcc tccgccccca ccgccaccac ctccccagca gcccctgccc 720 ccaccgccca atctggagcc ggcacccccc agcctggggg atcccgggga gcctgccgcc 780 catccgggac ccagcacggg gcccagcacc aagaacgaga atgtcgccac cttgtctgtg 840 agctccctgg agcggcggaa gtcgcggtat gcagaactgg actttgagaa gatcatgcac 900 acccggaagc ggcaccaaga catgttccag gacctgaacc ggaagctgca gcacgcagcg 960 gagaaggaca aggaggtgct ggggccggac agcaagccgg aaaagcagca gacgcccaac 1020 aagaggccct gggagagcct ccggaaagcc cacgggacgc ccacgtgggt gaagaaggag 1080 ctggagccgc tgcagccgtc gccgctggag cttcgcagcg tggagtggga gaggtcgggc 1140 gccacgatcc cgctggtggg ccaggacatc atcgacctcc agaccgaggt c 1191 <210> SEQ ID NO 140 <211> LENGTH: 1191 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: ELMO <400> SEQUENCE: 140 cgtagagagg tccaggacgc tgtgaaatgc cgtgtggttg accggcagga ggagggcaac 60 ggggactcag ggggctcctt ccagaacggc cacgcccagc tcatgaccga cttcgagaag 120 gacgtggatc tggcctgtag atcagtgctg aacaaggaca tcgcggcctg ccgcactgcc 180 accatcacgg gcacactgaa gcggccgtct ctgcccgagg aggagaagct gaagctggcc 240 catgccaagg ggccgcccac caatttcaac agcctgccgg ccaacgtgtc caagctgcac 300 ctgcacggct caccccgcta tcccggcggg cccctgcccg acttccccaa ccactcactg 360 accctcaaga gggacaaggc gcccaagtcc tccttcgtcg gtgacgggga catcttcaag 420 aagctggact cggagctgag ccgggcccag gagaaggctc tggacacgag ctacgtgatc 480 ctgcccacgg ccacggccac gctgcggccc aagcccaagg aggagcccaa gtacagcatc 540 cacattgacc agatgccgca gacccgcctc atccacctca gcacggcccc cgaggccagc 600 ctccccgccc gcagcccgcc ctcccgccag ccccccagcg gcgggccccc cgaggcaccc 660 cctgcccagc ccccaccgcc tccgccccca ccgccaccac ctccccagca gcccctgccc 720 ccaccgccca atctggagcc ggcacccccc agcctggggg atcccgggga gcctgccgcc 780 catccgggac ccagcacggg gcccagcacc aagaacgaga atgtcgccac cttgtctgtg 840 agctccctgg agcggcggaa gtcgcggtat gcagaactgg actttgagaa gatcatgcac 900 acccggaagc ggcaccaaga catgttccag gacctgaacc ggaagctgca gcacgcagcg 960 gagaaggaca aggaggtgct ggggccggac agcaagccgg aaaagcagca gacgcccaac 1020 aagaggccct gggagagcct ccggaaagcc cacgggacgc ccacgtgggt gaagaaggag 1080 ctggagccgc tgcagccgtc gccgctggag cttcgcagcg tggagtggga gaggtcgggc 1140 gccacgatcc cgctggtggg ccaggacatc atcgacctcc agaccgaggt c 1191 <210> SEQ ID NO 141 <211> LENGTH: 126 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: Fc(epsilon) RI(gamma) signaling domain

