Cells and compositions for b cell depletion

Abstract

The presently disclosed subject matter provides cells, compositions, and methods for inducing B cell depletion. It relates to cells comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) targeting a B cell antigen (e.g., CD19, FcRLS, etc.).

Description

[0001]072734.1806 PATENT CELLS AND COMPOSITIONS FOR B CELL DEPLETION CROSS-REFERENCE TO RELATED APPLICATION This application claims priority to U.S. Provisional Application No.63 / 679,532, filed August 5, 2024, the content of which is hereby incorporated by reference in its entirety, and to which priority is claimed. SEQUENCE LISTING A Sequence Listing conforming to the rules of WIPO Standard ST.26 is hereby incorporated by reference. Said Sequence Listing has been filed as an electronic document via Patent Center encoded as XML in UTF-8 text. The electronic document, created on July 24, 2025, is entitled “072734.1806_ST26.xml”, and is 145,236 bytes in size. INTRODUCTION The presently disclosed subject matter provides compositions and methods for inducing B cell depletion. It relates to compositions, e.g., modified immunoresponsive cells, comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) targeting a B cell antigen (e.g., CD19, FcRL5, etc.), where the compositions mediate a modulation of immune response. BACKGROUND OF THE INVENTION Suppressing alloimmune responses is one of the main challenges in transplantation and transfusion clinical practice. Prevention of rejection has relied so far on immunosuppressive drugs, but despite major advances, modern immunosuppressive regimens remain responsible for high morbidity and mortality. In addition, current regimens only partially block the alloimmune response and often fail to prevent the development of chronic rejections, which remains the primary cause of allograft loss. Thus, unmet need remains for new therapies that can exclusively target anti-donor immune responses while preserving other aspects of normal immunity. SUMMARY OF THE INVENTION The presently disclosed subject matter relates to a method of treating an allo-immunized subject. Additionally or alternatively, the presently disclosed subject matter relates to a method of inducing B cell depletion in an allo-immunized subject. In certain embodiments, the method includes administering to the subject an effective amount of a cell including an antigen- ACTIVE 511192992.1 1 072734.1806 PATENT recognizing receptor that targets a B cell antigen. In certain embodiments, the method includes administering to the subject an effective amount of a cell including an antigen-recognizing receptor that targets CD19 or FcRL5. In certain embodiments, the antigen-recognizing receptor is a chimeric antigen receptor (CAR) or a TCR-like fusion molecule. In certain embodiments, the antigen-recognizing receptor is a chimeric antigen receptor (CAR). In certain embodiments, the CAR includes an extracellular antigen-binding domain that binds to the first antigen, and an intracellular signaling domain that is capable of delivering an activation signal to the cell. In certain embodiments, the intracellular signaling domain of the CAR includes a CD3ζ polypeptide. In certain embodiments, the CD3ζ polypeptide is a native CD3ζ polypeptide or a modified CD3ζ polypeptide. In certain embodiments, the modified CD3ζ polypeptide includes a native ITAM1, an ITAM2 variant consisting of two loss-of-function mutations, and an ITAM3 variant consisting of two loss-of-function mutations. In certain embodiments, the native ITAM1 consists of the amino acid sequence In certain embodiments, the modified CD3ζ polypeptide includes the amino acid sequence set forth in SEQ ID NO: 30. In certain embodiments, the intracellular signaling domain of the CAR further includes at least one costimulatory signaling region. In certain embodiments, the at least one costimulatory signaling region includes at least an intracellular domain of a costimulatory molecule or a portion thereof. In certain embodiments, the costimulatory molecule is selected from the group consisting of CD28, 4-1BB, OX40, CD27, CD40, CD154, CD97, CD11a / CD18, ICOS, DAP-10, CD2, CD150, CD226, and NKG2D. In certain embodiments, the at least one costimulatory signaling region includes a CD28 polypeptide. In certain embodiments, the costimulatory molecule includes amino acids 180 to 220 of SEQ ID NO: 15. In certain embodiments, the CAR includes a transmembrane domain. In certain embodiments, the transmembrane domain includes a CD8 polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD4 polypeptide, a 4-1BB polypeptide, a OX40 polypeptide, an ICOS polypeptide, a CTLA-4 polypeptide, a PD-1 polypeptide, a LAG-3 polypeptide, a 2B4 polypeptide, or a BTLA polypeptide. In certain embodiments, the transmembrane domain includes a CD28 polypeptide. In certain embodiments, the antigen-recognizing receptor is a TCR-like fusion molecule. In certain embodiments, the TCR-like fusion molecule includes (a) a first antigen- binding chain including an antigen-binding fragment of a heavy chain variable region (VH) of an antibody; and (b) a second antigen-binding chain including an antigen-binding fragment of a light chain variable region (VL) of the antibody; wherein the first and second antigen-binding ACTIVE 511192992.1 2 072734.1806 PATENT chains (i) each include the TRAC polypeptide or the TRBC polypeptide, and (ii) bind to the second antigen, wherein the TCR-like fusion molecule binds to the second antigen in an HLA- independent manner. In certain embodiments, at least one of the TRAC polypeptide and the TRBC polypeptide is endogenous. In certain embodiments, (a) the first antigen-binding chain includes an antigen-binding fragment of a VH of an antibody and a TRBC polypeptide, and the second antigen-binding chain includes an antigen-binding fragment of a VL of the antibody and a TRAC polypeptide; or (b) the first antigen-binding chain includes an antigen-binding fragment of a VH of an antibody and a TRAC polypeptide, and the second antigen-binding chain includes an antigen-binding fragment of a VL of the antibody and a TRBC polypeptide. In certain embodiments, the antigen-recognizing receptor is encoded by a polynucleotide integrated at a locus within the genome of the cell. In certain embodiments, the locus is selected from the group consisting of a TRAC locus, a TRBC locus, a TRDC locus, and a TRGC locus. In certain embodiments, the locus is a TRAC locus or a TRBC locus. In certain embodiments, the locus is a TRAC locus. In certain embodiments, the cell further includes a gene disruption of a TRAC locus or a TRBC locus. In certain embodiments, the cell further includes a gene modification of a TRAC locus and a TRBC locus. In certain embodiments, the cell is a cell of the lymphoid lineage or a cell of the myeloid lineage. In certain embodiments, the cell of the lymphoid lineage is selected from the group consisting of a T cell or a Natural Killer (NK) cell. In certain embodiments, the cell is a T cell. In certain embodiments, the T cell is derived from an induced pluripotent stem cell. In certain embodiments, the T cell is a CD8+ T cell. In certain embodiments, the CD8+ T cell is CD4 independent. In certain embodiments, the T cell is selected from the group consisting of a cytotoxic T lymphocyte (CTL), a γδ T cell, a tumor-infiltrating lymphocyte (TIL), a regulatory T cell, and a Natural Killer T (NKT) cell. In certain embodiments, the T cell is CD62L+. In certain embodiments, the T cell is CD45RA+. In certain embodiments, the T cell is CD45RA+ and CD62L+. In certain embodiments, the cell further includes at least one exogenous costimulatory ligand. In certain embodiments, the at least one exogenous costimulatory ligand includes CD80. In certain embodiments, the at least one exogenous a costimulatory ligand includes 4- 1BBL. In certain embodiments, the cell includes two exogenous costimulatory ligands. In certain embodiments, the at least two exogenous costimulatory ligands include CD80 and 4- 1BBL. ACTIVE 511192992.1 3 072734.1806 PATENT In certain embodiments, the cell further includes a fusion polypeptide including: a) an extracellular domain and a transmembrane domain of a co-stimulatory ligand, and b) an intracellular domain of a first co-stimulatory molecule. In certain embodiments, the co- stimulatory ligand is CD80. In certain embodiments, the first co-stimulatory molecule is 4- 1BB. In certain embodiments, the co-stimulatory ligand is CD80 and the first co-stimulatory molecule is 4-1BB. In certain embodiments, the fusion polypeptide includes the amino acid sequence set forth in SEQ ID NO: 68. In certain embodiments, the fusion polypeptide further includes an intracellular domain of a second co-stimulatory molecule. In certain embodiments, the second co-stimulatory molecule is CD28. In certain embodiments, the co-stimulatory ligand is CD80, the first co-stimulatory molecule is 4-1BB, and the second co-stimulatory molecule is CD28. In certain embodiments, the fusion polypeptide includes the amino acid sequence set forth in SEQ ID NO: 69. In certain embodiments, the cell is autologous. In certain embodiments, the cell is allogeneic. In certain embodiments, the allogeneic cell is HLA-negative or HLA-class I negative. In certain embodiments, the subject has a hemoglobinopathy or a thalassemia. In certain embodiments, the hemoglobinopathy is selected from hemoglobin C disease, hemoglobin sickle cell disease (SCD), sickle cell anemia, or hereditary anemia. In certain embodiments, the hemoglobinopathy is sickle cell disease. In certain embodiments, the hemoglobinopathy is sickle cell anemia. In certain embodiments, the thalassemia is selected from thalassemia, β-thalassemia, thalassemia major, thalassemia intermedia, α-thalassemia, or hemoglobin H disease. In certain embodiments, the thalassemia is β-thalassemia. In certain embodiments, the method further comprises administering an effective amount of a second therapeutic agent. In certain embodiments, the second therapeutic agent is selected from blood transfusions, iron chelation agents, hydroxyurea, crizanlizumab, L- glutamine, hematopoietic stem cell transplantation, sirolimus, thalidomide, luspatercept, or a combination thereof. In certain embodiments, the second therapeutic agent is exagamglogene autotemcel or lovotibeglogene autotemcel. In certain embodiments, the subject is a recipient or a prospective recipient of a transplant. In certain embodiments, the transplant is selected from heart transplant, lung transplant, kidney transplant, liver transplant, islets transplant, pancreas transplant, or skin transplant. In certain embodiments, the transplant is a kidney transplant. In certain embodiments, the transplant is an HLA-mismatched transplant. ACTIVE 511192992.1 4 072734.1806 PATENT In certain embodiments, the transplant is a stem cell transplantation. In certain embodiments, the stem cell transplantation is a hematopoietic stem cell transplantation, an allogenic stem cell transplantation, or an allogenic hematopoietic stem cell transplantation. In certain embodiments, the transplantation is an HLA-mismatched transplantation. DETAILED DESCRIPTION OF THE INVENTION The presently disclosed subject matter provides compositions, e.g., modified immune cells, useful for B cell depletion. The presently disclosed compositions, modified immunoresponsive cells comprising an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) targeting a B cell antigen (e.g., CD19, FcRL5, etc.), where the compositions mediate a modulation of immune response. The presently disclosed subject matter also provides methods for producing such compositions, and methods of using such compositions for inducing B cell depletion, treating and / or preventing diseases (e.g., autoimmune diseases) in allo-immunized subject. The presently disclosed subject matter is based, at least in part, on the discovery that a CAR T cells targeting a B cell antigen (e.g., CD19, FcRL5, etc.) and including a 1XX intracellular domain can be used in allo-immunized subjects in whom transplants or gene therapies cannot be performed because of life-threatening allo-antibodies (e.g., anti-HLA, anti-blood group, and other antibodies). Non-limiting embodiments of the presently disclosed subject matter are described by the present specification and Examples. For purposes of clarity of disclosure and not by way of limitation, the detailed description is divided into the following subsections: 1. Definitions; 2. Cells; 3. Nucleic Acids and Vectors; 4. Formulations and Administration; 5. Methods of Treatment; and 6. Kits. 1. Definitions Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art. The following references provide one of skill with a general definition of many of the terms used in the presently disclosed subject matter: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The ACTIVE 511192992.1 5 072734.1806 PATENT Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the term “about” or “approximately” means within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, “about” can mean within 3 or more than 3 standard deviations, per the practice in the art. Alternatively, “about” can mean a range of up to 20%, e.g., up to 10%, up to 5%, or up to 1% of a given value. Alternatively, particularly with respect to biological systems or processes, the term can mean within an order of magnitude, e.g., within 5-fold or within 2-fold, of a value. As used herein, a “co-stimulatory molecule” refers to a cell surface molecule other than an antigen receptor or its ligand that can provide an efficient response of lymphocytes to an antigen. In certain embodiments, a co-stimulatory molecule can provide optimal lymphocyte activation. As used herein, a “co-stimulatory ligand” refers to a molecule that upon binding to its receptor (e.g., a co-stimulatory molecule) produces a co-stimulatory response, e.g., an intracellular response that effects the stimulation provided when an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR)) binds to its target antigen. By “immunoresponsive cell” is meant a cell that functions in an immune response or a progenitor, or progeny thereof. In certain embodiments, the immunoresponsive cell is a cell of lymphoid lineage. Non-limiting examples of cells of lymphoid lineage include T cells, Natural Killer (NK) cells, B cells, and stem cells from which lymphoid cells may be differentiated. In certain embodiments, the immunoresponsive cell is a cell of myeloid lineage. By “activates an immunoresponsive cell” is meant induction of signal transduction or changes in protein expression in the cell resulting in initiation of an immune response. For example, when CD3 Chains cluster in response to ligand binding and immunoreceptor tyrosine- based inhibition motifs (ITAMs) a signal transduction cascade is produced. In certain embodiments, when an endogenous TCR or an exogenous CAR binds to an antigen, a formation of an immunological synapse occurs that includes clustering of many molecules near the bound receptor (e.g. CD4 or CD8, CD3^ / ^ / ^ / ^, etc.). This clustering of membrane bound signaling molecules allows for ITAM motifs contained within the CD3 chains to become phosphorylated. This phosphorylation in turn initiates a T cell activation pathway ultimately activating transcription factors, such as NF-^B and AP-1. These transcription factors induce ACTIVE 511192992.1 6 072734.1806 PATENT global gene expression of the T cell to increase IL-2 production for proliferation and expression of master regulator T cell proteins in order to initiate a T cell mediated immune response. By “stimulates an immunoresponsive cell” is meant a signal that results in a robust and sustained immune response. In various embodiments, this occurs after immune cell (e.g., T- cell) activation or concomitantly mediated through receptors including, but not limited to, CD28, CD137 (4-1BB), OX40, CD40, ICOS, DAP-10, CD27, NKG2D, CD2, CD150, CD226. Receiving multiple stimulatory signals can be important to mount a robust and long-term T cell mediated immune response. T cells can quickly become inhibited and unresponsive to antigen. While the effects of these co-stimulatory signals may vary, they generally result in increased gene expression in order to generate long lived, proliferative, and anti-apoptotic T cells that robustly respond to antigen for complete and sustained eradication. As used herein, the term “antigen heterogeneity” refers to the differential expression of a number of antigens (e.g., tumor antigens, e.g., CD70, CD312) which results in variation in the tumor cell phenotype and distribution of tumor antigen-positive cells. As used herein, the term “low antigen density” refers to a target molecule (e.g., an antigen) having a cell surface density of less than about 5,000 molecules per cell. In certain embodiments, the low antigen density is a cell surface density is less than about 4,000 molecules per cell, less than about 3,000 molecules per cell, less than about 2,000 molecules per cell, less than about 1,500 molecules per cell, less than about 1,000 molecules per cell, less than about 500 molecules per cell, less than about 200 molecules