<400> SEQUENCE: 141 cgactgaaga tccaagtgcg aaaggcagct ataaccagct atgagaaatc agatggtgtt 60 tacacgggcc tgagcaccag gaaccaggag acttacgaga ctctgaagca tgagaaacca 120 ccacag 126 <210> SEQ ID NO 142 <211> LENGTH: 21 <212> TYPE: PRT <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 transmembrane domain <400> SEQUENCE: 142 Val Thr Leu Ile Val Gly Cys Gly Val Ser Ser Leu Thr Leu Leu Met 1 5 10 15 Leu Val Ile Ile Tyr 20 <210> SEQ ID NO 143 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: BAI1 transmembrane domain <400> SEQUENCE: 143 gtgacgctca tcgtgggctg tggcgtgtcc tctctcaccc tgctcatgct ggtcatcatc 60 tac 63 <210> SEQ ID NO 144 <211> LENGTH: 81 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: CD28 transmembrane domain <400> SEQUENCE: 144 ttttgggtgc tggtggtggt tggtggagtc ctggcttgct atagcttgct agtaacagtg 60 gcctttatta ttttctgggt g 81 <210> SEQ ID NO 145 <211> LENGTH: 63 <212> TYPE: DNA <213> ORGANISM: Homo sapiens <220> FEATURE: <223> OTHER INFORMATION: DAP12 transmembrane domain <400> SEQUENCE: 145 ggcgtgctgg cagggatcgt gatgggagac ctggtgctga cagtgctcat tgccctggcc 60 gtg 63 <210> SEQ ID NO 146 <400> SEQUENCE: 146 000 <210> SEQ ID NO 147 <211> LENGTH: 18 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: T2A self-cleaving peptide <400> SEQUENCE: 147 Glu Gly Arg Gly Ser Leu Leu Thr Cys Gly Asp Val Glu Glu Asn Pro 1 5 10 15 Gly Pro <210> SEQ ID NO 148 <211> LENGTH: 20 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: E2A self-cleaving peptide <400> SEQUENCE: 148 Gln Cys Thr Asn Tyr Ala Leu Leu Lys Leu Ala Gly Asp Val Glu Ser 1 5 10 15 Asn Pro Gly Pro 20 <210> SEQ ID NO 149 <211> LENGTH: 22 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: F2A self-cleaving peptide <400> SEQUENCE: 149 Val Lys Gln Thr Leu Asn Phe Asp Leu Leu Lys Leu Ala Gly Asp Val 1 5 10 15 Glu Ser Asn Pro Gly Pro 20 <210> SEQ ID NO 150 <400> SEQUENCE: 150 000 <210> SEQ ID NO 151 <400> SEQUENCE: 151 000 <210> SEQ ID NO 152 <211> LENGTH: 774 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CER97 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 152 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys 270 275 280 Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly 285 290 295 Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr 300 305 310 Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu 315 320 325 330 Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys 335 340 345 Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn 350 355 360 Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala 365 370 375 Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys 380 385 390 Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys 395 400 405 410 Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu 415 420 425 Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe 445 450 455 Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe 460 465 470 Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met 475 480 485 490 Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535

Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr 540 545 550 Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln 555 560 565 570 Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala 575 580 585 Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe 590 595 600 Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro 605 610 615 Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met Asp Glu Gly Gly 620 625 630 Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr 635 640 645 650 Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val 655 660 665 His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro 670 675 680 Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp 685 690 695 Gly Ala Tyr Phe Leu Gly Arg Leu Val Pro Arg Gly Arg Gly Ala Ala 700 705 710 Glu Ala Ala Thr Arg Lys Gln Arg Ile Thr Glu Thr Glu Ser Pro Tyr 715 720 725 730 Gln Glu Leu Gln Gly Gln Arg Ser Asp Val Tyr Ser Asp Leu Asn Thr 735 740 745 Gln Arg Pro Tyr Tyr Lys 750 <210> SEQ ID NO 153 <211> LENGTH: 767 <212> TYPE: PRT <213> ORGANISM: Artificial Sequence <220> FEATURE: <223> OTHER INFORMATION: CER98 chimeric engulfment receptor <220> FEATURE: <221> NAME/KEY: SIGNAL <222> LOCATION: (1)...(22) <400> SEQUENCE: 153 Met Ser Lys Gly Leu Leu Leu Leu Trp Leu Val Thr Glu Leu Trp Trp -20 -15 -10 Leu Tyr Leu Thr Pro Ala Ala Ser Glu Asp Thr Ile Ile Gly Phe Leu -5 1 5 10 Gly Gln Pro Val Thr Leu Pro Cys His Tyr Leu Ser Trp Ser Gln Ser 15 20 25 Arg Asn Ser Met Cys Trp Gly Lys Gly Ser Cys Pro Asn Ser Lys Cys 30 35 40 Asn Ala Glu Leu Leu Arg Thr Asp Gly Thr Arg Ile Ile Ser Arg Lys 45 50 55 Ser Thr Lys Tyr Thr Leu Leu Gly Lys Val Gln Phe Gly Glu Val Ser 60 65 70 Leu Thr Ile Ser Asn Thr Asn Arg Gly Asp Ser Gly Val Tyr Cys Cys 75 80 85 90 Arg Ile Glu Val Pro Gly Trp Phe Asn Asp Val Lys Lys Asn Val Arg 95 100 105 Leu Glu Leu Arg Arg Ala Thr Thr Thr Lys Lys Pro Thr Thr Thr Thr 110 115 120 Arg Pro Thr Thr Thr Pro Tyr Val Thr Thr Thr Thr Pro Glu Leu Leu 125 130 135 Pro Thr Thr Val Met Thr Thr Ser Val Leu Pro Thr Thr Thr Pro Pro 140 145 150 Gln Thr Leu Ala Thr Thr Ala Phe Ser Thr Ala Val Thr Thr Cys Pro 155 160 165 170 Ser Thr Thr Pro Gly Ser Phe Ser Gln Glu Thr Thr Lys Gly Ser Ala 175 180 185 Phe Thr Thr Glu Ser Glu Thr Leu Pro Ala Ser Asn His Ser Gln Arg 190 195 200 Ser Met Met Thr Ile Ser Thr Asp Ile Ala Val Leu Arg Pro Thr Gly 205 210 215 Ser Asn Pro Gly Ile Leu Pro Ser Thr Ser Gln Leu Thr Thr Gln Lys 220 225 230 Thr Thr Leu Thr Thr Ser Glu Ser Leu Gln Lys Thr Thr Lys Ser His 235 240 245 250 Gln Ile Asn Ser Arg Gln Thr Ile Leu Ile Ile Ala Cys Cys Val Gly 255 260 265 Phe Val Leu Met Val Leu Leu Phe Leu Ala Phe Leu His Arg Arg Lys 270 275 280 Lys Glu Thr Arg Tyr Gly Glu Val Phe Glu Pro Thr Val Glu Arg Gly 285 290 295 Glu Leu Val Val Arg Tyr Arg Val Arg Lys Ser Tyr Ser Arg Arg Thr 300 305 310 Thr Glu Ala Thr Leu Asn Ser Leu Gly Ile Ser Glu Glu Leu Lys Glu 315 320 325 330 Lys Leu Arg Asp Val Met Val Asp Arg His Lys Val Ala Leu Gly Lys 335 340 345 Thr Leu Gly Glu Gly Glu Phe Gly Ala Val Met Glu Gly Gln Leu Asn 350 355 360 Gln Asp Asp Ser Ile Leu Lys Val Ala Val Lys Thr Met Lys Ile Ala 365 370 375 Ile Cys Thr Arg Ser Glu Leu Glu Asp Phe Leu Ser Glu Ala Val Cys 380 385 390 Met Lys Glu Phe Asp His Pro Asn Val Met Arg Leu Ile Gly Val Cys 395 400 405 410 Phe Gln Gly Ser Glu Arg Glu Ser Phe Pro Ala Pro Val Val Ile Leu 415 420 425 Pro Phe Met Lys His Gly Asp Leu His Ser Phe Leu Leu Tyr Ser Arg 430 435 440 Leu Gly Asp Gln Pro Val Tyr Leu Pro Thr Gln Met Leu Val Lys Phe 445 450 455 Met Ala Asp Ile Ala Ser Gly Met Glu Tyr Leu Ser Thr Lys Arg Phe 460 465 470 Ile His Arg Asp Leu Ala Ala Arg Asn Cys Met Leu Asn Glu Asn Met 475 480 485 490 Ser Val Cys Val Ala Asp Phe Gly Leu Ser Lys Lys Ile Tyr Asn Gly 495 500 505 Asp Tyr Tyr Arg Gln Gly Arg Ile Ala Lys Met Pro Val Lys Trp Ile 510 515 520 Ala Ile Glu Ser Leu Ala Asp Arg Val Tyr Thr Ser Lys Ser Asp Val 525 530 535 Trp Ser Phe Gly Val Thr Met Trp Glu Ile Ala Thr Arg Gly Gln Thr 540 545 550 Pro Tyr Pro Gly Val Glu Asn Ser Glu Ile Tyr Asp Tyr Leu Arg Gln 555 560 565 570 Gly Asn Arg Leu Lys Gln Pro Ala Asp Cys Leu Asp Gly Leu Tyr Ala 575 580 585 Leu Met Ser Arg Cys Trp Glu Leu Asn Pro Gln Asp Arg Pro Ser Phe 590 595 600 Thr Glu Leu Arg Glu Asp Leu Glu Asn Thr Leu Lys Ala Leu Pro Pro 605 610 615 Ala Gln Glu Pro Asp Glu Ile Leu Tyr Val Asn Met Asp Glu Gly Gly 620 625 630 Gly Tyr Pro Glu Pro Pro Gly Ala Ala Gly Gly Ala Asp Pro Pro Thr 635 640 645 650 Gln Pro Asp Pro Lys Asp Ser Cys Ser Cys Leu Thr Ala Ala Glu Val 655 660 665 His Pro Ala Gly Arg Tyr Val Leu Cys Pro Ser Thr Thr Pro Ser Pro 670 675 680 Ala Gln Pro Ala Asp Arg Gly Ser Pro Ala Ala Pro Gly Gln Glu Asp 685 690 695 Gly Ala Asp Ser Lys Ala Gly Met Glu Glu Asp His Thr Tyr Glu Gly 700 705 710 Leu Asp Ile Asp Gln Thr Ala Thr Tyr Glu Asp Ile Val Thr Leu Arg 715 720 725 730 Thr Gly Glu Val Lys Trp Ser Val Gly Glu His Pro Gly Gln Glu 735 740 745