per cell, or less than about 100 molecules per cell. In certain embodiments, the low antigen density is a cell surface density is less than about 2,000 molecules per cell. In certain embodiments, the low antigen density is a cell surface density is less than about 1,500 molecules per cell. In certain embodiments, the low antigen density is a cell surface density is less than about 1,000 molecules per cell. In certain embodiments, the low antigen density is a cell surface density is between about 4,000 molecules per cell and about 2,000 molecules per cell, between about 2,000 molecules per cell and about 1,000 molecules per cell, between about 1,500 molecules per cell and about 1,000 molecules per cell, between about 2,000 molecules per cell and about 500 molecules per cell, between about 1,000 molecules per cell and about 200 molecules per cell, or between about 1,000 molecules per cell and about 100 molecules per cell. As used herein, the term “low tumor cell frequency” refers to a target cell having a target cell frequency of less than about 50% per tumor. In certain embodiments, the low tumor cell frequency is less than about 40% per tumor, less than about 30% per tumor, less than about 20% per tumor, less than about 15% per tumor, less than about 10% per tumor, less than about ACTIVE 511192992.1 7 072734.1806 PATENT 5% per tumor, less than about 2% per tumor, or less than about 1% per tumor. In certain embodiments, the low tumor cell frequency is less than about 2% per tumor. In certain embodiments, the low tumor cell frequency is less than about 1.5% per tumor. In certain embodiments, the low tumor cell frequency is less than about 1% per tumor. In certain embodiments, the low tumor cell frequency is between about 40% per tumor and about 20% per tumor, between about 20% per tumor and about 10% per tumor, between about 15% per tumor and about 10% per tumor, between about 20% per tumor and about 5% per tumor, between about 10% per tumor and about 2% per tumor, or between about 10% per tumor and about 1% per tumor. The term “antigen-recognizing receptor” as used herein refers to a receptor that is capable of activating an immune or immunoresponsive cell (e.g., a T-cell) in response to its binding to an antigen. As used herein, the term “antibody” means not only intact antibody molecules, but also fragments of antibody molecules that retain immunogen-binding ability. Such fragments are also well known in the art and are regularly employed both in vitro and in vivo. Accordingly, as used herein, the term “antibody” means not only intact immunoglobulin molecules but also the well-known active fragments F(ab')2, and Fab. F(ab')2, and Fab fragments that lack the Fe fragment of intact antibody, clear more rapidly from the circulation, and may have less non- specific tissue binding of an intact antibody (Wahl et al., J. Nucl. Med.24:316-325 (1983). As used herein, antibodies include whole native antibodies, bispecific antibodies; chimeric antibodies; Fab, Fab’, single chain variable fragment (scFv), fusion polypeptides, and unconventional antibodies. In certain embodiments, an antibody is a glycoprotein comprising at least two heavy (H) chains and two light (L) chains inter-connected by disulfide bonds. Each heavy chain is comprised of a heavy chain variable region (abbreviated herein as VH) and a heavy chain constant (CH) region. The heavy chain constant region is comprised of three domains, CH1, CH2 and CH3. Each light chain is comprised of a light chain variable region (abbreviated herein as VL) and a light chain constant CLregion. The light chain constant region is comprised of one domain, CL. The VH and VL regions can be further sub-divided into regions of hypervariability, termed complementarity determining regions (CDR), interspersed with regions that are more conserved, termed framework regions (FR). Each VHand VLis composed of three CDRs and four FRs arranged from amino-terminus to carboxy-terminus in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The variable regions of the heavy and light chains contain a binding domain that interacts with an antigen. The constant regions of the antibodies may mediate the binding of the immunoglobulin to host tissues or factors, ACTIVE 511192992.1 8 072734.1806 PATENT including various cells of the immune system (e.g., effector cells) and the first component (C1 q) of the classical complement system. As used herein, “CDRs” are defined as the complementarity determining region amino acid sequences of an antibody which are the hypervariable regions of immunoglobulin heavy and light chains. See, e.g., Kabat et al., Sequences of Proteins of Immunological Interest, 4th U. S. Department of Health and Human Services, National Institutes of Health (1987). Generally, antibodies comprise three heavy chain and three light chain CDRs or CDR regions in the variable region. CDRs provide the majority of contact residues for the binding of the antibody to the antigen or epitope. In certain embodiments, the CDRs regions are delineated using the Kabat system (Kabat, E. A., et al. (1991) Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242). In certain embodiments, the CDRs regions are delineated using the PyIgClassify system (Adolf-Bryfogle et al., Nucleic acids research 43.D1 (2015): D432-D438). As used herein, the term “Linker” shall mean a functional group (e.g., chemical or polypeptide) that covalently attaches two or more polypeptides or nucleic acids so that they are connected to one another. As used herein, a “peptide linker” refers to one or more amino acids used to couple two proteins together (e.g., to couple VHand VLdomains). In certain embodiments, the linker is a G4S linker. In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 1, which is provided below: GGGGSGGGGSGGGGS [SEQ ID NO: 1] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 2, which is provided below: GGGGSGGGGSGGGSGGGGS [SEQ ID NO: 2] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 3, which is provided below: GGGGSGGGGSGGGGSGGGSGGGGS [SEQ ID NO: 3] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 4, which is provided below: GGGGSGGGGSGGGGSGGGGSGGGSGGGGS [SEQ ID NO: 4] In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 5, which is provided below: GGGGS [SEQ ID NO: 5] ACTIVE 511192992.1 9 072734.1806 PATENT In certain embodiments, the linker comprises or consists of the amino acid sequence set forth in SEQ ID NO: 6, which is provided below: GGGGSGGGGS [SEQ ID NO: 6] As used herein, the term “single-chain variable fragment” or “scFv” is a fusion protein of the variable regions of the heavy (VH) and light chains (VL) of an immunoglobulin covalently linked to form a VH::VL heterodimer. The VH and VL are either joined directly or joined by a peptide-encoding linker (e.g., 10, 15, 20, 25 amino acids), which connects the N-terminus of the VHwith the C­terminus of the VL, or the C-terminus of the VHwith the N-terminus of the VL. The linker is usually rich in glycine for flexibility, as well as serine or threonine for solubility. Despite removal of the constant regions and the introduction of a linker, scFv proteins retain the specificity of the original immunoglobulin. Single chain Fv polypeptide antibodies can be expressed from a nucleic acid including VH - and VL ­encoding sequences as described by Huston, et al. (Proc. Nat. Acad. Sci. USA, 85:5879-5883, 1988). See, also, U.S. Patent Nos. 5,091,513, 5,132,405 and 4,956,778; and U.S. Patent Publication Nos. 20050196754 and 20050196754. Antagonistic scFvs having inhibitory activity have been described (see, e.g., Zhao et al., Hyrbidoma (Larchmt) 2008 27(6):455-51; Peter et al., J Cachexia Sarcopenia Muscle 2012 August 12; Shieh et al., J Imunol2009 183(4):2277-85; Giomarelli et al., Thromb Haemost 2007 97(6):955-63; Fife eta., J Clin Invst 2006 116(8):2252-61; Brocks et al., Immunotechnology 19973(3):173-84; Moosmayer et al., Ther Immunol 19952(10:31-40). Agonistic scFvs having stimulatory activity have been described (see, e.g., Peter et al., J Bioi Chern 2003 25278(38):36740-7; Xie et al., Nat Biotech 1997 15(8):768-71; Ledbetter et al., Crit Rev Immunol1997 17(5-6):427-55; Ho et al., BioChim Biophys Acta 20031638(3):257-66). As used herein, the term “affinity” is meant a measure of binding strength. Affinity can depend on the closeness of stereochemical fit between antibody combining sites and antigen determinants, on the size of the area of contact between them, and / or on the distribution of charged and hydrophobic groups. As used herein, the term “affinity” also includes “avidity”, which refers to the strength of the antigen-antibody bond after formation of reversible complexes. Methods for calculating the affinity of an antibody for an antigen are known in the art, including, but not limited to, various antigen-binding experiments, e.g., functional assays (e.g., flow cytometry assay). The term “chimeric antigen receptor” or “CAR” as used herein refers to a molecule comprising an extracellular antigen-binding domain that is fused to an intracellular signaling ACTIVE 511192992.1 10 072734.1806 PATENT domain that is capable of activating or stimulating an immune or immunoresponsive cell, and a transmembrane domain. In certain embodiments, the extracellular antigen-binding domain of a CAR comprises an scFv. The scFv can be derived from fusing the variable heavy and light regions of an antibody. Alternatively or additionally, the scFv may be derived from Fab’s (instead of from an antibody, e.g., obtained from Fab libraries). In certain embodiments, the scFv is fused to the transmembrane domain and then to the intracellular signaling domain. In certain embodiments, the CAR is selected to have high binding affinity or avidity for the antigen. The term “B cell antigen,” as used herein, refer to a molecule (e.g., a protein, a carbohydrate, or a lipid) that is expressed on the surface of a B cell. Non-limiting examples of B cell antigens include CD5, CD10, CD19, CD20, CD21, CD22, CD23, CD24, CD25, CD27, CD30, CD34, CD37, CD38, CD40, CD53, CD69, CD72, CD73, CD74, CD75, CD77, CD79a, CD79b, CD80, CD81, CD82, CD83, CD84, CD85, CD86, CD123, CD135, CD138, CD179, CD269, Flt3, ROR1, BCMA, FcRn5, FcRn2, CS-1, CXCR4, 5, 7, IL-7 / 3R, IL7 / 4 / 3R, and IL4R. In certain embodiments, the B cell antigen is selected from CD19, CD20, CD22, FcRn5, FcRn2, BCMA, CS-1, or CD138. In certain embodiments, the B cell antigen is CD19. In certain embodiments, the B cell antigen is CD20. In certain embodiments, the B cell antigen is CD22. In certain embodiments, the B cell antigen is BCMA. In certain embodiments, the B cell antigen is FcRn5. As used herein, the term “substantially identical” or “substantially homologous” refers to a polypeptide or a nucleic acid molecule exhibiting at least about 50% identical or homologous to a reference amino acid sequence (for example, any of the amino acid sequences described herein) or a reference nucleic acid sequence (for example, any of the nucleic acid sequences described herein). In certain embodiments, such a sequence is at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99%, or at least about 100% identical or homologous to the amino acid sequence or the nucleic acid sequence used for comparison. Sequence identity can be measured by using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis. 53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, ACTIVE 511192992.1 11 072734.1806 PATENT asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e-3 and e-100 indicating a closely related sequence. The percent homology between two amino acid sequences can be determined using the algorithm of E. Meyers and W. Miller (Comput. Appl. Biosci., 4:11-17 (1988)) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. In addition, the percent homology between two amino acid sequences can be determined using the Needleman and Wunsch (J. Mol. Biol. 48:444-453 (1970)) algorithm which has been incorporated into the GAP program in the GCG software package (available at www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. Additionally or alternatively, the amino acids sequences of the presently disclosed subject matter can further be used as a “query sequence” to perform a search against public databases to, for example, identify related sequences. Such searches can be performed using the XBLAST program (version 2.0) of Altschul, et al. (1990) J. Mol. Biol.215:403-10. BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to the specified sequences (e.g., heavy and light chain variable region sequences) disclosed herein. To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997) Nucleic Acids Res. 25(17):3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used. As used herein, the term “a conservative sequence modification” refers to an amino acid modification that does not significantly affect or alter the binding characteristics of the presently disclosed antigen recognizing receptors (e.g., the extracellular antigen-binding domain of the CAR) comprising the amino acid sequence. Conservative modifications can include amino acid substitutions, additions and deletions. Modifications can be introduced into the extracellular antigen-binding domain of the presently disclosed CAR by standard techniques known in the art, such as site-directed mutagenesis and PCR-mediated mutagenesis. Amino acids can be classified into groups according to their physicochemical properties such as charge and polarity. Conservative amino acid substitutions are ones in which the amino acid residue is replaced with an amino acid within the same group. For example, amino acids can be classified by charge: positively-charged amino acids include lysine, arginine, histidine, negatively-charged amino acids include aspartic acid, glutamic acid, neutral charge amino acids include alanine, asparagine, cysteine, glutamine, glycine, isoleucine, leucine, methionine, ACTIVE 511192992.1 12 072734.1806 PATENT phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine. In addition, amino acids can be classified by polarity: polar amino acids include arginine (basic polar), asparagine, aspartic acid (acidic polar), glutamic acid (acidic polar), glutamine, histidine (basic polar), lysine (basic polar), serine, threonine, and tyrosine; non-polar amino acids include alanine, cysteine, glycine, isoleucine, leucine, methionine, phenylalanine, proline, tryptophan, and valine. Thus, one or more amino acid residues within a CDR region can be replaced with other amino acid residues from the same group and the altered antibody can be tested for retained function (i.e., the functions set forth in (c) through (l) above) using the functional assays described herein. In certain embodiments, no more than one, no more than two, no more than three, no more than four, no more than five residues within a specified sequence or a CDR region are altered. By “disease” is meant any condition, disease or disorder that damages or interferes with the normal function of a cell, tissue, or organ, e.g., neoplasm, and pathogen infection of cell. By “effective amount” is meant an amount sufficient to have a therapeutic effect. In certain embodiments, an “effective amount” is an amount sufficient to arrest, ameliorate, or inhibit the continued proliferation, growth, or metastasis (e.g., invasion, or migration) of a neoplasm. By “endogenous” is meant a nucleic acid molecule or polypeptide that is normally expressed in a cell or tissue. By “exogenous” is meant a nucleic acid molecule or polypeptide that is not endogenously present in a cell. The term “exogenous” would therefore encompass any recombinant nucleic acid molecule or polypeptide expressed in a cell, such as foreign, heterologous, and over-expressed nucleic acid molecules and polypeptides. By “exogenous” nucleic acid is meant a nucleic acid not present in a native wild-type cell; for example, an exogenous nucleic acid may vary from an endogenous counterpart by sequence, by position / location, or both. For clarity, an exogenous nucleic acid may have the same or different sequence relative to its native endogenous counterpart; it may be introduced by genetic engineering into the cell itself or a progenitor thereof, and may optionally be linked to alternative control sequences, such as a non-native promoter or secretory sequence. By “increase” is meant to alter positively by at least about 5%. An alteration may be by about 5%, about 10%, about 25%, about 30%, about 50%, about 75%, about 100% or more. By “reduce” is meant to alter negatively by at least about 5%. An alteration may be by about 5%, about 10%, about 25%, about 30%, about 50%, about 75%, or even by about 100%. ACTIVE 511192992.1 13 072734.1806 PATENT The terms “isolated,” “purified,” or “biologically pure” refer to material that is free to varying degrees from components which normally accompany it as found in its native state. “Isolate” denotes a degree of separation from original source or surroundings. “Purify” denotes a degree of separation that is higher than isolation. A “purified” or “biologically pure” protein is sufficiently free of other materials such that any impurities do not materially affect the biological properties of