Claims

1. A chimeric engulfment receptor (CER) comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising a binding domain that binds to phosphatidylserine (PtdSer); an engulfment signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the engulfment signaling domain.

2. The CER of claim 1, wherein the binding domain comprises an scFv specific to PtdSer, or a PtdSer binding domain from Tim1, Tim4, Tim3, stabilin-2, receptor for advanced glycation endproducts (RAGE), brain-specific angiogenesis inhibitor 1 (BAI1), Milk Fat Globule-EGF Factor 8 Protein (MFG-E8), Growth Arrest Specific 6 (GAS6), protein S, protein C, Factor II, Factor VII, Factor IX, Factor X, Beta 2-glycoprotein I, .alpha.5.beta.3 integrin and other integrins, CR3 complement receptor, CR4 complement receptor, CD14, CD93, annexin V, phosphatidylserine receptor (PSr), prothrombin, or a scavenger receptor.

3. (canceled)

4. The CER of claim 1, wherein the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and transmembrane domain.

5. The CER of claim 4, wherein the extracellular spacer domain comprises an immunoglobulin hinge region, a hinge region of a type 1 membrane proteins, a stalk region of a type II C-lectin, an immunoglobulin constant domain, or a fragment thereof.

6.-7. (canceled)

8. The CER of claim 1, wherein the transmembrane domain comprises a Tim1, Tim4, Tim3, Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, CD8a, CD28, MERTK, Axl, Tyro3, BAI1, CD4, DAP12, or MRC1 transmembrane domain.

9.-11. (canceled)

12. The CER of claim 11, wherein the engulfment signaling domain is-comprises an ItgB5, MERTK, Tyro3, Axl, BAI1, ELMO, MRC1, PI3K Traf6, Syk, MyD88, Zap70 Fc.gamma.RI, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R, DAP12, NFAM1, or CD79b signaling domain.

13.-19. (canceled)

20. The CER of claim 1, wherein the engulfment signaling domain comprises a primary engulfment signaling domain and a secondary engulfment signaling domain.

21.-24. (canceled)

25. The CER of claim 20, wherein the primary engulfment signaling domain and secondary engulfment signaling domain are the same or different.

26. The CER of claim 20, wherein the primary engulfment signaling domain comprises an ItgB5, MERTK, Tyro3, Axl, BAI1, ELMO, MRC1, PI3K, Traf6, Syk, MyD88, Zap70, Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R, DAP12, NFAM1, or CD79b signaling domain.

27. (canceled)

28. The CER of claim 20, wherein the secondary engulfment signaling domain comprises an ItgB5, MERTK, Tyro3, Axl, BAI1, ELMO, MRC1, PI3K, Traf6, Syk, MyD88, Zap70, Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R, DAP12, NFAM1, or CD79b signaling domain.

29.-43. (canceled)

44. A chimeric engulfment receptor (CER) comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising a binding domain that binds to a pro-engulfment marker or target antigen; an engulfment signaling domain comprising a PI3K, Traf6, Syk, MyD88, Zap70, Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R DAP12, NFAM1, or CD79b signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the Engulfment signaling domain.

45. The CER of claim 44, wherein: (i) the binding domain binds to a pro-engulfment marker selected from phosphatidylserine (PtdSer), ICAM-3, oxidized low density lipoprotein, calreticulin, annexin I, complement C1q, and thrombospondin; (ii) the binding domain comprises a scFv specific for a tumor antigen; or (iii) the binding domain comprises a scFv specific for an antigen of a microbe that is capable of establishing a persistent infection in a host.

46. The CER of claim 45, wherein: (i) the binding domain binds to PtdSer and comprises an scFv specific to PtdSer, or comprises a PtdSer binding domain from Tim1, Tim4, Tim3, stabilin-2, receptor for advanced glycation endproducts (RAGE), brain-specific angiogenesis inhibitor 1 (BAI1), Milk Fat Globule-EGF Factor 8 Protein (MFG-E8), Growth Arrest Specific 6 (GAS6), protein S, protein C, Factor II, Factor VII, Factor IX, Factor X, Beta 2-glycoprotein I, .alpha.5.beta.3 integrin and other integrins, CR3 complement receptor, CR4 complement receptor, CD14, CD93, annexin V, phosphatidylserine receptor (PSr), prothrombin, or a scavenger receptor; or (ii) the binding domain comprises a scFv specific for a tumor antigen selected from CD138, CD38, CD33, CD123, CD72, CD79a, CD79b, mesothelin, PSMA, BCMA, ROR1, MUC-16, L1CAM, CD22, CD19, CD20, CD23, CD24, CD37, CD30, CA125, CD56, c-Met, EGFR GD-3, HPV E6, HPV E7, MUC-1, HER2, folate receptor .alpha. CD97, CD171, CD179a, CD44v6, WT1, VEGF-.alpha., VEGFR1, IL-13R1, IL-13R.alpha.2, IL-11R.alpha., PSA, FcRH5, NKG2D ligand, NY-ESO-1, TAG-72, CEA, ephrin A2, ephrin B2, Lewis A antigen, Lewis Y antigen, MAGE, MAGE-A1, RAGE-1, folate receptor B, EGFRviii, VEGFR-2, LGR5, SSX2, AKAP-4, FLT3, fucosyl GM1, GM3, o-acetyl-GD2, and GD2.