the protein or cause other adverse consequences. That is, a nucleic acid or peptide is purified if it is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Purity and homogeneity are typically determined using analytical chemistry techniques, for example, polyacrylamide gel electrophoresis or high-performance liquid chromatography. The term “purified” can denote that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. For a protein that can be subjected to modifications, for example, phosphorylation or glycosylation, different modifications may give rise to different isolated proteins, which can be separately purified. By “isolated cell” is meant a cell that is separated from the molecular and / or cellular components that naturally accompany the cell. The term “antigen-binding domain” as used herein refers to a domain capable of specifically binding a particular antigenic determinant or set of antigenic determinants present on a cell. By “neoplasm” or “malignancy” is meant a disease characterized by the pathological proliferation of a cell or tissue and its subsequent migration to or invasion of other tissues or organs. Neoplasm growth is typically uncontrolled and progressive, and occurs under conditions that would not elicit, or would cause cessation of, multiplication of normal cells. Neoplasm can affect a variety of cell types, tissues, or organs, including but not limited to an organ selected from bladder, bone, brain, breast, cartilage, glia, esophagus, fallopian tube, gallbladder, heart, intestines, kidney, liver, lung, lymph node, nervous tissue, ovaries, pancreas, prostate, skeletal muscle, skin, spinal cord, spleen, stomach, testes, thymus, thyroid, trachea, urogenital tract, ureter, urethra, uterus, and vagina, or a tissue or cell type thereof. Neoplasms include cancers, such as sarcomas, carcinomas, or plasmacytomas (malignant tumor of the plasma cells). In certain embodiments, the neoplasm is cancer. By “specifically binds” is meant a polypeptide or a fragment thereof that recognizes and binds to a biological molecule of interest (e.g., a polypeptide), but which does not substantially recognize and bind other molecules in a sample, for example, a biological sample, which naturally includes a presently disclosed polypeptide. ACTIVE 511192992.1 14 072734.1806 PATENT The term “tumor antigen” as used herein refers to an antigen (e.g., a polypeptide) that is uniquely or differentially expressed on a tumor cell compared to a normal or non- neoplastic cell. In certain embodiments, a tumor antigen includes any polypeptide expressed by a tumor that is capable of activating or inducing an immune response via an antigen recognizing receptor or capable of suppressing an immune response via receptor-ligand binding. The terms “comprises”, “comprising”, and are intended to have the broad meaning ascribed to them in U.S. Patent Law and can mean “includes”, “including” and the like. As used herein, “treatment” refers to clinical intervention in an attempt to alter the disease course of the individual or cell being treated, and can be performed either for prophylaxis or during the course of clinical pathology. Therapeutic effects of treatment include, without limitation, preventing occurrence or recurrence of disease, alleviation of symptoms, diminishment of any direct or indirect pathological consequences of the disease, preventing metastases, decreasing the rate of disease progression, amelioration or palliation of the disease state, and remission or improved prognosis. By preventing progression of a disease or disorder, a treatment can prevent deterioration due to a disorder in an affected or diagnosed subject or a subject suspected of having the disorder, but also a treatment may prevent the onset of the disorder or a symptom of the disorder in a subject at risk for the disorder or suspected of having the disorder. An “individual” or “subject” herein is a vertebrate, such as a human or non-human animal, for example, a mammal. Mammals include, but are not limited to, humans, primates, farm animals, sport animals, rodents and pets. Non-limiting examples of non-human animal subjects include rodents such as mice, rats, hamsters, and guinea pigs; rabbits; dogs; cats; sheep; pigs; goats; cattle; horses; and non-human primates such as apes and monkeys. The term “immunocompromised” as used herein refers to a subject who has an immunodeficiency. The subject is very vulnerable to opportunistic infections, infections caused by organisms that usually do not cause disease in a person with a healthy immune system, but can affect people with a poorly functioning or suppressed immune system. As used herein, “a functional fragment” of a molecule or polypeptide includes a fragment of the molecule or polypeptide that retains at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% of the primary function of the molecule or polypeptide. Other aspects of the presently disclosed subject matter are described in the following disclosure and are within the ambit of the presently disclosed subject matter. ACTIVE 511192992.1 15 072734.1806 PATENT 2. Cells The presently disclosed subject matter provides cells comprising an antigen- recognizing receptor targeting a B cell antigen (e.g., CD19, FcRL5, etc.). In certain embodiments, the presently disclosed subject matter provides cells comprising an antigen- recognizing receptor targeting CD19. In certain embodiments, the presently disclosed subject matter provides cells comprising an antigen-recognizing receptor targeting FcRL5. In certain embodiments, the cell is selected from the group consisting of cells of lymphoid lineage and cells of myeloid lineage. In certain embodiments, the cell is an immunoresponsive cell. In certain embodiments, the immunoresponsive cell is a cell of lymphoid lineage. In certain embodiments, the cell is a cell of the lymphoid lineage. Cells of the lymphoid lineage can provide production of antibodies, regulation of cellular immune system, detection of foreign agents in the blood, detection of cells foreign to the host, and the like. Non-limiting examples of cells of the lymphoid lineage include T cells, Natural Killer (NK) cells, B cells, dendritic cells, stem cells from which lymphoid cells may be differentiated. In certain embodiments, the stem cell is a pluripotent stem cell (e.g., embryonic stem cell). In certain embodiments, the cell is a T cell. T cells can be lymphocytes that mature in the thymus and are chiefly responsible for cell-mediated immunity. T cells are involved in the adaptive immune system. The T cells of the presently disclosed subject matter can be any type of T cells, including, but not limited to, helper T cells, cytotoxic T cells, memory T cells (including central memory T cells, stem-cell-like memory T cells (or stem-like memory T cells), and two types of effector memory T cells: e.g., TEM cells and TEMRA cells, Regulatory T cells (also known as suppressor T cells), tumor-infiltrating lymphocyte (TIL), Natural Killer T cells, Mucosal associated invariant T cells, and γδ T cells. Cytotoxic T cells (CTL or killer T cells) are a subset of T lymphocytes capable of inducing the death of infected somatic or tumor cells. A patient’s own T cells may be genetically modified to target specific antigens through the introduction of an antigen-recognizing receptor, e.g., a CAR or a TCR. The T cell can be a CD4+T cell or a CD8+T cell. In certain embodiments, the T cell is a CD4+T cell. In certain embodiments, the T cell is a CD8+T cell. In certain embodiments, the CD8+T cell is CD4 independent. In certain embodiments, the T cell is derived from an induced pluripotent stem cell (iPSC). In certain embodiments, the T cell is a CD8+T cell that is CD4 independent, and the CD8+T cell is derived from an iPSC. In certain embodiments, the T cell is a CD62L+T cell. In certain embodiments, the T cell is a CD45RA+T cell. In certain embodiments, the T cell is a CD62L+ / CD45RA+T cell. ACTIVE 511192992.1 16 072734.1806 PATENT In certain embodiments, the cell is a NK cell. Natural Killer (NK) cells can be lymphocytes that are part of cell-mediated immunity and act during the innate immune response. NK cells do not require prior activation in order to perform their cytotoxic effect on target cells. Types of human lymphocytes of the presently disclosed subject matter include, without limitation, peripheral donor lymphocytes, e.g., those disclosed in Sadelain, M., et al.2003 Nat Rev Cancer 3:35-45 (disclosing peripheral donor lymphocytes genetically modified to express CARs), in Morgan, R.A., et al. 2006 Science 314:126-129 (disclosing peripheral donor lymphocytes genetically modified to express a full-length tumor antigen-recognizing T cell receptor complex comprising the ^ and β heterodimer), in Panelli, M.C., et al.2000 J Immunol 164:495-504; Panelli, M.C., et al. 2000 J Immunol 164:4382-4392 (disclosing lymphocyte cultures derived from tumor infiltrating lymphocytes (TILs) in tumor biopsies), and in Dupont, J., et al.2005 Cancer Res 65:5417-5427; Papanicolaou, G.A., et al.2003 Blood 102:2498-2505 (disclosing selectively in vitro-expanded antigen-specific peripheral blood leukocytes employing artificial antigen-presenting cells (AAPCs) or pulsed dendritic cells). In certain embodiments, the cell (e.g., T cell) is autologous. In certain embodiments, the cell (e.g., T cell) is non-autologous. In certain embodiments, the cell (e.g., T cell) is allogeneic. In certain embodiments, the allogeneic cell is HLA-negative or HLA-class I negative. In certain embodiments, the cell (e.g., T cell) is derived in vitro from an engineered progenitor or stem cell. In certain embodiments, the cell is a cell of the myeloid lineage. Non-limiting examples of cells of the myeloid lineage include monocytes, macrophages, neutrophils, basophils, eosinophils, erythrocytes, megakaryocytes, and stem cells from which myeloid cells may be differentiated. In certain embodiments, the stem cell is a pluripotent stem cell (e.g., an embryonic stem cell or an induced pluripotent stem cell). 2.1. Chimeric Antigen Receptors (CARs) In certain embodiments, the antigen-recognizing receptor is a chimeric receptor. In certain embodiments, the chimeric receptor is a chimeric antigen receptor (CAR). CARs are engineered receptors, which graft or confer a specificity of interest onto an immune effector cell. CARs can be used to graft the specificity of a monoclonal antibody onto a T cell; with transfer of their coding sequence facilitated by retroviral vectors. ACTIVE 511192992.1 17 072734.1806 PATENT There are three generations of CARs. “First generation” CARs are typically composed of an extracellular antigen-binding domain (e.g., an scFv) that binds to a target antigen, and an intracellular signaling domain. In certain embodiments, the CAR further comprises a transmembrane domain. “First generation” CARs can provide de novo antigen recognition and cause activation of both CD4+and CD8+T cells through their CD3ζ chain signaling domain in a single fusion molecule, independent of HLA-mediated antigen presentation. “Second generation” CARs include a signaling domain of a co-stimulatory molecule (e.g., CD28, 4- 1BB, ICOS, OX40, CD27, CD40,NKG2D, DAP-10, CD2, CD150, CD226) to the intracellular signaling domain of the CAR to provide co-stimulation signals to the cell (e.g., T cell or NK cell). “Second generation” CARs comprise those that provide both co-stimulation (e.g., CD28 or 4-1BB) and activation (CD3ζ). “Third generation” CARs comprise those that provide multiple co-stimulation (e.g., CD28 and 4-1BB) and activation (CD3ζ). In certain embodiments, the antigen-recognizing receptor is a CAR comprising an extracellular antigen-binding domain that binds to a B cell antigen, and an intracellular signaling domain. In certain embodiments, the CAR further comprises a transmembrane domain. In certain embodiments, the CAR further comprises a hinger / spacer region. In certain embodiments, the antigen-recognizing receptor is a CAR comprising an extracellular antigen-binding domain that binds to CD19, and an intracellular signaling domain. In certain embodiments, the CAR further comprises a transmembrane domain. In certain embodiments, the CAR further comprises a hinger / spacer region. In certain embodiments, the antigen-recognizing receptor is a CAR comprising an extracellular antigen-binding domain that binds to FcRL5, and an intracellular signaling domain. In certain embodiments, the CAR further comprises a transmembrane domain. In certain embodiments, the CAR further comprises a hinger / spacer region. 2.1.1. Extracellular Antigen-Binding Domain In certain embodiments, the extracellular antigen-binding domain of the CAR (for example, an scFv) binds to the B cell antigen with a dissociation constant (KD) of about 5 × 10-7M or less, about 1 × 10-7M or less, about 5 × 10-8M or less, about 1 × 10-8M or less, about 5 × 10-9M or less, or about 1 × 10-9M or less, or about 1 × 10-10M or less. In certain embodiments, the extracellular antigen-binding domain of the CAR (for example, an scFv) binds to the antigen with a KDof about 1 × 10-8M or less. Binding of the extracellular antigen-binding domain (for example, in an scFv) can be confirmed by, for example, enzyme-linked immunosorbent assay (ELISA), radioimmunoassay ACTIVE 511192992.1 18 072734.1806 PATENT (RIA), FACS analysis, bioassay (e.g., growth inhibition), or Western Blot assay. Each of these assays generally detect the presence of protein-antibody complexes of particular interest by employing a labeled reagent (e.g., an antibody, or an scFv) specific for the complex of interest. For example, the scFv can be radioactively labeled and used in a radioimmunoassay (RIA) (see, for example, Weintraub, B., Principles of Radioimmunoassays, Seventh Training Course on Radioligand Assay Techniques, The Endocrine Society, March, 1986, which is incorporated by reference herein). The radioactive isotope can be detected by such means as the use of a γ counter or a scintillation counter or by autoradiography. In certain embodiments, the extracellular antigen-binding domain of the CAR is labeled with a fluorescent marker. Non- limiting examples of fluorescent markers include green fluorescent protein (GFP), blue fluorescent protein (e.g., EBFP, EBFP2, Azurite, and mKalama1), cyan fluorescent protein (e.g., ECFP, Cerulean, and CyPet), and yellow fluorescent protein (e.g., YFP, Citrine, Venus, and YPet). The extracellular antigen-binding domain can comprise or be an scFv, a Fab (which is optionally crosslinked), or a F(ab)2. In certain embodiments, any of the foregoing molecules may be comprised in a fusion protein with a heterologous sequence to form the extracellular antigen-binding domain. In certain embodiments, the extracellular antigen-binding domain comprises or is an scFv. In certain embodiments, the scFv is a human scFv. In certain embodiments, the scFv is a humanized scFv. In certain embodiments, the scFv is a murine scFv. 2.1.1.1. Exemplary Extracellular Antigen-Binding Domains In certain embodiments, the antigen-recognizing receptor is a CAR comprising an extracellular antigen-binding domain that binds to CD19. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a heavy chain variable region (VH) comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 70 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 71 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72 or a conservative modification thereof. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VHcomprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 70, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 71, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72. SEQ ID NOs: 70-72 are provided in Table 1 below. ACTIVE 511192992.1 19 072734.1806 PATENT In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a light chain variable region (VL) comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 73 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 74 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 75 or a conservative modification thereof. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VLcomprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 75. SEQ ID NOs: 73-75 are provided in Table 1 below. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 70 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 71 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72, a conservative modification thereof; a VL comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 73 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 74 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 75 or a conservative modification thereof. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VHcomprising a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 70, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 71, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72; and a VL comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 75. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 76 or SEQ ID NO: 77. For example, the extracellular antigen-binding domain of the antigen-recognizing receptor comprises a VHcomprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% homologous ACTIVE 511192992.1 20 072734.1806 PATENT or identical to the amino acid sequence set forth in SEQ ID NO: 76 or SEQ ID NO: 77. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 76 or SEQ ID NO: 77. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VL comprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 78 or SEQ ID NO: 79. For example, the extracellular antigen-binding domain of the CAR comprises a VL comprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 78 or SEQ ID NO: 79. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VL comprising the amino acid sequence set forth in SEQ ID NO: 78 or SEQ ID NO: 79. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 76 or SEQ ID NO: 77, and a VL comprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 78 or SEQ ID NO: 79. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 76 or SEQ ID NO: 77. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VL comprising the amino acid sequence set forth in SEQ ID NO: 78 or SEQ ID NO: 79. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises VHcomprising the amino acid sequence set forth in SEQ ID NO: 76 or SEQ ID NO: 77 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 78 or SEQ ID NO: 79. In certain embodiments, the extracellular antigen-binding domain of the CAR is an scFv that comprises or consists of the amino acid sequence set forth in SEQ ID NO: 80. SEQ ID NOs: 76-80 are provided in the following Table 1. In certain embodiments, the VH and VL are linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, or SEQ ACTIVE 511192992.1 21 072734.1806 PATENTID NO: 6. In certain embodiments, the CDRs regions / sequences disclosed herein aredelineated using the Kabat system (Swindells et al., J Mol Biol.2017 Feb 3;429(3):356-364). Table 1 CDRS 1 2 3 V GYAFSS [SEQ ID NO: YPGDGD [SEQ ID KTISSVVDF [SEQ ID 70] NO: 71] NO: 72] V KASQNVGTNVA [SEQ SATYRN [SEQ ID QQYNRYPYT [SEQ ID ID NO: 73] NO: 74] NO: 75] FULL V EVKLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDT NYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYFCARKTISSVVDFYFDYWGQGT TVTVSS[SEQ ID NO: 76] FULL V EVKLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDT V2 NYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYFCARKTISSVVDFYFDYWGQGT TVTV [SEQ ID NO: 77] FULL V DIELTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGV PDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYTSGGGTKLEIKR [SEQ ID NO: 78] FULL V DIELTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGV V2 PDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYTSGGGTKLEI [SEQ ID NO: 79] SCFV MALPVTALLLPLALLLHAEVKLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQR PGQGLEWIGQIYPGDGDTNYNGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYFCAR KTISSVVDFYFDYWGQGTTVTVSSGGGGSGGGGSGGGGSDIELTQSPKFMSTSVGDRV SVTCKASQNVGTNVAWYQQKPGQSPKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITN VQSKDLADYFCQQYNRYPYTSGGGTKLEIKR[SEQ ID NO: 80] Additional examples of antigen-recognizing receptors comprising an extracellular antigen-binding domain that binds to CD19 can be found in International Patent Publication No. WO2014153270, U.S. Patent No.11,578,126, U.S. Patent No.11,034,763, U.S. Patent No. 11,149,076, International Patent Publication No. WO2021217130, and International Patent Publication No. WO2015157252, the contents of each of which are incorporated by reference in their entirety. In certain embodiments, the antigen-recognizing receptor is a CAR comprising an extracellular antigen-binding domain that binds to Fc Receptor-like 5 (FcRL5). In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a heavy chain variable region (VH) comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83 or a conservative modification thereof. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VHcomprising a CDR1 comprising the amino acid sequence ACTIVE 511192992.1 22 072734.1806 PATENT set forth in SEQ ID NO: 81, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83. SEQ ID NOs: 81-83 are provided in Table 2 below. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a light chain variable region (VL) comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86 or a conservative modification thereof. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VLcomprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86. SEQ ID NOs: 84-86 are provided in Table 2 below. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 81 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83, a conservative modification thereof; a VL comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84 or a conservative modification thereof, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85 or a conservative modification thereof, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86 or a conservative modification thereof. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 81, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83; and a VL comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VHcomprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 87. For example, the extracellular antigen-binding domain of the antigen-recognizing receptor comprises a VHcomprising an amino acid sequence ACTIVE 511192992.1 23 072734.1806 PATENT that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 87. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 87. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VL comprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 88. For example, the extracellular antigen-binding domain of the CAR comprises a VLcomprising an amino acid sequence that is about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 88. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VL comprising the amino acid sequence set forth in SEQ ID NO: 88. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 87, and a VLcomprising an amino acid sequence that is at least about 80% (e.g., at least about 85%, at least about 90%, or at least about 95%) homologous or identical to the amino acid sequence set forth in SEQ ID NO: 88. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VHcomprising the amino acid sequence set forth in SEQ ID NO: 87. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VL comprising the amino acid sequence set forth in SEQ ID NO: 88. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises VHcomprising the amino acid sequence set forth in SEQ ID NO: 87 and a VL comprising the amino acid sequence set forth in SEQ ID NO: 88. SEQ ID NOs: 87 and 88 are provided in the following Table 2. In certain embodiments, the VHand VLare linked via a linker. In certain embodiments, the linker comprises the amino acid sequence set forth in SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQID NO: 5, or SEQ ID NO: 6. In certain embodiments, the CDRs regions / sequences disclosedherein are delineated using the Kabat system (Swindells et al., J Mol Biol. 2017 Feb 3;429(3):356-364). ACTIVE 511192992.1 24 072734.1806 PATENT Table 2 CDRS 1 2 3 V SYEMN [SEQ ID NO: YISSSGSTIYYADSVK WDYGMDV [SEQ ID NO: 81] G [SEQ ID NO: 82] 83] V TRSSGSIASNYVQ [SEQ EDNQRPS [SEQ ID QSYDSSNVV [SEQ ID ID NO: 84] NO: 85] NO: 86] FULL V EVQLVESGGGLVQPGGSLRLSCAASGFTFSSYEMNWVRQAPGKGLEWVSYISSSGSTI YYADSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARWDYGMDVWGQGTTVTVSS [SEQ ID NO: 87] FULL V NFMLTQPHSVSESPGKTVTISCTRSSGSIASNYVQWYQQRPGSAPTTVIYEDNQRPSG VPDRFSGSIDSSSNSASLTISGLKTEDEADYYCQSYDSSNVVFGGGTKVTVLG [SEQ ID NO: 88] Additional examples of antigen-recognizing receptors comprising an extracellular antigen-binding domain that binds to FcRL5 can be found in International Patent Publication No. WO2016090337, the contents of which are incorporated by reference in their entirety. The VHand / or VLamino acid sequences having at least about 80%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% (e.g., about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, or about 99%) homology or identity to a specific sequence (e.g., SEQ ID NOs: 76, 77, 78, 79, 87, and 88) may contain substitutions (e.g., conservative substitutions), insertions, or deletions relative to the specified sequence(s), but retain the ability to bind to CD19 or FcRL5. In certain embodiments, a total of 1 to 10 amino acids are substituted, inserted, and / or deleted in a specific sequence (e.g., SEQ ID NOs: 76, 77, 78, 79, 87, and 88). In certain embodiments, substitutions, insertions, or deletions occur in regions outside the CDRs (e.g., in the FRs) of the extracellular antigen-binding domain. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises VH and / or VL sequences selected from SEQ ID NOs: 76, 77, 78, 79, 87, and 88, including post-translational modifications of that sequence (SEQ ID NOs: 76, 77, 78, 79, 87, and 88). In addition, the extracellular antigen-binding domain of the CAR can comprise a leader or a signal peptide that directs the nascent protein into the endoplasmic reticulum. Signal peptide or leader can be essential if the CAR is to be glycosylated and anchored in the cell membrane. The signal sequence or leader can be a peptide sequence (about 5, about 10, about 15, about 20, about 25, or about 30 amino acids long) present at the N-terminus of newly synthesized proteins that directs their entry to the secretory pathway. In certain embodiments, ACTIVE 511192992.1 25 072734.1806 PATENT the signal peptide is covalently joined to the 5’ terminus (N-terminus) of the extracellular antigen-binding domain of the CAR. Exemplary leader sequences include, but is not limited to, a human IL-2 signal sequence (e.g., a human IL-2 signal sequence comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 7), a mouse IL-2 signal sequence (e.g., a mouse IL-2 signal sequence comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 8); a human kappa leader sequence (e.g., a human kappa leader sequence comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 9), a mouse kappa leader sequence (e.g., a mouse kappa leader sequence comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 10); a human CD8 leader sequence (e.g., a human CD8 leader sequence comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 11); a truncated human CD8 signal peptide (e.g., a truncated human CD8 signal peptide comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 12); a human albumin signal sequence (e.g., a human albumin signal sequence comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 13); and a human prolactin signal sequence (e.g., a human prolactin signal sequence comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 14). SEQ ID NO: 7-14 are provided below. MYRMQLLSCIALSLALVTNS [SEQ ID NO: 7] MYSMQLASCVTLTLVLLVNS [SEQ ID NO: 8] METPAQLLFLLLLWLPDTTG [SEQ ID NO: 9] METDTLLLWVLLLWVPGSTG [SEQ ID NO: 10] MALPVTALLLPLALLLHAARP [SEQ ID NO: 11] MALPVTALLLPLALLLHA [SEQ ID NO: 12] MKWVTFISLLFSSAYS [SEQ ID NO: 13] MDSKGSSQKGSRLLLLLVVSNLLLCQGVVS [SEQ ID NO: 14] In certain embodiments, the signal peptide comprises a CD8 polypeptide, e.g., the CAR comprises a truncated CD8 signal peptide. In certain embodiments, the signal peptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 12. 2.1.2. Transmembrane Domain and Hinge / Spacer Region In certain embodiments, the antigen-recognizing receptor is a CAR that comprises a transmembrane domain. Different transmembrane domains result in different receptor stability. After antigen recognition, receptors cluster and a signal is transmitted to the cell. In accordance with the presently disclosed subject matter, the transmembrane domain of the ACTIVE 511192992.1 26 072734.1806 PATENT antigen-recognizing receptor can comprise a native or modified transmembrane domain of a CD8 polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD40 polypeptide, a 4-1BB polypeptide, an OX40 polypeptide, a CD84 polypeptide, a CD166 polypeptide, a CD8a polypeptide, a CD8b polypeptide, an ICOS polypeptide, an ICAM-1 polypeptide, a CTLA-4 polypeptide, a CD27 polypeptide, a CD40 polypeptide, a NKG2D polypeptide, a synthetic polypeptide (not based on a protein associated with the immune response), or a combination thereof. In certain embodiments, the transmembrane domain of the CAR comprises a CD28 polypeptide (e.g., the transmembrane domain of CD28 or a portion thereof). In certain embodiments, the transmembrane domain of the CAR comprises a transmembrane domain of human CD28 or a portion thereof. In certain embodiments, the CD28 polypeptide comprises or consists of an amino acid sequence that is a consecutive portion of the amino acid sequence having a NCBI Reference No: NP_006130 (SEQ ID NO: 15), which is at least about 20, or at least about 25, or at least about 30, and / or up to about 220 amino acids in length. In certain embodiments, the CD28 polypeptide comprises or consists of an amino acid sequence of amino acids 1 to 220, 1 to 50, 50 to 100, 100 to 150, 114 to 220, 150 to 200, 153 to 179, or 200 to 220 of SEQ ID NO: 15. In certain embodiments, the transmembrane domain of the CAR comprises a CD28 polypeptide that comprises or consists of amino acids 153 to 179 of SEQ ID NO: 15. SEQ ID NO: 15 is provided below. MLRLLLALNLFPSIQVTGNKILVKQSPMLVAYDNAVNLSCKYSYNLFSREFRASLHKGLDSAVEVCVV YGNYSQQLQVYSKTGFNCDGKLGNESVTFYLQNLYVNQTDIYFCKIEVMYPPPYLDNEKSNGTIIHVK GKHLCPSPLFPGPSKPFWVLVVVGGVLACYSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRK HYQPYAPPRDFAAYRS [SEQ ID NO: 15] In certain embodiments, the antigen-recognizing receptor is a CAR that further comprises a hinge / spacer region that links the extracellular antigen-binding domain to the transmembrane domain. The hinge / spacer region can be flexible enough to allow the antigen binding domain to orient in different directions to facilitate antigen recognition. In certain embodiments, the hinge / spacer region of the CAR can comprise a native or modified hinge region of a CD8 polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD40 polypeptide, a 4-1BB polypeptide, an OX40 polypeptide, a CD84 polypeptide, a CD166 polypeptide, a CD8a polypeptide, a CD8b polypeptide, an ICOS polypeptide, an ICAM-1 polypeptide, a CTLA-4 polypeptide, a CD27 polypeptide, a CD40 polypeptide, a NKG2D polypeptide, a synthetic polypeptide (not based on a protein associated with the immune response), or a combination thereof. The hinge / spacer region can be the hinge region from IgG1, or the ACTIVE 511192992.1 27 072734.1806 PATENT CH2CH3region of immunoglobulin and portions of CD3, a portion of a CD28 polypeptide (e.g., a portion of SEQ ID NO: 15), a portion of a CD8 polypeptide, or a synthetic spacer sequence. In certain embodiments, the antigen-recognizing receptor is a CAR that further comprises a hinge / spacer region comprising a native or modified hinge region of a CD28 polypeptide. In certain embodiments, the hinge / spacer region of the first antigen-recognizing receptor (e.g., a CAR) comprises a CD28 polypeptide comprising or consisting of amino acids 114 to 152 of SEQ ID NO: 15. In certain embodiments, the hinge / spacer region is positioned between the extracellular antigen-binding domain and the transmembrane domain. In certain embodiments, the hinge / spacer region comprises a CD8 polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD4 polypeptide, a 4-1BB polypeptide, an OX40 polypeptide, a CD166 polypeptide, a CD8a polypeptide, a CD8b polypeptide, an ICOS polypeptide, an ICAM-1 polypeptide, a CTLA-4 polypeptide, a CD27 polypeptide, a CD40 polypeptide, a NKG2D polypeptide, a synthetic polypeptide (not based on a protein associated with the immune response), or a combination thereof. In certain embodiments, the transmembrane domain comprises a CD8 polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD4 polypeptide, a 4-1BB polypeptide, an OX40 polypeptide, a CD166 polypeptide, a CD8a polypeptide, a CD8b polypeptide, an ICOS polypeptide, an ICAM-1 polypeptide, a CTLA-4 polypeptide, a CD27 polypeptide, a CD40 polypeptide, a NKG2D polypeptide, a synthetic polypeptide (not based on a protein associated with the immune response), or a combination thereof. In certain embodiments, the transmembrane domain and the hinge / spacer region are derived from the same molecule. In certain embodiments, the transmembrane domain and the hinge / spacer region are derived from different molecules. In certain embodiments, the hinge / spacer region comprises a CD28 polypeptide and the transmembrane domain comprises a CD28 polypeptide. In certain embodiments, the hinge / spacer region comprises a CD28 polypeptide and the transmembrane domain comprises a CD28 polypeptide. In certain embodiments, the hinge / spacer region comprises a CD84 polypeptide and the transmembrane domain comprises a CD84 polypeptide. In certain embodiments, the hinge / spacer region comprises a CD166 polypeptide and the transmembrane domain comprises a CD166 polypeptide. In certain embodiments, the hinge / spacer region comprises a CD8α polypeptide and the transmembrane domain comprises a CD8α polypeptide. In certain embodiments, the hinge / spacer region comprises a CD8β polypeptide and the transmembrane domain comprises ACTIVE 511192992.1 28 072734.1806 PATENT a CD8β polypeptide. In certain embodiments, the hinge / spacer region comprises a CD28 polypeptide and the transmembrane domain comprises an ICOS polypeptide. 