47.-49. (canceled)

50. The CER of claim 44, wherein the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and transmembrane domain.

51. The CER of claim 50, wherein the extracellular spacer domain comprises an immunoglobulin hinge region, an extracellular region of a type 1 membrane proteins, a stalk region of a type II C-lectin, an immunoglobulin constant domain, or a fragment thereof.

52.-53. (canceled)

54. The CER of claim 44, wherein the transmembrane domain comprises a Tim1, Tim4, Tim3, FcR, CD8a, CD28, MERTK, Axl, Tyro3, BAI1, CD4, MRC1, or DAP12 transmembrane domain.

55.-60. (canceled)

61. A chimeric engulfment receptor (CER) comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising a binding domain that binds to a pro-engulfment marker or target antigen; an engulfment signaling domain comprising a primary engulfment signaling domain and a secondary engulfment signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the primary engulfment signaling domain.

62. The CER of claim 61, wherein: (i) the binding domain binds to a pro-engulfment marker selected from phosphatidylserine (PtdSer), ICAM-3, oxidized low density lipoprotein, calreticulin, annexin I, complement C1q, and thrombospondin; (ii) the binding domain comprises a scFv specific for a tumor antigen; or (iii) the binding domain comprises a scFv specific for a microbial antigen.

63. The CER of claim 62, wherein: (i) the binding domain that binds to PtdSer and comprises a scFv specific to PtdSer, or comprises a PtdSer binding domain from Tim1, Tim4, Tim3, stabilin-2, receptor for advanced glycation endproducts (RAGE), brain-specific angiogenesis inhibitor 1 (BAI1), Milk Fat Globule-EGF Factor 8 Protein (MFG-E8), Growth Arrest Specific 6 (GAS6), protein S, protein C, Factor II, Factor VII, Factor IX, Factor X, Beta 2-glycoprotein I, .alpha.5.beta.3 integrin and other integrins, CR3 complement receptor, CR4 complement receptor, CD14, CD93, annexin V, phosphatidylserine receptor (PSr), prothrombin, or a scavenger receptor; or (ii) the binding domain comprises a scFv specific for a tumor antigen selected from CD138, CD38, CD33, CD123, CD72, Cd79a, CD79b, mesothelin, PSMA, BCMA, ROR1, MUC-16, L1CAM, CD22, CD19, CD20, CD23, CD24, CD37, CD30, CA125, CD56, c-Met, EGFR, GD-3, HPV E6, HPV E7, MUC-1, HER2, folate receptor .alpha., CD97, CD171, CD179a, CD44v6, WT1, VEGF-.alpha., VEGFR1, IL-13R.alpha.2, IL-13R.alpha.1, IL-11R.alpha., PSA, FcRH5, NKG2D ligand, NY-ESO-1, TAG-72, CEA, ephrin A2, ephrin B2, Lewis A antigen, Lewis Y antigen, MAGE, MAGE-A1, RAGE-1, folate receptor .beta., EGFRviii, VEGFR-2, LGR5, SSX2, AKAP-4, FLT3, fucosyl GM1, GM3, o-acetyl-GD2, and GD2.

64.-66. (canceled)

67. The CER of claim 61, wherein the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and transmembrane domain.

68. The CER of claim 67, wherein the extracellular spacer domain comprises an immunoglobulin hinge region, an extracellular region of a type 1 membrane proteins, a stalk region of a type II C-lectin, an immunoglobulin constant domain, or a fragment thereof.

69.-70. (canceled)

71. The CER of claim 61, wherein the transmembrane domain comprises a Tim1, Tim4, Tim3, FcR, CD8a, CD28, MERTK, Axl, Tyro3, BAI1, CD4, MRC1, or DAP12 transmembrane domain.