2.1.3. Intracellular Signaling Domain In certain embodiments, the antigen-recognizing receptor is a CAR that comprises an intracellular signaling domain. In certain embodiments, the intracellular signaling domain of the CAR comprises a CD3ζ polypeptide. CD3ζ can activate or stimulate a cell (e.g., a cell of the lymphoid lineage, e.g., a T-cell). Wild type (“native”) CD3ζ comprises three functional immunoreceptor tyrosine-based activation motifs (ITAMs), three functional basic-rich stretch (BRS) regions (BRS1, BRS2 and BRS3). CD3ζ transmits an activation signal to the cell (e.g., a cell of the lymphoid lineage, e.g., a T-cell) after antigen is bound. The intracellular signaling domain of the CD3ζ-chain is the primary transmitter of signals from endogenous TCRs. In certain embodiments, the intracellular signaling domain of the CAR comprises a native CD3ζ. In certain embodiments, the native CD3ζ comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% identical or homologous to the amino acid sequence having a NCBI Reference No: NP_932170 (SEQ ID NO: 16) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD3ζ polypeptide comprises or consists of an amino acid sequence that is a consecutive portion of SEQ ID NO: 16, which is at least about 20, or at least about 30, or at least about 40, or at least about 50, and up to about 164 amino acids in length. In certain embodiments, the native CD3ζ comprises or consists of the amino acid sequence of amino acids 1 to 164, 1 to 50, 50 to 100, 52 to 164, 100 to 150, or 150 to 164 of SEQ ID NO: 16. In certain embodiments, the intracellular signaling domain of the CAR comprises a native CD3ζ comprising or consisting of the amino acid sequence of amino acids 52 to 164 of SEQ ID NO: 16. SEQ ID NO: 16 is provided below: MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFIYGVILTALFLRVKFSRSADAPAYQQGQ NQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGK GHDGLYQGLSTATKDTYDALHMQALPPR [SEQ ID NO: 16] In certain embodiments, the native CD3ζ comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% identical or homologous to the amino acid sequence set forth in SEQ ID NO: 17. SEQ ID NO: 17 is provided below: ACTIVE 511192992.1 29 072734.1806 PATENT RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKDKMA EAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR [SEQ ID NO: 17] In certain embodiments, the intracellular signaling domain of the CAR comprises a modified CD3ζ polypeptide. In certain embodiments, the modified CD3ζ polypeptide comprises one, two or three ITAMs. In certain embodiments, the modified CD3ζ polypeptide comprises a native ITAM1. In certain embodiments, the native ITAM1 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 18. QNQLYNELNLGRREEYDVLDKR [SEQ ID NO: 18] An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 18 is set forth in SEQ ID NO: 19, which is provided below. CAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGA [SEQ ID NO: 19] In certain embodiments, the modified CD3ζ polypeptide comprises an ITAM1 variant comprising one or more loss-of-function mutations. In certain embodiments, the ITAM1 variant comprises or consists of two loss-of-function mutations. In certain embodiments, each of the one or more (e.g., two) loss of function mutations comprises a mutation of a tyrosine residue in ITAM1. In certain embodiments, the ITAM1 variant consists of two loss-of-function mutations. In certain embodiments, the ITAM1 variant comprises or consists of the amino acid sequence set forth in SEQ ID NO: 20, which is provided below. QNQLFNELNLGRREEFDVLDKR [SEQ ID NO: 20] An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 20 is set forth in SEQ ID NO: 21, which is provided below. CAGAACCAGCTCTTTAACGAGCTCAATCTAGGACGAAGAGAGGAGTTCGATGTTTTGGACAAGAGA [SEQ ID NO: 21] In certain embodiments, the modified CD3ζ polypeptide comprises a native ITAM2. In certain embodiments, the native ITAM2 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 22, which is provided below. QEGLYNELQKDKMAEAYSEIGMK [SEQ ID NO: 22] An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 22 is set forth in SEQ ID NO: 23, which is provided below. CAGGAAGGCCTGTACAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTACAGTGAGATTGGGATGAA A [SEQ ID NO: 23] ACTIVE 511192992.1 30 072734.1806 PATENT In certain embodiments, the modified CD3ζ polypeptide comprises an ITAM2 variant. In certain embodiments, the ITAM2 variant comprises or consists of one or more loss-of- function mutations. In certain embodiments, the ITAM2 variant comprises or consists of two loss-of-function mutations. In certain embodiments, each of the one or more (e.g., two) the loss of function mutations comprises a mutation of a tyrosine residue in ITAM2. In certain embodiments, the ITAM1 variant consists of two loss-of-function mutations. In certain embodiments, the ITAM2 variant comprises or consists of the amino acid sequence set forth in SEQ ID NO: 24, which is provided below. QEGLFNELQKDKMAEAFSEIGMK [SEQ ID NO: 24] An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 24 is set forth in SEQ ID NO: 25, which is provided below. CAGGAAGGCCTGTTCAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTTCAGTGAGATTGGGATGAA A [SEQ ID NO: 25] In certain embodiments, the modified CD3ζ polypeptide comprises a native ITAM3. In certain embodiments, the native ITAM3 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 26, which is provided below. HDGLYQGLSTATKDTYDALHMQ [SEQ ID NO: 26] An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 26 is set forth in SEQ ID NO: 27, which is provided below. CACGATGGCCTTTACCAGGGTCTCAGTACAGCCACCAAGGACACCTACGACGCCCTTCACATGCAG [SEQ ID NO: 27] In certain embodiments, the modified CD3ζ polypeptide comprises an ITAM3 variant. In certain embodiments, the ITAM3 variant comprises or consists of two loss-of-function mutations. In certain embodiments, each of the one or more (e.g., two) the loss of function mutations comprises a mutation of a tyrosine residue in ITAM3. In certain embodiments, the ITAM3 variant comprises or consists of two loss-of-function mutations. In certain embodiments, the ITAM3 variant comprises or consists of the amino acid sequence set forth in SEQ ID NO: 28, which is provided below. HDGLFQGLSTATKDTFDALHMQ [SEQ ID NO: 28] An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 28 is set forth in SEQ ID NO: 29, which is provided below. CACGATGGCCTTTTCCAGGGGCTCAGTACAGCCACCAAGGACACCTTCGACGCCCTTCACATGCAG [SEQ ID NO: 29] ACTIVE 511192992.1 31 072734.1806 PATENT Various modified CD3ζ polypeptides and CARs comprising modified CD3ζ polypeptides are disclosed in International Patent Application Publication No. WO2019 / 133969, which is incorporated by reference hereby in its entirety. In certain embodiments, the intracellular signaling domain of the CAR comprises a modified CD3ζ polypeptide comprising a native ITAM1, an ITAM2 variant comprising or consisting of one or more (e.g., two) loss-of-function mutations, and an ITAM3 variant comprising or consisting of one or more (e.g., two) loss-of-function mutations. In certain embodiments, the intracellular signaling domain of the CAR comprises a modified CD3ζ polypeptide comprising a native ITAM1, an ITAM2 variant consisting of two loss-of-function mutations, and an ITAM3 variant consisting of two loss-of-function mutations. In certain embodiments, the intracellular signaling domain of the CAR comprises a modified CD3ζ polypeptide comprising a native ITAM1 consisting of the amino acid sequence set forth in SEQ ID NO: 18, an ITAM2 variant consisting of the amino acid sequence set forth in SEQ ID NO: 24, and an ITAM3 variant consisting of the amino acid sequence set forth in SEQ ID NO: 28. In certain embodiments, the CAR is designated as “1XX”. In certain embodiments, the modified CD3ζ polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 30. SEQ ID NO: 30 is provided below: RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLFNELQKDKMA EAFSEIGMKGERRRGKGHDGLFQGLSTATKDTFDALHMQALPPR [SEQ ID NO: 30] In certain embodiments, the intracellular signaling domain of the CAR comprises a modified CD3ζ polypeptide comprising or consisting of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% identical to SEQ ID NO: 30 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 30 is set forth in SEQ ID NO: 31, which is provided below. AGAGTGAAGTTCAGCAGGAGCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGA GCTCAATCTAGGACGAAGAGAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGG GGGGAAAGCCGAGAAGGAAGAACCCTCAGGAAGGCCTGTTCAATGAACTGCAGAAAGATAAGATGGCG GAGGCCTTCAGTGAGATTGGGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTTCCA GGGGCTCAGTACAGCCACCAAGGACACCTTCGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC [SEQ ID NO: 31] ACTIVE 511192992.1 32 072734.1806 PATENT In certain embodiments, the intracellular signaling domain of the CAR further comprises at least one co-stimulatory signaling region. In certain embodiments, the at least one co-stimulatory region comprises a co-stimulatory molecule or a portion thereof. In certain embodiments, the at least one co-stimulatory region comprises at least an intracellular domain of at least one co-stimulatory molecule or a portion thereof. Non-limiting examples of costimulatory molecules include CD28, 4-1BB, OX40, CD27, CD40, CD154, CD97, CD11a / CD18, ICOS, DAP-10, CD2, CD150, CD226, and NKG2D. In certain embodiments, the intracellular signaling domain of the CAR comprises a co- stimulatory signaling region that comprises a CD28 polypeptide, e.g., an intracellular domain of CD28 or a portion thereof. In certain embodiments, the intracellular signaling domain of the CAR comprises a co-stimulatory signaling region that comprises an intracellular domain of human CD28 or a portion thereof. In certain embodiments, the CD28 polypeptide comprised in the co-stimulatory signaling region of the first antigen-recognizing receptor comprise or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% identical or homologous to the amino acid sequence set forth in SEQ ID NO: 15 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD28 polypeptide comprised in the co-stimulatory signaling region of the CAR comprises or consist of an amino acid sequence that is a consecutive portion of SEQ ID NO: 15, which is at least about 20, or at least about 30, or at least about 40, or at least about 50, and up to about 220 amino acids in length. Alternatively or additionally, in certain embodiments, the CD28 polypeptide comprised in the co-stimulatory signaling region of the CAR comprises or consists of amino acids 1 to 220, 1 to 50, 50 to 100, 100 to 150, 114 to 220, 150 to 200, 180 to 220, or 200 to 220 of SEQ ID NO: 15. In certain embodiments, the intracellular signaling domain of the CAR comprises a co-stimulatory signaling region that comprises a CD28 polypeptide comprising or consisting of amino acids 180 to 220 of SEQ ID NO: 15. An exemplary nucleic acid sequence encoding the amino acid sequence of amino acids 180 to 220 of SEQ ID NO: 15 is set forth in SEQ ID NO: 32, which is provided below. AGGAGTAAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCAC CCGCAAGCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCC [SEQ ID NO: 32] ACTIVE 511192992.1 33 072734.1806 PATENT In certain embodiments, the intracellular signaling domain of the first antigen- recognizing receptor comprises a co-stimulatory signaling region that comprises an intracellular domain of mouse CD28 or a portion thereof. In certain embodiments, the CD28 polypeptide comprised in the co-stimulatory signaling region comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% identical or homologous to the amino acid sequence having a NCBI Reference No: NP_031668.3 (or SEQ ID NO: 33) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD28 polypeptide comprised in the co-stimulatory signaling region of the CAR comprises or consists of an amino acid sequence that is a consecutive portion of SEQ ID NO: 33, which is at least about 20, or at least about 30, or at least about 40, or at least about 50, and up to 218 amino acids in length. In certain embodiments, the CD28 polypeptide comprised in the co-stimulatory signaling region of the CAR comprises or consists of the amino acid sequence of amino acids 1 to 218, 1 to 50, 50 to 100, 100 to 150, 150 to 218, 178 to 218, or 200 to 218 of SEQ ID NO: 33. In certain embodiments, the co-stimulatory signaling region of the CAR comprises a CD28 polypeptide that comprises or consists of amino acids 178 to 218 of SEQ ID NO: 33. SEQ ID NO: 33 is provided below. MTLRLLFLALNFFSVQVTENKILVKQSPLLVVDSNEVSLSCRYSYNLLAKEFRASLYKGVNSDVEVCV GNGNFTYQPQFRSNAEFNCDGDFDNETVTFRLWNLHVNHTDIYFCKIEFMYPPPYLDNERSNGTIIHI KEKHLCHTQSSPKLFWALVVVAGVLFCYGLLVTVALCVIWTNSRRNRLLQSDYMNMTPRRPGLTRKPY QPYAPARDFAAYRP [SEQ ID NO: 33] In certain embodiments, the intracellular signaling domain of the CAR comprises a co- stimulatory signaling region that comprises a 4-1BB polypeptide, e.g., an intracellular domain of 4-1BB or a portion thereof. In certain embodiments, the co-stimulatory signaling region comprises an intracellular domain of human 4-1BB or a portion thereof. In certain embodiments, the 4-1BB comprised in the co-stimulatory signaling region of the CAR comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% identical or homologous to the sequence having a NCBI Ref. No.: NP_001552 (SEQ ID NO: 34) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the 4-1BB comprised in the co-stimulatory signaling region of the CAR comprises or consists of an amino acid sequence that is a consecutive portion of SEQ ID NO: ACTIVE 511192992.1 34 072734.1806 PATENT 34, which is at least about 20, or at least about 30, or at least about 40, or at least about 50, and / or up to about 50, up to about 60, up to about 70, up to about 80, up to about 90, up to about 100, up to about 200, or up to about 255 amino acids in length. In certain embodiments, the co-stimulatory signaling region of the CAR comprises a 4-1BB polypeptide that comprises or consists of the amino acid sequence of amino acids 1 to 255, 1 to 50, 50 to 100, 100 to 150, 150 to 200, or 200 to 255 of SEQ ID NO: 34. In certain embodiments, the co-stimulatory signaling region of the CAR comprises a 4-1BB polypeptide comprising or consisting of the amino acid sequence of amino acids 214 to 255 of SEQ ID NO: 34. SEQ ID NO: 34 is provided below. MGNSCYNIVATLLLVLNFERTRSLQDPCSNCPAGTFCDNNRNQICSPCPPNSFSSAGGQRTCDICRQC KGVFRTRKECSSTSNAECDCTPGFHCLGAGCSMCEQDCKQGQELTKKGCKDCCFGTFNDQKRGICRPW TNCSLDGKSVLVNGTKERDVVCGPSPADLSPGASSVTPPAPAREPGHSPQIISFFLALTSTALLFLLF FLTLRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL [SEQ ID NO: 34] In certain embodiments, the intracellular signaling domain of the CAR comprises two co-stimulatory signaling regions, wherein the first co-stimulatory signaling region comprises an intracellular domain of a first co-stimulatory molecule or a portion thereof, and the second co-stimulatory signaling region comprises an intracellular domain of a second co-stimulatory molecule or a portion thereof. The first and second co-stimulatory molecules are independently selected from the group consisting of CD28, 4-1BB, OX40, CD27, CD40, CD154, CD97, CD11a / CD18, ICOS, DAP-10, CD2, CD150, CD226, and NKG2D. In certain embodiments, the intracellular signaling domain of the CAR comprises two co-stimulatory signaling regions, wherein the first co-stimulatory signaling region comprises an intracellular domain of CD28 or a portion thereof and the second co-stimulatory signaling region comprises an intracellular domain of 4-1BB or a portion thereof. In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain, ii) a transmembrane domain comprising a CD28 polypeptide (e.g., human CD28 polypeptide, e.g., a transmembrane domain of CD28 (e.g., human CD28) or a portion thereof), iii) a hinge / spacer region derived from a CD28 polypeptide (e.g., a human CD28 polypeptide), iv) an intracellular signaling domain comprising a) a native CD3ζ polypeptide, and b) a co-stimulatory signaling region comprising a CD28 polypeptide (e.g., a human CD28 polypeptide, e.g., an intracellular domain of CD28 (e.g., human CD28) of a portion thereof). In certain embodiments, the transmembrane domain comprises a CD28 polypeptide comprising or consisting of amino acids 153 to 179 of SEQ ID NO: 15. In certain embodiments, the hinge / spacer region comprises a CD28 polypeptide comprising or consisting ACTIVE 511192992.1 35 072734.1806 PATENT of amino acids 114 to 152 of SEQ ID NO: 15. In certain embodiments, the intracellular signaling domain comprises a native CD3ζ polypeptide comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 16, and a co-stimulatory signaling region comprising a CD28 polypeptide that comprises or consists of 180 to 220 of SEQ ID NO: 15. In certain embodiments, the CAR is designated as “28z”. In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain, ii) a transmembrane domain comprising a CD28 polypeptide (e.g., human CD28 polypeptide, e.g., a transmembrane domain of CD28 (e.g., human CD28) or a portion thereof), iii) a hinge / spacer region derived from a CD28 polypeptide (e.g., a human CD28 