72.-77. (canceled)

78. The CER of claim 61, wherein the primary engulfment signaling domain and secondary engulfment signaling domain are the same or different.

79. The CER of claim 61, wherein the primary engulfment signaling domain comprises an ItgB5, MERTK, Tyro3, Axl, BAI1, ELMO, MRC1, PI3K, Traf6, Syk, MyD88, Zap70, Fc.alpha.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R DAP12, NFAM1, or CD79b signaling domain.

80. (canceled)

81. The CER of any one of claim 61, wherein the secondary engulfment signaling domain comprises an ItgB5, MERTK, Tyro3, Axl, BAI1, ELMO, MRC1, PI3K, Traf6, Syk, MyD88, Zap70, Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A, Fc.epsilon.R1, Fc.alpha.R1, BAFF-R, DAP12, NFAM1, or CD79b signaling domain.

82. (canceled)

83. A chimeric engulfment receptor (CER) comprising a single chain chimeric protein, the single chain chimeric protein comprising: an extracellular domain comprising a scFv that binds to a pro-engulfment marker or target antigen; an engulfment signaling domain; and a transmembrane domain positioned between and connecting the extracellular domain and the engulfment signaling domain, wherein the transmembrane domain and engulfment signaling domain are each derived from a different molecule.

84. The CER of claim 83, wherein: (i) the scFv binds to a pro-engulfment marker selected from phosphatidylserine (PtdSer), ICAM-3, oxidized low density lipoprotein, calreticulin, annexin I, complement C1q, and thrombospondin, (ii) the scFv binds to a tumor antigen selected from CD138, CD38, CD33, CD123, CD72, CD79a, CD79b, mesothelin, PSMA, BCMA, ROR1, MUC-16, L1CAM, CD22, CD19, CD20, CD23, CD24, CD37, CD30, CA125, CD56, c-Met, EGFR GD-3, HPV E6, HPV E7, MUC-1, HER2, folate receptor .alpha., CD97, CD171, CD179a, CD44v6, WT1, VEGF-.alpha., VEGFR1, IL-13R.alpha.2, IL-11R.alpha., PSA, FcRH5, NKG2D ligand, NY-ESO-1, TAG-72, CEA, ephrin A2, ephrin B2, Lewis A antigen, Lewis Y antigen, MAGE, MAGE-A1, RAGE-1, folate receptor .beta., EGFRviii, VEGFR-2, LGR5, SSX2, AKAP-4, FLT3, fucosyl GM1, o-acetyl GD2, and GD2; or (iii) the scFv binds to a microbial antigen.

85.-87. (canceled)

88. The CER of claim 83, wherein the extracellular domain further comprises an extracellular spacer domain positioned between the binding domain and transmembrane domain.

89. The CER of claim 88, wherein the extracellular spacer domain comprises an immunoglobulin hinge region, an extracellular region of a type 1 membrane protein, a stalk region of a type II C-lectin, an immunoglobulin constant domain, or a fragment thereof.

90.-91. (canceled)

92. The CER of claim 83, wherein the transmembrane domain comprises a Tim1, Tim4, Tim3, FcR, CD8a, CD28, MERTK, Axl, Tyro3, BAI1, CD4, MRC1, or DAP12 transmembrane domain.

93.-95. (canceled)

96. The CER of claim 83, wherein the engulfment signaling domain is-comprises an ItgB5, MERTK, Tyro3, Axl, BAI1, ELMO, MRC1, PI3K, Traf6, Syk, MyD88, Zap70 Fc.gamma.R1, Fc.gamma.R2A, Fc.gamma.R2B2, Fc.gamma.R2C, Fc.gamma.R3A Fc.epsilon.R1, Fc.alpha.R1, BAFF-R, DAP12, NFAM1, or CD79b signaling domain.