polypeptide), iv) an intracellular signaling domain comprising a) a modified CD3ζ polypeptide (e.g., a modified human CD3ζ polypeptide) comprising a native ITAM1, an ITAM2 variant consisting of two loss-of-function mutations, and an ITAM3 variant consisting of two loss-of-function mutations, and b) a co-stimulatory signaling region comprising a CD28 polypeptide (e.g., a human CD28 polypeptide, e.g., an intracellular domain of CD28 (e.g., human CD28) of a portion thereof). In certain embodiments, the transmembrane domain comprises a CD28 polypeptide comprising or consisting of amino acids 153 to 179 of SEQ ID NO: 15. In certain embodiments, the hinge / spacer region comprises a CD28 polypeptide comprising or consisting of amino acids 114 to 152 of SEQ ID NO: 15. In certain embodiments, the intracellular signaling domain comprises a modified CD3ζ polypeptide comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 30, and a co- stimulatory signaling region comprising a CD28 polypeptide that comprises or consists of 180 to 220 of SEQ ID NO: 15. In certain embodiments, the CAR is designated as “28z1xx”. In certain embodiments, the CAR (e.g., 28z1xx) is encoded by a nucleotide sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% identical to the nucleotide sequence set forth in SEQ ID NO: 35 or SEQ ID NO: 36. In certain embodiments, the CAR (e.g., 28z1xx) comprises the nucleotide sequence set forth in SEQ ID NO: 35 or SEQ ID NO: 36. SEQ ID NO: 35 and SEQ ID NO: 36 are provided below. ATTGAAGTTATGTATCCTCCTCCTTACCTAGACAATGAGAAGAGCAATGGAACCATTATCCATGTGAA AGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCCCTTTTGGGTGCTGGTGGTGG TTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCTTTATTATTTTCTGGGTGAGGAGT AAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAA GCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGA GCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGA ACTIVE 511192992.1 36 072734.1806 PATENT GAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAA GAACCCTCAGGAAGGCCTGTTCAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTTCAGTGAGATTG GGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTTCCAGGGTCTCAGTACAGCCACC AAGGACACCTTCGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC [SEQ ID NO: 35] ATTGAAGTTATGTATCCTCCTCCTTACCTAGACAATGAGAAGAGCAATGGAACCATTATCCATGTGAA AGGGAAACACCTTTGTCCAAGTCCCCTATTTCCCGGACCTTCTAAGCCCTTTTGGGTGCTGGTGGTGG TTGGTGGAGTCCTGGCTTGCTATAGCTTGCTAGTAACAGTGGCCTTTATTATTTTCTGGGTGAGGAGT AAGAGGAGCAGGCTCCTGCACAGTGACTACATGAACATGACTCCCCGCCGCCCCGGGCCCACCCGCAA GCATTACCAGCCCTATGCCCCACCACGCGACTTCGCAGCCTATCGCTCCAGAGTGAAGTTCAGCAGGA GCGCAGACGCCCCCGCGTACCAGCAGGGCCAGAACCAGCTCTATAACGAGCTCAATCTAGGACGAAGA GAGGAGTACGATGTTTTGGACAAGAGACGTGGCCGGGACCCTGAGATGGGGGGAAAGCCGAGAAGGAA GAACCCTCAGGAAGGCCTGTTCAATGAACTGCAGAAAGATAAGATGGCGGAGGCCTTCAGTGAGATTG GGATGAAAGGCGAGCGCCGGAGGGGCAAGGGGCACGATGGCCTTTTCCAGGGTCTCAGTACAGCCACC AAGGACACCTTCGACGCCCTTCACATGCAGGCCCTGCCCCCTCGC [SEQ ID NO: 36] In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain, ii) a transmembrane domain, iii) a hinge / spacer region, iv) an intracellular signaling domain comprising a) a native CD3ζ polypeptide, and b) a co- stimulatory signaling region comprising a 4-1BB polypeptide (e.g., a human 4-1BB polypeptide, e.g., an intracellular domain of 4-1BB (e.g., human 4-1BB) of a portion thereof). In certain embodiments, the intracellular signaling domain comprises a native CD3ζ polypeptide comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 16, and a co-stimulatory signaling region comprising a 4-1BB polypeptide that comprises or consists of 214 to 255 of SEQ ID NO: 34. In certain embodiments, the CAR is designated as “BBz”. 2.1.4. Exemplary Chimeric Antigen Receptors In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain targeting a B cell antigen, ii) a transmembrane domain, iii) a hinge / spacer region, and iv) an intracellular signaling domain. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a human scFv binding to the B cell antigen. In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain targeting CD19, ii) a transmembrane domain, iii) a hinge / spacer region, and iv) an intracellular signaling domain. In certain embodiments, the ACTIVE 511192992.1 37 072734.1806 PATENT extracellular antigen-binding domain of the CAR comprises a human scFv binding to CD19 (i.e., an scFv disclosed in International Patent Publication No. WO2021217130). In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain targeting CD19, ii) a transmembrane domain, iii) a hinge / spacer region, and iv) an intracellular signaling domain. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 70, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 71, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 72; and a VL comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 73, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 74, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 75. In certain embodiments, the transmembrane domain comprises a CD28 polypeptide comprising or consisting of amino acids 153 to 179 of SEQ ID NO: 15. In certain embodiments, the hinge / spacer region comprises a CD28 polypeptide comprising or consisting of amino acids 114 to 152 of SEQ ID NO: 15. In certain embodiments, the intracellular signaling domain comprises a modified CD3ζ polypeptide comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 30, and a co-stimulatory signaling region comprising a CD28 polypeptide that comprises or consists of 180 to 220 of SEQ ID NO: 15. In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain targeting FcRL5, ii) a transmembrane domain, iii) a hinge / spacer region, and iv) an intracellular signaling domain. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a VH comprising a CDR1 comprising amino acids having the sequence set forth in SEQ ID NO: 81, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 82, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 83; and a VL comprising a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 84, a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 85, and a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 86. In certain embodiments, the transmembrane domain comprises a CD28 polypeptide comprising or consisting of amino acids 153 to 179 of SEQ ID NO: 15. In certain embodiments, the hinge / spacer region comprises a CD28 polypeptide comprising or consisting of amino acids 114 to 152 of SEQ ID NO: 15. In certain embodiments, the intracellular signaling domain comprises a modified CD3ζ polypeptide comprising or consisting of the amino acid sequence set forth in SEQ ID NO: 30, and a co-stimulatory signaling region comprising a CD28 polypeptide that comprises or consists of 180 to 220 of SEQ ID NO: 15. ACTIVE 511192992.1 38 072734.1806 PATENT In certain embodiments, the antigen-recognizing receptor is a CAR that comprises i) an extracellular antigen-binding domain targeting BCMA, ii) a transmembrane domain, iii) a hinge / spacer region, and iv) an intracellular signaling domain. In certain embodiments, the extracellular antigen-binding domain of the CAR comprises a human scFv binding to BCMA (i.e., an scFv disclosed in International Patent Publication No. WO2016090320). 2.1.5. Delivery of the Chimeric Antigen Receptor In certain embodiments, the antigen-recognizing receptor (e.g., CAR) is delivered to the cell by a viral method. In certain embodiments, the viral method comprises a viral vector. In certain embodiments, the viral vector is a retroviral vector (e.g., a gammaretroviral vector or a lentiviral vector). Other viral vectors include adenoviral vectors, adeno-associated viral vectors, vaccinia viruses, bovine papilloma viruses, and herpes viruses (e.g., such as Epstein- Barr Virus). In certain embodiments, the antigen-recognizing receptor (e.g., CAR) is delivered to the cell by a non-viral method. Non-limiting examples of non-viral methods encompassed by the presently disclosed subject matter include plasmid, mini-plasmid, nanoplasmids, dsDNA, and ssRNA. Any targeted genome editing methods can also be used to deliver the antigen- recognizing receptor to the cell. In certain embodiments, the antigen-recognizing receptor (e.g., CAR) is delivered to the cell by a method comprising homologous recombination, a Zinc finger nuclease, a meganuclease, a Transcription activator-like effector nuclease (TALEN), a Clustered regularly-interspaced short palindromic repeats (CRISPR) system, or a combination thereof. In certain embodiments, a CRISPR system is used to deliver the antigen-recognizing receptor to the cell. In certain embodiments, the cell is a T cell, and the antigen-recognizing receptor is integrated at a locus within the genome of the T cell. Non-limiting examples of loci include a TRAC locus, a TRBC locus, a TRDC locus, and a TRGC locus. In certain embodiments, the locus is a TRAC locus or a TRBC locus. In certain embodiments, the cell is a T cell, and the antigen-recognizing receptor is integrated at a TRAC locus. Methods of targeting a CAR to a site within the genome of T cell are disclosed in WO2017180989 and Eyquem et al., Nature. (2017 Mar 2); 543(7643): 113–117, both of which are incorporated by reference in their entireties. In certain embodiments, the cell is a T cell, the antigen-recognizing receptor is a CAR, and the antigen-recognizing receptor is integrated at a TRAC locus. In certain ACTIVE 511192992.1 39 072734.1806 PATENT embodiments, the cell further comprises a gene disruption of a TRBC locus. In certain embodiments, the gene disruption of a TRBC locus results in knockout of TRBC locus. 2.2. TCR-Like Fusion Molecules In certain embodiments, the antigen-recognizing receptor is a TCR-like fusion molecule. Non-limiting examples of TCR fusion molecules include HLA-Independent TCR- based Chimeric Antigen Receptor (also known as “HIT”, e.g., those disclosed in International Patent Application No. PCT / US19 / 017525, which is incorporated by reference in its entirety), and T cell receptor fusion constructs (TRuCs) (e.g., those disclosed in Baeuerle et al., “Synthetic TRuC receptors engaging the complete T cell receptor for potent anti-tumor response,” Nature Communications volume 10, Article number: 2087 (2019), which is incorporated by reference in its entirety). In certain embodiments, the TCR-like fusion molecule is a recombinant T cell receptor (TCR). In certain embodiments, the recombinant TCR comprises at least one antigen-binding chain. In certain embodiments, the antigen-binding domain of the recombinant TCR comprises a ligand for a cell-surface receptor, a receptor for a cell surface ligand, an antigen binding portion of an antibody or a fragment thereof, or an antigen binding portion of a TCR. In certain embodiments, the recombinant TCR comprises two antigen binding chains, i.e., a first antigen binding chain and a second antigen binding chain. In certain embodiments, the first and second antigen-binding chains each comprises a constant domain. In certain embodiments, the recombinant TCR binds to an antigen (e.g., a first antigen or a second antigen) in an HLA- independent manner. Thus, in certain embodiments, the recombinant TCR is an HLA- independent (or non-HLA restricted) TCR (referred to as “HIT”). In certain embodiments, the first antigen-binding chain comprises an antigen-binding fragment of a heavy chain variable region (VH) of an antibody. In certain embodiments, the second antigen-binding chain comprises an antigen-binding fragment of a light chain variable region (VL) of an antibody. In certain embodiments, the first antigen-binding chain comprises an antigen-binding fragment of a VHof an antibody, and the second antigen-binding chain comprises an antigen-binding fragment of a VL of the antibody. In certain embodiments, the constant domain comprises a TCR constant region selected from the group consisting of a native or modified TRAC polypeptide, a native or modified TRBC polypeptide, a native or modified TRDC polypeptide, a native or modified TRGC polypeptide and any variants or functional fragments thereof. In certain embodiments, the constant domain comprises a native or modified TRAC polypeptide. In certain embodiments, ACTIVE 511192992.1 40 072734.1806 PATENT the constant domain comprises a native or modified TRBC polypeptide. In certain embodiments, the first antigen-binding chain comprises a TRAC polypeptide, and the second antigen-binding chain comprises a TRBC polypeptide. In certain embodiments, the first antigen-binding chain comprises a TRBC polypeptide, and the second antigen-binding chain comprises a TRAC polypeptide. In certain embodiments, the first antigen-binding chain comprises a VH of an antibody and a TRAC polypeptide, and the second antigen-binding chain comprises a VLof an antibody and a TRBC polypeptide. In certain embodiments, the first antigen-binding chain comprises a VH of an antibody and a TRBC polypeptide, and the second antigen-binding chain comprises a VLof an antibody and a TRAC polypeptide. In certain embodiments, at least one of the TRAC polypeptide and the TRBC polypeptide is endogenous. In certain embodiments, the TRAC polypeptide is endogenous. In certain embodiments, the TRBC polypeptide is endogenous. In certain embodiments, both the TRAC polypeptide and the TRBC polypeptide are endogenous. In certain embodiments, the antigen binding chain is capable of associating with a CD3ζ polypeptide. In certain embodiments, the antigen binding chain, upon binding to an antigen, is capable of activating the CD3ζ polypeptide associated to the antigen binding chain. In certain embodiments, the activation of the CD3ζ polypeptide is capable of activating an immunoresponsive cell. In certain embodiments, the TCR-like fusion molecule is capable of integrating with a CD3 complex and providing HLA-independent antigen recognition. In certain embodiments, the TCR-like fusion molecule replaces an endogenous TCR in a CD3 / TCR complex. In certain embodiments, the first and second antigen binding chains bind to an antigen with a dissociation constant (KD) of about 2 × 10-7M or less. In certain embodiments, the first and second antigen binding chains bind to an antigen with a high binding affinity. In certain embodiments, the KDis about 2 × 10-7M or less, about 1 × 10-7M or less, about 9 × 10-8M or less, about 1 × 10-8M or less, about 9 × 10-9M or less, about 5 × 10-9M or less, about 4 × 10-9M or less, about 3 × 10-9or less, about 2 ×10-9M or less, or about 1 × 10-9M or less. In certain embodiments, the KDis about 1 × 10-8M or less. In certain embodiments, the KDis about 3 × 10-9M or less. In certain embodiments, the KDis about 5 × 10-9M or less. In certain embodiments, the KD is from about 1 × 10-9M to about 1 × 10-8M. In certain embodiments, the KD is from about 1.5 × 10-9M to about 1 × 10-8M. In certain embodiments, the KD is from about 5 × 10-9M to about 1 × 10-8M. ACTIVE 511192992.1 41 072734.1806 PATENT In certain embodiments, the constant domain comprises a TCR constant region, e.g., T cell receptor alpha constant region (TRAC), T cell receptor beta constant region (TRBC, e.g., TRBC1 or TRBC2), T cell receptor gamma constant region (TRGC, e.g., TRGC1 or TRGC2), T cell receptor delta constant region (TRDC) or any variants or functional fragments thereof. In certain embodiments, the first antigen binding chain or the second antigen binding chain comprises a constant domain that comprises a native or modified TRAC polypeptide. In certain embodiments, the TRAC polypeptide comprises an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 37 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRAC polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 37. SEQ ID NO: 37 is provided below. IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWSNKS DFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLMTLR LWSS [SEQ ID NO: 37] An exemplary nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 37 is set forth in SEQ ID NO: 38, which is provided below. ATCCAGAACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCT ATTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCACAGACA AAACTGTGCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAATCT GACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCAGA AAGTTCCTGTGATGTCAAGCTGGTCGAGAAAAGCTTTGAAACAGATACGAACCTAAACTTTCAAAACC TGTCAGTGATTGGGTTCCGAATCCTCCTCCTGAAAGTGGCCGGGTTTAATCTGCTCATGACGCTGCGG CTGTGGTCCAGC [SEQ ID NO: 38] In certain embodiments, the TRAC polypeptide comprises an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 39 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRAC polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 39. SEQ ID NO: 39 is provided below. ACTIVE 511192992.1 42 072734.1806 PATENT IPNIQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSNSAVAWS NKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFRILLLKVAGFNLLM TLRLWSS [SEQ ID NO: 39] An exemplary nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 39 is set forth in SEQ ID NO: 40, which is provided below. ATTCCCAATATCCAGAACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTC TGTCTGCCTATTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATA TCACAGACAAAACTGTGCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGC AACAAATCTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGACACCTTCTTCCC CAGCCCAGAAAGTTCCTGTGATGTCAAGCTGGTCGAGAAAAGCTTTGAAACAGATACGAACCTAAACT TTCAAAACCTGTCAGTGATTGGGTTCCGAATCCTCCTCCTGAAAGTGGCCGGGTTTAATCTGCTCATG ACGCTGCGGCTGTGGTCCAGC [SEQ ID NO: 40] In certain embodiments, the TRAC polypeptide comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence encoded by a transcript expressed by the gene of NCBI Genbank ID: 28755, NG_001332.3, range 925603 to 930229 (SEQ ID NO: 41) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRAC polypeptide comprises or consists of the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 41. SEQ ID NO: 41 is provided below. ATATCCAGAACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGC CTATTCACCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCACAGA CAAAACTGTGCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAAT CTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCA GGTAAGGGCAGCTTTGGTGCCTTCGCAGGCTGTTTCCTTGCTTCAGGAATGGCCAGGTTCTGCCCAGA GCTCTGGTCAATGATGTCTAAAACTCCTCTGATTGGTGGTCTCGGCCTTATCCATTGCCACCAAAACC CTCTTTTTACTAAGAAACAGTGAGCCTTGTTCTGGCAGTCCAGAGAATGACACGGGAAAAAAGCAGAT GAAGAGAAGGTGGCAGGAGAGGGCACGTGGCCCAGCCTCAGTCTCTCCAACTGAGTTCCTGCCTGCCT GCCTTTGCTCAGACTGTTTGCCCCTTACTGCTCTTCTAGGCCTCATTCTAAGCCCCTTCTCCAAGTTG CCTCTCCTTATTTCTCCCTGTCTGCCAAAAAATCTTTCCCAGCTCACTAAGTCAGTCTCACGCAGTCA CTCATTAACCCACCAATCACTGATTGTGCCGGCACATGAATGCACCAGGTGTTGAAGTGGAGGAATTA AAAAGTCAGATGAGGGGTGTGCCCAGAGGAAGCACCATTCTAGTTGGGGGAGCCCATCTGTCAGCTGG GAAAAGTCCAAATAACTTCAGATTGGAATGTGTTTTAACTCAGGGTTGAGAAAACAGCTACCTTCAGG ACAAAAGTCAGGGAAGGGCTCTCTGAAGAAATGCTACTTGAAGATACCAGCCCTACCAAGGGCAGGGA ACTIVE 511192992.1 43 072734.1806 PATENT GAGGACCCTATAGAGGCCTGGGACAGGAGCTCAATGAGAAAGGAGAAGAGCAGCAGGCATGAGTTGAA TGAAGGAGGCAGGGCCGGGTCACAGGGCCTTCTAGGCCATGAGAGGGTAGACAGTATTCTAAGGACGC CAGAAAGCTGTTGATCGGCTTCAAGCAGGGGAGGGACACCTAATTTGCTTTTCTTTTTTTTTTTTTTT TTTTTTTTTTTTTTTGAGATGGAGTTTTGCTCTTGTTGCCCAGGCTGGAGTGCAATGGTGCATCTTGG CTCACTGCAACCTCCGCCTCCCAGGTTCAAGTGATTCTCCTGCCTCAGCCTCCCGAGTAGCTGAGATT ACAGGCACCCGCCACCATGCCTGGCTAATTTTTTGTATTTTTAGTAGAGACAGGGTTTCACTATGTTG GCCAGGCTGGTCTCGAACTCCTGACCTCAGGTGATCCACCCGCTTCAGCCTCCCAAAGTGCTGGGATT ACAGGCGTGAGCCACCACACCCGGCCTGCTTTTCTTAAAGATCAATCTGAGTGCTGTACGGAGAGTGG GTTGTAAGCCAAGAGTAGAAGCAGAAAGGGAGCAGTTGCAGCAGAGAGATGATGGAGGCCTGGGCAGG GTGGTGGCAGGGAGGTAACCAACACCATTCAGGTTTCAAAGGTAGAACCATGCAGGGATGAGAAAGCA AAGAGGGGATCAAGGAAGGCAGCTGGATTTTGGCCTGAGCAGCTGAGTCAATGATAGTGCCGTTTACT AAGAAGAAACCAAGGAAAAAATTTGGGGTGCAGGGATCAAAACTTTTTGGAACATATGAAAGTACGTG TTTATACTCTTTATGGCCCTTGTCACTATGTATGCCTCGCTGCCTCCATTGGACTCTAGAATGAAGCC AGGCAAGAGCAGGGTCTATGTGTGATGGCACATGTGGCCAGGGTCATGCAACATGTACTTTGTACAAA CAGTGTATATTGAGTAAATAGAAATGGTGTCCAGGAGCCGAGGTATCGGTCCTGCCAGGGCCAGGGGC TCTCCCTAGCAGGTGCTCATATGCTGTAAGTTCCCTCCAGATCTCTCCACAAGGAGGCATGGAAAGGC TGTAGTTGTTCACCTGCCCAAGAACTAGGAGGTCTGGGGTGGGAGAGTCAGCCTGCTCTGGATGCTGA AAGAATGTCTGTTTTTCCTTTTAGAAAGTTCCTGTGATGTCAAGCTGGTCGAGAAAAGCTTTGAAACA GGTAAGACAGGGGTCTAGCCTGGGTTTGCACAGGATTGCGGAAGTGATGAACCCGCAATAACCCTGCC TGGATGAGGGAGTGGGAAGAAATTAGTAGATGTGGGAATGAATGATGAGGAATGGAAACAGCGGTTCA AGACCTGCCCAGAGCTGGGTGGGGTCTCTCCTGAATCCCTCTCACCATCTCTGACTTTCCATTCTAAG CACTTTGAGGATGAGTTTCTAGCTTCAATAGACCAAGGACTCTCTCCTAGGCCTCTGTATTCCTTTCA ACAGCTCCACTGTCAAGAGAGCCAGAGAGAGCTTCTGGGTGGCCCAGCTGTGAAATTTCTGAGTCCCT TAGGGATAGCCCTAAACGAACCAGATCATCCTGAGGACAGCCAAGAGGTTTTGCCTTCTTTCAAGACA AGCAACAGTACTCACATAGGCTGTGGGCAATGGTCCTGTCTCTCAAGAATCCCCTGCCACTCCTCACA CCCACCCTGGGCCCATATTCATTTCCATTTGAGTTGTTCTTATTGAGTCATCCTTCCTGTGGTAGCGG AACTCACTAAGGGGCCCATCTGGACCCGAGGTATTGTGATGATAAATTCTGAGCACCTACCCCATCCC CAGAAGGGCTCAGAAATAAAATAAGAGCCAAGTCTAGTCGGTGTTTCCTGTCTTGAAACACAATACTG TTGGCCCTGGAAGAATGCACAGAATCTGTTTGTAAGGGGATATGCACAGAAGCTGCAAGGGACAGGAG GTGCAGGAGCTGCAGGCCTCCCCCACCCAGCCTGCTCTGCCTTGGGGAAAACCGTGGGTGTGTCCTGC AGGCCATGCAGGCCTGGGACATGCAAGCCCATAACCGCTGTGGCCTCTTGGTTTTACAGATACGAACC TAAACTTTCAAAACCTGTCAGTGATTGGGTTCCGAATCCTCCTCCTGAAAGTGGCCGGGTTTAATCTG CTCATGACGCTGCGGCTGTGGTCCAGCTGAGGTGAGGGGCCTTGAAGCTGGGAGTGGGGTTTAGGGAC GCGGGTCTCTGGGTGCATCCTAAGCTCTGAGAGCAAACCTCCCTGCAGGGTCTTGCTTTTAAGTCCAA AGCCTGAGCCCACCAAACTCTCCTACTTCTTCCTGTTACAAATTCCTCTTGTGCAATAATAATGGCCT GAAACGCTGTAAAATATCCTCATTTCAGCCGCCTCAGTTGCACTTCTCCCCTATGAGGTAGGAAGAAC AGTTGTTTAGAAACGAAGAAACTGAGGCCCCACAGCTAATGAGTGGAGGAAGAGAGACACTTGTGTAC ACTIVE 511192992.1 44 072734.1806 PATENT ACCACATGCCTTGTGTTGTACTTCTCTCACCGTGTAACCTCCTCATGTCCTCTCTCCCCAGTACGGCT CTCTTAGCTCAGTAGAAAGAAGACATTACACTCATATTACACCCCAATCCTGGCTAGAGTCTCCGCAC CCTCCTCCCCCAGGGTCCCCAGTCGTCTTGCTGACAACTGCATCCTGTTCCATCACCATCAAAAAAAA ACTCCAGGCTGGGTGCGGGGGCTCACACCTGTAATCCCAGCACTTTGGGAGGCAGAGGCAGGAGGAGC ACAGGAGCTGGAGACCAGCCTGGGCAACACAGGGAGACCCCGCCTCTACAAAAAGTGAAAAAATTAAC CAGGTGTGGTGCTGCACACCTGTAGTCCCAGCTACTTAAGAGGCTGAGATGGGAGGATCGCTTGAGCC CTGGAATGTTGAGGCTACAATGAGCTGTGATTGCGTCACTGCACTCCAGCCTGGAAGACAAAGCAAGA TCCTGTCTCAAATAATAAAAAAAATAAGAACTCCAGGGTACATTTGCTCCTAGAACTCTACCACATAG CCCCAAACAGAGCCATCACCATCACATCCCTAACAGTCCTGGGTCTTCCTCAGTGTCCAGCCTGACTT CTGTTCTTCCTCATTCCAGATCTGCAAGATTGTAAGACAGCCTGTGCTCCCTCGCTCCTTCCTCTGCA TTGCCCCTCTTCTCCCTCTCCAAACAGAGGGAACTCTCCTACCCCCAAGGAGGTGAAAGCTGCTACCA CCTCTGTGCCCCCCCGGCAATGCCACCAACTGGATCCTACCCGAATTTATGATTAAGATTGCTGAAGA GCTGCCAAACACTGCTGCCACCCCCTCTGTTCCCTTATTGCTGCTTGTCACTGCCTGACATTCACGGC AGAGGCAAGGCTGCTGCAGCCTCCCCTGGCTGTGCACATTCCCTCCTGCTCCCCAGAGACTGCCTCCG CCATCCCACAGATGATGGATCTTCAGTGGGTTCTCTTGGGCTCTAGGTCCTGCAGAATGTTGTGAGGG GTTTATTTTTTTTTAATAGTGTTCATAAAGAAATACATAGTATTCTTCTTCTCAAGACGTGGGGGGAA ATTATCTCATTATCGAGGCCCTGCTATGCTGTGTATCTGGGCGTGTTGTATGTCCTGCTGCCGATGCC TTC [SEQ ID NO: 41] In certain embodiments, the first antigen binding chain or the second antigen binding chain comprises a constant domain comprising a native or modified TRBC polypeptide. In certain embodiments, the TRBC polypeptide is a TRBC2 polypeptide. In certain embodiments, the TRBC2 polypeptide comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 42 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRBC2 polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 42. SEQ ID NO: 42 is provided below. DLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSES YQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDSRG [SEQ ID NO: 42] An exemplary nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 42 is set forth in SEQ ID NO: 43, which is provided below. GATCTGAAAAACGTGTTCCCTCCTGAAGTGGCTGTCTTTGAACCATCCGAGGCCGAGATTTCCCATAC CCAGAAAGCAACTCTGGTCTGTCTGGCCACTGGATTCTACCCCGATCACGTGGAACTGTCTTGGTGGG ACTIVE 511192992.1 45 072734.1806 PATENT TGAACGGCAAGGAAGTCCATTCCGGAGTCTCTACCGACCCTCAGCCCCTCAAGGAGCAGCCTGCTCTC AACGATTCTCGGTACTGCCTGTCATCTCGACTGAGAGTGTCTGCCACCTTCTGGCAGAACCCTAGAAA CCACTTTCGGTGTCAGGTCCAGTTTTACGGCCTGAGCGAGAACGATGAGTGGACACAGGATAGAGCCA AACCTGTGACACAGATTGTGAGCGCCGAGGCTTGGGGACGAGCCGATTGTGGCTTCACATCCGAGTCT TACCAGCAGGGAGTGCTGTCTGCTACAATCCTCTACGAAATTCTCCTGGGGAAGGCCACCCTGTACGC TGTCCTCGTGTCTGCTCTGGTGCTCATGGCTATGGTCAAACGAAAGGACTCTAGAGGC [SEQ ID NO: 43] In certain embodiments, the TRBC polypeptide is a TRBC2 polypeptide. In certain embodiments, the TRBC2 polypeptide comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 44 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRBC2 polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 44. SEQ ID NO: 44 is provided below. LEDLKNVFPPEVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDPQPLKEQP ALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTS ESYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDSRG [SEQ ID NO: 44] An exemplary nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 44 is set forth in SEQ ID NO: 45, which is provided below. CTGGAGGATCTGAAAAACGTGTTCCCTCCTGAAGTGGCTGTCTTTGAACCATCCGAGGCCGAGATTTC CCATACCCAGAAAGCAACTCTGGTCTGTCTGGCCACTGGATTCTACCCCGATCACGTGGAACTGTCTT GGTGGGTGAACGGCAAGGAAGTCCATTCCGGAGTCTCTACCGACCCTCAGCCCCTCAAGGAGCAGCCT GCTCTCAACGATTCTCGGTACTGCCTGTCATCTCGACTGAGAGTGTCTGCCACCTTCTGGCAGAACCC TAGAAACCACTTTCGGTGTCAGGTCCAGTTTTACGGCCTGAGCGAGAACGATGAGTGGACACAGGATA GAGCCAAACCTGTGACACAGATTGTGAGCGCCGAGGCTTGGGGACGAGCCGATTGTGGCTTCACATCC GAGTCTTACCAGCAGGGAGTGCTGTCTGCTACAATCCTCTACGAAATTCTCCTGGGGAAGGCCACCCT GTACGCTGTCCTCGTGTCTGCTCTGGTGCTCATGGCTATGGTCAAACGAAAGGACTCTAGAGGC [SEQ ID NO: 45] In certain embodiments, the TRBC polypeptide is a TRBC1 polypeptide. In certain embodiments, the TRBC1 polypeptide comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 46 or a fragment ACTIVE 511192992.1 46 072734.1806 PATENT thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRBC1 polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 46. SEQ ID NO: 46 is provided below. LNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPALN DSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVSY QQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF [SEQ ID NO: 46] In certain embodiments, the TRBC1 polypeptide comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 47 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRBC1 polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 47. SEQ ID NO: 47 is provided below. DLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPLKEQPAL NDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIVSAEAWGRADCGFTSVS YQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF [SEQ ID NO: 47] An exemplary nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 47 is set forth in SEQ ID NO: 48, which is provided below. GACCTGAACAAGGTGTTCCCACCCGAGGTCGCTGTGTTTGAGCCATCAGAAGCAGAGATCTCCCACAC CCAAAAGGCCACACTGGTGTGCCTGGCCACAGGCTTCTTCCCCGACCACGTGGAGCTGAGCTGGTGGG TGAATGGGAAGGAGGTGCACAGTGGGGTCAGCACAGACCCGCAGCCCCTCAAGGAGCAGCCCGCCCTC AATGACTCCAGATACTGCCTGAGCAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCCGCAA CCACTTCCGCTGTCAAGTCCAGTTCTACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGCCA AACCCGTCACCCAGATCGTCAGCGCCGAGGCCTGGGGTAGAGCAGACTGTGGCTTTACCTCGGTGTCC TACCAGCAAGGGGTCCTGTCTGCCACCATCCTCTATGAGATCCTGCTAGGGAAGGCCACCCTGTATGC TGTGCTGGTCAGCGCCCTTGTGTTGATGGCCATGGTCAAGAGAAAGGATTTC [SEQ ID NO: 48] In certain embodiments, the TRBC polypeptide comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or at least about 100% homologous or identical to the amino acid sequence encoded by a transcript expressed by a gene of NCBI Genbank ID: 28639, NG_001333.2, range 645749 to 647196 (TRBC1, SEQ ID NO: 49), NCBI Genbank ID: 28638, NG_001333.2 range 655095 to 656583 (TRBC2, SEQ ACTIVE 511192992.1 47 072734.1806 PATENT ID NO: 50) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRBC polypeptide comprises or consists of the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 49. In certain embodiments, the TRBC polypeptide comprises or consists of the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 50. SEQ ID NO: 49 and 50 are provided below. AGGACCTGAACAAGGTGTTCCCACCCGAGGTCGCTGTGTTTGAGCCATCAGAAGCAGAGATCTCCCAC ACCCAAAAGGCCACACTGGTGTGCCTGGCCACAGGCTTCTTCCCCGACCACGTGGAGCTGAGCTGGTG GGTGAATGGGAAGGAGGTGCACAGTGGGGTCAGCACAGACCCGCAGCCCCTCAAGGAGCAGCCCGCCC TCAATGACTCCAGATACTGCCTGAGCAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCCGC AACCACTTCCGCTGTCAAGTCCAGTTCTACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGC CAAACCCGTCACCCAGATCGTCAGCGCCGAGGCCTGGGGTAGAGCAGGTGAGTGGGGCCTGGGGAGAT GCCTGGAGGAGATTAGGTGAGACCAGCTACCAGGGAAAATGGAAAGATCCAGGTAGCAGACAAGACTA GATCCAAAAAGAAAGGAACCAGCGCACACCATGAAGGAGAATTGGGCACCTGTGGTTCATTCTTCTCC CAGATTCTCAGCCCAACAGAGCCAAGCAGCTGGGTCCCCTTTCTATGTGGCCTGTGTAACTCTCATCT GGGTGGTGCCCCCCATCCCCCTCAGTGCTGCCACATGCCATGGATTGCAAGGACAATGTGGCTGACAT CTGCATGGCAGAAGAAAGGAGGTGCTGGGCTGTCAGAGGAAGCTGGTCTGGGCCTGGGAGTCTGTGCC AACTGCAAATCTGACTTTACTTTTAATTGCCTATGAAAATAAGGTCTCTCATTTATTTTCCTCTCCCT GCTTTCTTTCAGACTGTGGCTTTACCTCGGGTAAGTAAGCCCTTCCTTTTCCTCTCCCTCTCTCATGG TTCTTGACCTAGAACCAAGGCATGAAGAACTCACAGACACTGGAGGGTGGAGGGTGGGAGAGACCAGA GCTACCTGTGCACAGGTACCCACCTGTCCTTCCTCCGTGCCAACAGTGTCCTACCAGCAAGGGGTCCT GTCTGCCACCATCCTCTATGAGATCCTGCTAGGGAAGGCCACCCTGTATGCTGTGCTGGTCAGCGCCC TTGTGTTGATGGCCATGGTAAGCAGGAGGGCAGGATGGGGCCAGCAGGCTGGAGGTGACACACTGACA CCAAGCACCCAGAAGTATAGAGTCCCTGCCAGGATTGGAGCTGGGCAGTAGGGAGGGAAGAGATTTCA TTCAGGTGCCTCAGAAGATAACTTGCACCTCTGTAGGATCACAGTGGAAGGGTCATGCTGGGAAGGAG AAGCTGGAGTCACCAGAAAACCCAATGGATGTTGTGATGAGCCTTACTATTTGTGTGGTCAATGGGCC CTACTACTTTCTCTCAATCCTCACAACTCCTGGCTCTTAATAACCCCCAAAACTTTCTCTTCTGCAGG TCAAGAGAAAGGATTTCTGA [SEQ ID NO: 49] AGGACCTGAAAAACGTGTTCCCACCCGAGGTCGCTGTGTTTGAGCCATCAGAAGCAGAGATCTCCCAC ACCCAAAAGGCCACACTGGTATGCCTGGCCACAGGCTTCTACCCCGACCACGTGGAGCTGAGCTGGTG GGTGAATGGGAAGGAGGTGCACAGTGGGGTCAGCACAGACCCGCAGCCCCTCAAGGAGCAGCCCGCCC TCAATGACTCCAGATACTGCCTGAGCAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCCGC AACCACTTCCGCTGTCAAGTCCAGTTCTACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGC CAAACCCGTCACCCAGATCGTCAGCGCCGAGGCCTGGGGTAGAGCAGGTGAGTGGGGCCTGGGGAGAT GCCTGGAGGAGATTAGGTGAGACCAGCTACCAGGGAAAATGGAAAGATCCAGGTAGCGGACAAGACTA GATCCAGAAGAAAGCCAGAGTGGACAAGGTGGGATGATCAAGGTTCACAGGGTCAGCAAAGCACGGTG ACTIVE 511192992.1 48 072734.1806 PATENT TGCACTTCCCCCACCAAGAAGCATAGAGGCTGAATGGAGCACCTCAAGCTCATTCTTCCTTCAGATCC TGACACCTTAGAGCTAAGCTTTCAAGTCTCCCTGAGGACCAGCCATACAGCTCAGCATCTGAGTGGTG TGCATCCCATTCTCTTCTGGGGTCCTGGTTTCCTAAGATCATAGTGACCACTTCGCTGGCACTGGAGC AGCATGAGGGAGACAGAACCAGGGCTATCAAAGGAGGCTGACTTTGTACTATCTGATATGCATGTGTT TGTGGCCTGTGAGTCTGTGATGTAAGGCTCAATGTCCTTACAAAGCAGCATTCTCTCATCCATTTTTC TTCCCCTGTTTTCTTTCAGACTGTGGCTTCACCTCCGGTAAGTGAGTCTCTCCTTTTTCTCTCTATCT TTCGCCGTCTCTGCTCTCGAACCAGGGCATGGAGAATCCACGGACACAGGGGCGTGAGGGAGGCCAGA GCCACCTGTGCACAGGTGCCTACATGCTCTGTTCTTGTCAACAGAGTCTTACCAGCAAGGGGTCCTGT CTGCCACCATCCTCTATGAGATCTTGCTAGGGAAGGCCACCTTGTATGCCGTGCTGGTCAGTGCCCTC GTGCTGATGGCCATGGTAAGGAGGAGGGTGGGATAGGGCAGATGATGGGGGCAGGGGATGGAACATCA CACATGGGCATAAAGGAATCTCAGAGCCAGAGCACAGCCTAATATATCCTATCACCTCAATGAAACCA TAATGAAGCCAGACTGGGGAGAAAATGCAGGGAATATCACAGAATGCATCATGGGAGGATGGAGACAA CCAGCGAGCCCTACTCAAATTAGGCCTCAGAGCCCGCCTCCCCTGCCCTACTCCTGCTGTGCCATAGC CCCTGAAACCCTGAAAATGTTCTCTCTTCCACAGGTCAAGAGAAAGGATTCCAGAGGCTAG [SEQ ID NO: 50] In certain embodiments, the first antigen binding chain or the second antigen binding chain comprises a constant domain comprising a native or modified TRGC polypeptide. In certain embodiments, the TRGC polypeptide is a native or modified TRGC1 polypeptide. In certain embodiments, the TRGC1 polypeptide comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 51, which is provided below. In certain embodiments, the TRGC1 polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 51. DKQLDADVSPKPTIFLPSIAETKLQKAGTYLCLLEKFFPDVIKIHWQEKKSNTILGSQEGNTMKTNDT YMKFSWLTVPEKSLDKEHRCIVRHENNKNGVDQEIIFPPIKTDVITMDPKDNCSKDANDTLLLQLTNT SAYYMYLLLLLKSVVYFAIITCCLLRRTAFCCNGEKS [SEQ ID NO: 51] In certain embodiments, the TRGC polypeptide is a native or modified TRGC2 polypeptide. In certain embodiments, the TRGC2 polypeptide comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 52, which is provided below. In certain embodiments, the TRGC2 polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 52. DKQLDADVSPKPTIFLPSIAETKLQKAGTYLCLLEKFFPDIIKIHWQEKKSNTILGSQEGNTMKTNDT YMKFSWLTVPEESLDKEHRCIVRHENNKNGIDQEIIFPPIKTDVTTVDPKYNYSKDANDVITMDPKDN WSKDANDTLLLQLTNTSAYYTYLLLLLKSVVYFAIITCCLLRRTAFCCNGEKS [SEQ ID NO: 52] ACTIVE 511192992.1 49 072734.1806 PATENT In certain embodiments, the TRGC polypeptide comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or 100% homologous or identical to the amino acid sequence encoded by a transcript expressed by a gene of NCBI Genbank ID: 6966, NG_001336.2, range 108270 to 113860 (TRGC1, SEQ ID NO: 53), NCBI Genbank ID: 6967, NG_001336.2, range 124376 to 133924 (TRGC2, SEQ ID NO: 54) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the TRGC polypeptide comprises or consists of the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 53. In certain embodiments, the TRGC polypeptide comprises or consists of the amino acid sequence encoded by the nucleotide sequence of SEQ ID NO: 54. SEQ ID NO: 53 and 54 are provided below. ATAAACAACTTGATGCAGATGTTTCCCCCAAGCCCACTATTTTTCTTCCTTCAATTGCTGAAACAAAG CTCCAGAAGGCTGGAACATACCTTTGTCTTCTTGAGAAATTTTTCCCTGATGTTATTAAGATACATTG GCAAGAAAAGAAGAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCATGAAGACTAACGACACAT ACATGAAATTTAGCTGGTTAACGGTGCCAGAAAAGTCACTGGACAAAGAACACAGATGTATCGTCAGA CATGAGAATAATAAAAACGGAGTTGATCAAGAAATTATCTTTCCTCCAATAAAGACAGGTATGTGTTT ACGCATATCATCTGTCAGAACACTTCTTTGAAAGTGAATGCTGCATTTTTTCCTTTCAGTATTAATGA AAAACAAACATAAATCTTTCTTAAATATTGTTACATTTAATGGTAGCATAAATGCCCTGCTACTTTTC TATAGAATTAAAATGGTATAGGTTTTGGAGAAAACAAAATTGAAAAAGTTACTGAAGGTTTGTCAGCC TCAGCTCCATTATCCAAAATAAGAAAGTCACGTGCTGGTTTTTAGGGTTGTTAGATGGATTAAAGAAA CAACATACACAGAAGCATCTAGCAACGTGACACGTGGTAAACGCTCAAAAAGTGTTCTCCCTTCTTTT GATGACTTTACTTGATCAGGAAATAACATATATATGTCTTTCAGGAATGTTCTGCCCAAGCAGGAGAG TCACTCACCTCAATCTTGCTACCCACAAAGTTTAACCTAAAAACAACGGGTTCATTGTTGACAAAATG ATGTTTATCTGTTGTTGACAGAATGATGTTTATCTAAAAACAGTTCCAATTTTCTATTTCCTTTGCTG AGACACAAAGGGGAGGCAAATGTGCAAAGCTTGAGGGTAGTCTTACCACTGTGCTTAAGTGTTCTGAT TTTTCTAGTGATCAGGGCAAAATAAAAAGTATAGTAAGTTCCAAGGCAGTGAATATTATACAGGAGAG AAGTTACAGTTTTATAATGTGTTTTCCTTTACACTAAATTCTAAAAGTAAAAAGTCTTTTTTTTTTTT TGACAGAGTTTCACTCTTGTTGCCCAAGCAGGTGTGCTATGGTATGATCTCAGCTCACTGCAACCTCC ACCTCCCGGGTTCAAGTGATTCTCTTACTTCAGCCTCCCGACAGGCTGGGATTGCAGGCGCCTGCCAC CACACCTGGCTAATTTTTGTGTTTTTAGTAGAGATGGGGTTTCACCATGTTGGCCAGGCTGGTCTCAA ATTCCTGACCTCAAGTGATCCATCCACCTCGGCCTCCAAGTGCTGGGATTATGGGCGTCAGCCACTGT GCCCAGCCTAAAAGTAAAATGTCTTTCATGAGCTTCCCAAGGCAGCTACGTTAAGGAGGACACTTCTC TTAATGTCATTCTACAGTAGATTTCTAATGCTCTTTCTTGGAAGTTTGTTTTTCTGAGAAAAGCTAAA AATATAACATGGAAGTGATCATATTATATAATCAATGAAGTGCTTTTCAAGGAGATAAAACTAATCTG GTCCACACTTGCAACCAACCTTGATTGAGAGAGAGAGAGAACTCAGGATACACTTGAAGATTTTATTA