97.-105. (canceled)

106. A nucleic acid molecule encoding a CER according to claim 1.

107.-112. (canceled)

113. A vector comprising a nucleic acid molecule according to claim 106.

114.-116. (canceled)

117. A genetically modified cell comprising a CER according to claim 1.

118.-123. (canceled)

124. The genetically modified cell according to claim 117, wherein the genetically modified cell is a T cell, including CD4.sup.+, CD8.sup.+, naive (CD45 RA+, CCR7+, CD62L+, CD27+, CD45RO-), central memory (CD45RO.sup.+, CD62L.sup.+, CD8.sup.+), effector memory (CD45RA+, CD45RO-, CCR7-, CD62L-, CD27-), virus-specific, mucosal-associated invariant, .gamma..delta. (gd), natural killer, and tissue resident T cells, a natural killer cell, a B cell, or a lymphoid precursor cell, including common lymphocyte precursor cells, an antigen presenting cell, including dendritic cells, a Langerhans cell, a myeloid precursor cell, or a mature myeloid cell.

125.-126. (canceled)

127. The modified host cell of claim 117, wherein the modified host cell exhibits: (i) engulfment activity when the extracellular domain of the CER binds to PtdSer; (ii) phagocytic activity when the extracellular domain of the CER binds to PtdSer; or (iii) a phagocytic index of at least 20 towards a target cell.

128.-132. (canceled)

133. A composition comprising a plurality of genetically modified cells according to claim 117, and a pharmaceutically acceptable excipient.

134. A method of treating a subject with cancer or treating a subject having a disease, disorder, or undesired condition associated with an overexpression of a tumor antigen, the method comprising administering to the subject an effective amount of composition of claim 133.

135.-151. (canceled)

152. A nucleic acid molecule encoding a CER according to claim 44.

153. A vector comprising a nucleic acid molecule according to claim 152.

154. A genetically modified cell comprising a CER according to claim 44

155. A composition comprising a plurality of genetically modified cells according to claim 154 and a pharmaceutically acceptable excipient.

156. A method of treating a subject with cancer or treating a subject having a disease, disorder, or undesired condition associated with an overexpression of a tumor antigen, the method comprising administering to the subject an effective amount of a composition of claim 155.

157. A method of treating a subject having an autoimmune disease, disorder, or undesired condition, the method comprising administering to the subject an effective amount of a composition of claim 155.

158. A method of treating or preventing an infectious disease in a subject, the method comprising administering to the subject an effective amount of a composition of claim 155.

159. A nucleic acid molecule encoding a CER according to claim 61.

160. A vector comprising a nucleic acid molecule according to claim 159.

161. A genetically modified cell comprising a CER according to claim 61.

162. A composition comprising a plurality of genetically modified cells according to claim 161 and a pharmaceutically acceptable excipient.

163. A method of treating a subject with cancer or treating a subject having a disease, disorder, or undesired condition associated with an overexpression of a tumor antigen, the method comprising administering to the subject an effective amount of a composition of claim 162.

164. A method of treating a subject having an autoimmune disease, disorder, or undesired condition, the method comprising administering to the subject an effective amount of a composition of claim 162.

165. A method of treating or preventing an infectious disease in a subject, the method comprising administering to the subject an effective amount of a composition of claim 162.

166. A nucleic acid molecule encoding a CER according to claim 83.

167. A vector comprising a nucleic acid molecule according to claim 166.

168. A genetically modified cell comprising a CER according to claim 83.

169. A composition comprising a plurality of genetically modified cells according to claim 168 and a pharmaceutically acceptable excipient.

170. A method of treating a subject with cancer or treating a subject having a disease, disorder, or undesired condition associated with an overexpression of a tumor antigen, the method comprising administering to the subject an effective amount of a composition of claim 169.

171. A method of treating a subject having an autoimmune disease, disorder, or undesired condition, the method comprising administering to the subject an effective amount of a composition of claim 169.

172. A method of treating or preventing an infectious disease in a subject, the method comprising administering to the subject an effective amount of a composition of claim 169.