TGGGGAACAGTTACTTTATTCTTTTTACCTCAATCAATGCATGGAAATAAGTGATAGTCATTTTCATT ACTIVE 511192992.1 50 072734.1806 PATENT TATCTTTTAATAAATGAAGTCACCATGAGGAAAATAAAAAGACATTGAAAACCCATTAAAGTCAGCCC TTAAAGATATTTGGACATGCAGACTTGATAACTAACGTTTGCATTCTTGAGACTTACCCAAAACCCAT ACCTCAAGTCCAAGTTTTTAGAATTCATGAAATAAAGATCTCAGTGAGTGCATAAAATTGCGCACCAG AATCATATCCGTATAGACAAGAACACATCTACTAGAAAAATAATAAACCAACACACCAATGCAACTGT GTTTTCTTCTGTTTTAAAGTATGTTGTCTTTGTATGCATGTTTGCTTCTTCCTTTTTTTTTTTAACAT CACAGATAAATTCAACTCTCACCTCAGGTTTTATTGAGAGAACTGTCAATGTGACTTGGCCTCTGTCT TTCTAGTCCCAGAAAGAATTGCACTGAAATCTGAGCTCCTGTAATAAAAACAACCATTTGCTGAGAGT AATTAACATACTGAAAGAGATTTTCTTAGAGTACACAATGGTGACATTATATTGCCTCTTTATAAATA ACTTTCTATCTATTTCTGTGGATTATTCCTACAAAGTACTTTTCATATGTCCAATTTCTTTTCTTCCC CTACAACTACTGTCTGAATACTGGCTCTGCTATTTGCTGATATGATTCTCGGCAAGTTGCCTGCACTT TTTAAACTTTATTTCCTCATTCAGAACATGGGGCCATACATAATACAACTCACTTCAGTGTTATTGGG GAATTAAACAAAAAATGCATGGGAAGCATTTAACATAGTGCCTGACACAATAATGAGTACTCAGTAGA TGTTAGCTTTTATTAATATTGTTGTTGTTATGTCCAGAAACACTATACCTCCAGAAAATCATGGGTAC TTGCTGGGGACATTGGGGATATGCATGATTTGGAAAAGAATGACTGCTTTTTTTGCTTAGATGAGAAA TTTTTCTAAGCCAGACTCCTTCAAATATGTAAGATTCTGTTGTGGATTCAAGGACTGAAAGAATTCTT GGCCGAGTGTGGTGGCTTATCCCTGTAATCCCAGCATTTTGTGAGGACAAGGCAGGAAGATTGCTTGA GTCCAGGAGTTTGAAACCAGCCTGCGCAACATGGCGAAACCCTGTCTCTACAAAAAATACAAACATTA GCTCGGAGTGAGTGCTGACATGTGCCTGTACTCCCAGCTACTCAGAAGGCTGAGATGGGAGGATCTCA TGAGCCTGGGGAGTTTGAGGCTTCAGTGAGCCGTGATGACACCGTACTATACTCCACTCCAGCCTGGG TGACAGTGAGACCCTGCCTCAAAAAACAAACAAACAAACAAACAAAACAAAATTAATCTTTTTGCTGA TGTCATGTCAGCAGTGTGTGTTGAAGGCTGTAAAGCAGCCATTTGTTCAGTTTATTTTTCCATTGAAC AAGTATTTATCAAAAACATACTTTGTGGCAGTCACTATGCTAGGAGCTATGAATACAGAAGGAAAAGT AAATGCTCTTGGATACTACACTCCAGTTGTGATAAAAAAGAAAAAATGTATTCTTCACCAACTTCAAC ATCTTGATGTGCAAAAACATAATACATGAATTAGATCTACCTAATTACACAGAATTAGACCAATTGTT TCTGGAATTGTGGGCTCATATTTTTAATAACTGTCCTCCTGCCTCTCTGTCGACAGGTTTTATAAATA TTCATTTAATTACACACACACACACGAACAATTGACTAGTACTTGCTCTCATTCTTCTAGATGTCATC ACAATGGATCCCAAAGACAATTGTTCAAAAGATGCAAATGGTAAGCTTTTGTGTTTTTCCCTTCCTCC TGATCATTTTGTTTTGAACTTCTCTGGCTTGAAAAATCAGGGAATGGATTTTGCTAGGTTGGATGCTG CAGAATGGACCTAGTGATATTTTAAATTAGTCCCTCATTTTCTAGGAGTTGTATTAACAAACCTAACT ACTGCTTTGGGGTATGAGATGACTGTAAATTAGAGAGGGTACAGTGGTATAGTGATATGCTTTTAATT ATTTCAAAAAAAAGATTTTATTCATTCATGTGTCTTTTTTCTTTTTCTTTTCTTTTTTTTTTTTTTTT GGACAGAGTCTTGCTCTGTCACCCAGGCTGGAGTGCGGTGGCAGTATCTCAGCTCACCACAACCTCCG CCTCCCGGCTTCAAGTGATTCTCCTGCCTCAGCTTCTCGAGTAGCTGGGACTACAGGCGCGTGCCACC ATGCCCGGCTAATTTTTGTATTTTTAGTAGAGTTGGGGTTTCACCATGTTGGCCAGGATGGCCTCGAA TTTGTGACCTCGTGATCTGCCCCCTCGCCCTCCCGAACTGTTGGGATTACAGGCGTGAGTCACTGTGC CCGGCCTCCTGTCCTGTCTTTTGTTTAATGACTGGGAAAAACATGATACCATGTTGCTTCTCGAGTTG TTTTGTTTTAGTCTTTGGTCTTTGCTAGTAGCTAATAACACGAACTAGTGTTTATCAAGTGCTTTTTA ACTIVE 511192992.1 51 072734.1806 PATENT CACAGAAGGGCTTGGGCTGTGTTCTGCATTTTCTTGTTTAACCCTCTTAAAACTCCTATAAAATGGTA CATATTTTTCTCCCAATTTACAGTCCCTTTAAAGCAAATAATTATAAAAATCCCTATACATGTCACAC AGCTAGATCTGGGATTTCAAATCAGGCCATCAAACAAAGAGTTTATGTACTTAGTAAGTTTTCTGTTC TTTTTCTACAATAGAGTCAGATAGCAAGAAATTACCAAGCCAGGAACCTGAAACAAAACGGACATCAT GTGGGGCTGGGTGGGTGCATGGGCTTTGCAGACTGGACTTTCACTCCAGCTCTTTTAATGATTAGGTG TAAGTGACCTACATTTTGTGAGCAACAGTTTTCTCATCAGCCAACAAAGAATAATTACACCAGATTCA CAGTTATTGAAGAGATAAAGGCATGAATGTGAGATGTCTGGCATAGGGCATCTCATTTAGCAGACACA GAATGAGTACTTGTTTCTGGCTTTTTCTCTCTACATATGCACAAAGAATGCGACTAGAAGCATGGGCT CTAGCCCTGCTCAACTTTCCTCTATTTCCAATACCAAGGGGCTCTGACTTAGGCTGCCACACCAGGCA AGGAGGGCAGTACCACCTCACTTGACCAAGGGCAGGGAGTCACGGACACATCACTTCTTGAGATCCTT TTCCACACCAAGGACTGATGTTTCTGGAATTCTCACTTTATGAAGACAAAACATATAAATGGAAATTT TCTCAGGTAGAGACTCACTCTTGTAGCTCATTGAGTAGGCACTAGTGGTCCACCCCCACTGTCTTTAC TTATTCCTTGACATCACATATCTCTTGCAAAACCTCAAATAATATTAAATGCAATCACCCAATAATAG CATAGCCATAATTAGAGGCATTTAGGAAAGACAGGTGAGTGTGCCACAACTACCTAACACATCAGCAA ATCTGGATTAACCACTTTCTTTGATTTTCCACAATGCAACCTTACTTTTTAATAGTTGGGAATGTTCT AAGTGAATTTAGCAGAGGTTGTTAATCAACTTGAAAGCTGAATTCTGACTTGTCTGACTCTTGGTGGT GCTGGTAGCAGTAGATGTTTACTTTTAGGTTTTGGTGGTGGTGGAATATCACTTCAACGTAAATCATC AGAAATAAGTATTTGTGAACCCCTCTCGCATTAATGTATCTTATTCTGTAAAAAGAACATGTGCAATT TCTCTTAGATACACTACTGCTGCAGCTCACAAACACCTCTGCATATTACATGTACCTCCTCCTGCTCC TCAAGAGTGTGGTCTATTTTGCCATCATCACCTGCTGTCTGCTTAGAAGAACGGCTTTCTGCTGCAAT GGAGAGAAATCATAA[SEQ ID NO: 53] ATAAACAACTTGATGCAGATGTTTCCCCCAAGCCCACTATTTTTCTTCCTTCGATTGCTGAAACAAAA CTCCAGAAGGCTGGAACATACCTTTGTCTTCTTGAGAAATTTTTCCCAGATATTATTAAGATACATTG GCAAGAAAAGAAGAGCAACACGATTCTGGGATCCCAGGAGGGGAACACCATGAAGACTAACGACACAT ACATGAAATTTAGCTGGTTAACGGTGCCAGAAGAGTCACTGGACAAAGAACACAGATGTATCGTCAGA CATGAGAATAATAAAAACGGAATTGATCAAGAAATTATCTTTCCTCCAATAAAGACAGGTATGTGTTT ACACATATCATCTGTCAGAACACTTCTTTGAAAGTGAATGCTGCATTTTTTCCTTTCAGTATTAATGA AAAACATAAATCTTTCTTAAAAATTGTTACATTTAATGGTAGCGTAAATGCCCTGCTACTTTTCTATA GAATTAAAATGGTATAGGTTTTGGAGAAAACAAAATTGAAAAAGTTGCTGAAGGTTTGTCAGCCTCAG CTCCATTATCCAAAATAAGAAAGTCACGTGCTGGTTTTTAGGGTTGTTAGATGGATTAAAGAAACAAC ATACACAGAAGCATCTAGCAACGTGACACGTGGTAAACGCTCAAAAAGTGTTCTCCCTTCTTTTGATG ACTTTACTTGATCAGGAAATAACATATATATGTCTTTCAGGAATGTTCTGCCCAAGCAGGAGAGTCAC TCACCTCAATCTTGCTACCCACAAAGTTTAACCTAAAAACAACGGGTTCATTGTTGACAAAATAATGT TTATCTGAAGATAACTGTAGATCATATTTATCTGTAGATAATGTTTATCTGTGGAGTGTGGCTCTACA AAACATAGAATAGTCTTGGTCACTGCAGTTTTATAGAGGCCTTGGGTTTTTCAGAGTTTCATTTTATA TATCACCATAAAGTAACATTTCATAATTACAGGTTGGTAAGGCTTACATGTACAAACATTCTTCCATT TTCCATAATAAATGCATTTCCTGCCATTGGTGAATGCAGCTCAATAAACATTTATTGTACAATTATGA ACTIVE 511192992.1 52 072734.1806 PATENT CACGCCAGGCTTAGTGGAAATGTGGATGAACAGACAAGGATGAGTTACTGTCCTAAGGATGATGCATG ACAGTGCAGAGAATATACTCTCTTCCTGATCACTCAGGGTCACTCATGATTCATGCGCGAGGTCCCAA AACAGTGCCTTTGATGCAGATTCTGTACATCTCTAGACGATTGGTCCAAGGGCTGAATGTGCTCTGGC CCAGTGGTCCAGTCTGTCACTATATGTCAACATCCTGAATATGAACATAACAGTCCAACATCTCAAGA GTGGGCATGAAAAGGACTCATTTTGTGCTTTTTCCTGTGGTTAACAAGTCCTTTTTAGCCTGGGGGAA CAAGCATTAACAAAATGTTTGAAGATCTTTGCCACGTACCATTCCAAATTTCTAGGGTAAGTCTTTAG CTTTTCAGATCCTGAGTTTCTGCAATGATCAAATGTGATTTGGACAGTTGCGTTGACTTTCTCCTGGG GCTATAATGGAGTGCAAAGGAAACAATGGCAGGGAAAATGCTTGCTTTCAAAATGGTAGCATGGATGT GTTCATTCGTGTAGTTACTGTATTAGGTATAGCCTTTCCTGAAACTAACTGAAGTGGGGTTATAAAAA CAGTCCCAATTTTCTATTTCCTTTGCTGAGACACAAAGAGGAGACAAAAGAGCAAAGCTTGAGGGTAG TTTTACCACTGTGCTTAAGTGTTCTGATTTTTCCAGTGATCAGGGTGAAATAAAAAGCATAGTAAGTT CCAGGGCAGTGAATACCATACAGGAGACAAGTTACAGTTTTATAATGTGTTTTACTTTACACTAAATT CTAAAAGTAAAATGTCTTTTTTTTTTTCCGAGACAGAGTTTCACTCTTGTAGCCCAGGCAGGAGTGCT ATGGTGTGATCTCGGCTCACAGCAACCTCCACCTCCCAGTTTCAAGCGATTCTTCTGCCTCAGCCTCC CGAGAAGTTGAAATTACAGGTGCCTGGCACCATATCTCGCTAATTATTCTATTTTTAGTAGAGATCGG GTTTTACCATGTTGGCCAGGCTGGTCTCGAACTCCTGACTTCAAGTGATCCACCCGCCTCAGCCTCCC AAAGTGCTGGGATTACAGGTGTGAGTCACTGTGCCGGACCTAACAGTAAAATGTCTTTCATGTGCTTC TCAAGGCAACTACATTAAGGAGGACACATCTCTTAATGTCATTCTACAGTAGATTTCTAATGCTCTTT CTTGGAAGTTTGTTTTTCTGAGAAGAGCTAAAAATATAATAACATGGAAGTGATCATATTATATAATC AATGAAGTGCTTTCAAAGGAGATAAAACTAACCTGGTCTGCATTTGCAACCAGCCTTGATTGAGAGAG AGAGAACTCAGGATACACTTAGAGATTTTATTATGGGGAATAGTTACTTTATTCATTTTACCTCAATC AATGCATGGAAATAAGTGACAGTCATTTTCATTTATCTTTTAATAAATAAAGTCACCATGAGGAAAAT GAAAACCCATTAAAGTCAGTCCTTAAAGATATTTGGACATGCAGACATGATAACTAACATTTCCATTC GTGAGACTTACCCAAAACCTATACCTCAAGTCCATTTCTTAGAATACATGAAATAAAGATCTCAGTGA GTGTATAAAACTGCACACCAGAATCATATCCGTATAGACAAGAATACATCTACTAGAAAAATATAAAC CAAAACACCAAGGTGACTCTGTTTTTTTCTGTTTTAAAATATGTTGTCTTTGTATGCATGTTTGCTTC TTCCTTTTTTTTTTTAAACATCGCAGATAAATTCAACTCTCACCTCAGTTGAGAGAGAACTGTCAATG TGACTTGGCCTCTCTCTTTCTAGTCCCAGAAAGAATTGCACTGAAATGCTGAGCTCCTGTAATAAAAA TGACCATTTGCTGAGAGTAATTAACATACTGAAAGAGATTTTCTTAGAATAGTGCACAATGGCCCAAT GGTGACATTATATTGTCTCTTTATAAATTATTTTCTATCTATTTCTGTGGATTATTTCTACAAAGCAC TTTTCATATGTCCAATTCCTTTTATTCCCCTACAAGTACTGACTGACTACTGGCTCTGCTGTTCACTG ATATGACTTTCGGCAAGTTGCCTGCACTTTTTAAACGTTATTTCCTCATTCAGAACATGGGGCCATAC AAAATACAACTCACTTCAGTGTTATTGGGGAATTAAACAAATAAATGCATGGGAAGCATTTAACATAG TGCCTGACACAATAATGAGCACTCAGTAGATGTTAGCTTTTATTAATATTGTTGTTGCTATGTCCAGA AACACTATACCTCCAGAAAATCATGGGTACTTGCTGGGGACGTTGGGGATATGCATGATTTTGAAAGG AGTGACTGCTCTTTACTGCTCAGATGAGAAATTTTTCTAAGCCAGACTCCTTCAAACATGTAAGATTC TGTTGTGGATTCTAGGACTGAAAGAATTCTTGGCCGAGTGTGGTGGCTTATCCTGGTAATCTCATCAT ACTIVE 511192992.1 53 072734.1806 PATENT TTGGGAGGACAAGGCAGGAAGATTGCTTGAGCCCAGGAGTTGGAAACAAGCCTGGACAACATGGCGAA ACCCTGTCTCTACAAAAAATACAAACATTAGCTGGTCATGGGAGTGAGTGCCTGTACTCCCAGCTACT CAGGAGGCTAAGATAGGAGGATCACCTGAGCCTGGGCAGTTTGAGGTTTCAGTGAGCCGTGATGACAC CATACTATACTCCACTCCAGCCTGGGTGACAGTGACATCCTGCCTCAAAAAAACCCCCAAAATTATTC TTTTTGCTGATTTCATGTCAGCAGTGTGTGCTGAAGGCTGTAAAGTAGCCACTTGTTCTGTTTATTTT TCCATTGAACAAGTATTTATCAAAAACGTACTTTGTGGAAGGCACTGTGCTAGGAACTATGCATACAG AAGGAAAACCAAATGTTCTTGGATACTACACTCCAGTTGTGATAAAAAAGAAAAAAGTATTCTTCACA AACTTCAACATTTTGATGTGCAAAAACATAATATATGAATTAGATCTACCTAACTACACAGAATTAGA CCAATTATTTCTGGGATTATGGGCTCATATTTTTAATAACTGTCCTCCTACCTCTCTGTTGACAGGTT TTATAAATATTCATTTAATTACACACAGTCACAGACACACTCAGACACACACACATACACACACACAC ACACCTTGACAAATAATGGGCATGAACAATTGACTGGTACTTGCTCTCATTCTTCTAGATGTCACCAC AGTGGATCCCAAATACAATTATTCAAAGGATGCAAATGGTAAGTTTTTGTGTTTTTTATTTCCTCCTG ATCATTTTAAGTTTTGAACTTCTCTGGCTTGAAAAATCAGGGAATGGATTTTGCTAGGTTGGATGCTG CAGAATGGACCTAATCATATTTTAAATTAGTCCCTCTTTTTCTAGGAGTTGTATTAACAAACCTAACT ACTGCTTCATGTAAGAGATGACTGTAAATTGAAGGGTACAGTGATATGCTTTCAGTTATTTCAAAAAA CAGACTTTACTCATCCATGTGTCTTTTTTCTTTTCTTTTTTTTCTTTTTTGAGACGGAGTCTCGCTCT GTTGAACAGGCTGGATTGCAGTGACGCGATCTCACCTCACTACAACCTCCGCCTCTGGAGTTCAAGCG ATTCTCCAGCCTCAGCTTCTCAAGTAGCTGGGACTACAGGCACATGCCACCATGTCCGGGTCATCTTT GTATTTTTAGCAGAGACCGGGTTTCACTATGTTGGCCAGGCTGGTCTAGAATTCCTGACTTCGTGATC TGCCCCCTCAGCCCTCCGAAGTGCTGGGATTACAGACGTGAGTCACTGTGCCCGGCCTAACAGTAAAA TGTCTTTCATGCGCTTCTCAAGGCAACTACGTTAAGGAGGACACTTCTCTTAATGTCATTCTACAGTA GATTTCTAATGCTCTTTCTTGGAAGTTTGTTTTTCTGAGAAAAGCTAAAAATATAACATGGAAGTGAT CATATTGTATAATCAATGAAGTGCTTTTCAAGGAGATAAAACTAATCTGGTCCACGTTTGCAACCAAC CTTGATTGAGAGAGAGAGAGAACTCAGGATACACTTGGAGATTTTATTATGGGGAATAGTTACTTTAT TCTTTTTTCCTCAATCAATTCATGGAAATAAGTGATAGTCATATTCATTTATCTTTTAATAAATGAAG TCACCATGAGGAAAATAAAAAGACATTGAAAACCCATTAAAGTTAGCCCTTAAAGATATTTGGACATG CAGACTTGATAACTAACGTTTGCATTCTTGAGACTTACCCAAAACCCATACCTCAAGTCCATGTTTTT AGAATTCATGAAATAAAGATCTCAGTGAGTGCATAAAATTGCGCACCAGAATCATATCCGTATAGACA AGAACACATCTACTAGAAAAATAATAAACCAACACACCAATGCAACTGTGTTTTCTTCTGTTTTAAAA TATGTTGTCTTTGTATGCATGTTTGCTTCTTCCTTTTTTTTTTTTAACATCACAGATAAATTCAACTC TCACCTCAGGTTTTATTGAGAGAACTGTCAATGTGACTTGGCCTCTGTCTTTCTAGTCCCAGAAAGAA TCGCACTGAAATGCTGAGCTCCTGTAATAAAAATGACCATTTGCTGAGAGTAATTAACATACTGAAAG AGATTTTCTTAGAGTACACAATGGTGACATTATATTGTCTCTTTATAAATAACTTTCTATCTATTTCT GTGGATTATTCCTACAAAGTACTTTTCATATGTCCAGTTTCTTTTCTTCCCCTACAACTACCGTCTGA ATACTGGCTCTGCTATTTGCTGATATGATTCTCGGCAAGTTGCCTGCACTTTTTAAACTTTATTTCCT CATTCAGAACATGGGGCCATGTAATACTCATGTACGTGAGTATTACGTAATAATGCTCACTTAAGTGT TACTGGGGAATTAAACAAAAAAATGCATGGCAAGCATTTAACATAGTGCCTGACACAATAATGAGCAC ACTIVE 511192992.1 54 072734.1806 PATENT TCAGTAGATGTTAGATTTTATTAATATTGTTGTTGTTATGTCCGGAAACACTATACCTCCAGAAAATC ATGGGTACTTGCTTGGGATGTTGGGGATATGCATGATTTGGAAAGGTATGACTGCTTTTTTCTGCTTA GATGAGAAATTTTTCTAAGCCAGACTCCTTCAAATATGTAAGATTCTGTTGTGGATTCTAGGACGGAA AGAATTCTTGGTCAGGTGTGGTTTCTTATCCCTGTAATCCCAGAATTTTGGGAGGACAAGGCAGGAAG ATTGCTTGAGCCCAGGAGTTTGAAACCAGCCTGGGCAACAAGACGAAACCCTGTCTCTACAAAAGTAC ATAAATTAGCTTGGCTTGGTGGTGTGTGCCTGTATTACCAGCTATTCGGGAGACTGAGATGGGAGGAT CTCCTGAACCTGTGAAGTTTGAGGCTTCAGTGAGCCGTGATGACACCATACTATACTCGACTCCAGCC TGTGCGACAGTGAGACTCTGCGTCAAAAAAAAAACCCCAAAATTATTGTTTTTGCTGATTTCAGGTCA GCAGTGTGTGCTGAAGGGTGTAAAGTAGCCACTTGATCAGTTTATTTTTCCACTGAACAAGTATTTAT CAAAAACATACTTTGTGGTCTGTTTTTGATAAATAAAAAGGCACTGTGCTAGGAGCCATGAATACAGA AGGAAAACCAAATGTTCTTGGATACTACACTCCAGTTGTGATAAAAAAGAAAAATGTATTCTTCACGA ACTTCAACATTTTGATATGCAAAAACATAGTATATAAATTAGATCTACCTGATTACGTAGAATCAGAC CAATTATTTCTGGAATTGAGGGCTCATATTTTTAATAACTGTCCTCCTGCCTCTCTGTTGACAGGTTT TATAAATATTCATTTAATTACACACACACACACACACACCTTGACAAATAATGGACATGAACAATTGA CTAGTACTTGCTCTCATTCTTCTAGATGTCATCACAATGGATCCCAAAGACAATTGGTCAAAAGATGC AAATGGTAAGCTTTTGTGTTTTTCCTTTCCTCCTGATCATTTTAAGTTTTGAACTTCTCTGGCTTGAA AAATCAGGGAATGGGCCGGGTGCGGTGGCTCACGCCTGTAATCCCAGCACTTTGGGAGGCCGAGGCGG GCGGATCACGAGGTCAGGAGATCGAGACCATCCCGGCTAAAACGGTGAAACCCCGTCTCTACTAAAAA TACAAAAAATTAGCCGGGCTTAGTGGCGGGCGCCTGTAGTCCCAGCTACTTGGGAGGCTGAGGCAGGA GAATGGCGTGAACCCGGGAGGCGGAGCTTGCAGTGAGCCGAGATTGCGCCACTGCACTCCACTCCAGC GATTTTGCTAGGTTGGATGCTGCAGAATGGACCTAGTGATATTTTAAATTAGTCCCTCTTTTTCTAGG AGTTGTATTAACAAACCTAACTACTGCTTCGGGTATGAGATGACTGTAAATTAGAGGGTACAGTGATA TGCTTTCAGTTATTTCAAAAAACAGACTTTATTCATCCGTCTGTCTTTTTTTTTTTTTTTTTTTTTTT TTTTTGAGACGGAGGAGTCTCACTCTATCACCCAGGCTGGAGTGCAGTGGCGCGATCTCGGCTCACCA TAACCTCCGCCTTACTGGTTCAAGCGATTCTCCAGCCTCAGCTTCTCAAGTAGCTGGGACTACAGGTG CACACCACCATACCTGGCTAATTTTTGTATTTTTAATAGAGATGGGGTTTCACCACGCTGGCCAGGAT GGTCTTGAATTCTTGACCTCGTGATCTGCCCCCTCGGGCTCCCAAACTTCTGGGATTATAGGCGTGAG CCACTGTGCCCGGCCTTCTGTCTTTTGTTATAATGACTGGGGAAAACATGATACCATGTTGCTTCTTG AGTTGTTTTGTTTTAGTCTTTGGTCTTTGCTAGTAGCTAATAACACGAACTAGTGTTTATCAAGTGCT TTTTACACAGAAGGGCTTGTTCTGCATTTTCTAGTTTAATCATCTTAATACTCCTATAAAGTAGTACA ATATATTTTCTCCCATTTTACAGTCCCTTTAAAGTAAATAACTATAAAAATCCCTTATACATGTCACA CAGCTAGGTCTGGCATTTCAAATCAGGACATCAAACAAAGAATTCGTGCAGTTACTAAGTCCTCTATT TTTTCTACAATAGAAAAAATAGCAAGAATTACAGATAGCAAGACATTACAAGGCAGGAATCTGAAACG AAAGGGACATAATGTGGGGCTGGGTGGGTGCATGAGCTTTGCAGACTAGACTTTCATTCCAGCTCTTT TAATGATTAGGTGTAAGTGACCTACATTTTGTGAGTAACAGTTTTCTCATCAGCCAACTAAGAATAAT TACACCAGATTCACAGTTATTGAAGAGATAAGGGCATGAATGTGAGATGTCTGGCGTAGGGTATCTCA ACTIVE 511192992.1 55 072734.1806 PATENT TTTAGCAGACACAGAATGAATACTTGTTTCTGGCTTTTTCTCTCTACATATGCACAAAGAATGTGACT AGAAGCATTGGCTCTAGCCCTGCTCAACTTTCCTCTATTTCCAATACCAAGGGGCTCTGACTTAGGCT GCCACACCAGGCAAGGAGGGGCAGTACCACCTCACTTGACCAAGGGCAGGGAGTCACGGACACATCAC TTCCTGAGATCCTTTTCCACACCAAGGACTGATGTTTCTGGAATTCTCACTTTATGAAGACAAAACAT ATAAATGGAAATTTCTGCAGGAAGAGACTCACTCTTGTAGCTCATTGAGTAGGCACTAGTGGTCCACC CCCACTGTCTTTACTTATTCCTTGACATCACATATCTCTTGTAAAACCTCAAATAATGTTAAATGCAA TCACCCAATAATAGCATAGCCATAATTAGAGGCATTTAGGAAAGACAGGTGAGTGTGCCACAACTACC TAACACATCAGCAAATCTGGATTAACCACTTTCTTTGATTTTCCACAATGCAACCTTACTTTTTAATA GTTGGGAATGTTCTAAGTGAATTTAGCAGAGGTTGTTAATCAACTTGAAAGCTGAATTCTGACTTGTC TGACTCTTGGTGGTGCTGGTAGCAGTAGATGTTTACTTTTAGGTTTTGGTGGTGGTGGAATATCACTT CAACGTAAATCATCAGAAATAAGTATTTGTGAACCCCTCTCGCATTAATATATCTTATTCTGTAAAAA GAACATGTGCAATTTCTCTTAGATACACTACTGCTGCAGCTCACAAACACCTCTGCATATTACACGTA CCTCCTCCTGCTCCTCAAGAGTGTGGTCTATTTTGCCATCATCACCTGCTGTCTGCTTAGAAGAACGG CTTTCTGCTGCAATGGAGAGAAATCATAA [SEQ ID NO: 54] In certain embodiments, the first antigen binding chain or the second antigen binding chain comprises a constant domain comprising a native or modified TRDC polypeptide. In certain embodiments, the TRDC polypeptide comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 55, which is provided below. In certain embodiments, the TRDC polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 55. SQPHTKPSVFVMKNGTNVACLVKEFYPKDIRINLVSSKKITEFDPAIVISPSGKYNAVKLGKYEDSNS VTCSVQHDNKTVHSTDFEVKTDSTDHVKPKETENTKQPSKSCHKPKAIVHTEKVNMMSLTVLGLRMLF AKTVAVNFLLTAKLFFL [SEQ ID NO: 55] In certain embodiments, the TCR-like fusion molecule comprises a hinge / spacer region that links the first antigen binding chain to the constant domain. In certain embodiments, the TCR-like fusion molecule comprises a hinge / spacer region that links the second antigen binding chain to the constant domain. The hinge / spacer region can be flexible enough to allow the antigen binding chain to orient in different directions to facilitate antigen recognition. In certain embodiments, the hinge / spacer region can be the hinge region from IgG1, the CH2CH3region of immunoglobulin and portions of CD3, a portion of a TCRα polypeptide, a portion of a TCRβ polypeptide, a portion of a CD28 polypeptide, a portion of a CD8 polypeptide, or asynthetic spacer sequence. In certain embodiments, the hinge / spacer region comprises aportion of a TCRα polypeptide. In certain embodiments, the hinge / spacer region comprises a portion of the variable region (TRAV), a portion of the diversity region (TRAD), a portion of ACTIVE 511192992.1 56 072734.1806 PATENT the joining region (TRAJ), a portion of the constant region (TRAC), or a combination thereof. In certain embodiments, the hinge / spacer region comprises a portion of the TRAJ region and a portion of the TRAC region of the TCRα polypeptide. In certain embodiments, the hinge / spacer region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 56. In certain embodiments, the hinge / spacer region comprises or consists of amino acids 1 to 3 of the sequence set forth in SEQ ID NO: 56. An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 56 is set forth in SEQ ID NO: 57. SEQ ID NO: 56 and SEQ ID NO: 57 are provided below. IPNIQNPDPA [SEQ ID NO: 56] ATTCCCAATATCCAGAACCCTGACCCTGCC [SEQ ID NO: 57] In certain embodiments, the hinge / spacer region comprises a portion of a TCRβ polypeptide. In certain embodiments, the hinge / spacer region comprises a portion of the variable region (TRBV), a portion of the diversity region (TRBD), a portion of the joining region (TRBJ), a portion of the constant region (TRBC), or a combination thereof. In certain embodiments, the hinge / spacer region comprises a portion of the TRBJ region and a portion of the TRAC region (C) of the TCRβ polypeptide. In certain embodiments, the hinge / spacer region comprises or consists of the amino acid sequence set forth in SEQ ID NO: 58. In certain embodiments, the hinge / spacer region comprises or consists of amino acid 1 to 2 of the sequence set forth in SEQ ID NO: 58. An exemplary nucleic acid sequence encoding the amino acid sequence of SEQ ID NO: 58 is set forth in SEQ ID NO: 59. SEQ ID NO: 58 and SEQ ID NO: 59 are provided below. LEDLKNVFPPE [SEQ ID NO: 58] CTGGAGGATCTGAAAAACGTGTTCCCTCCTGAA [SEQ ID NO: 59] In certain embodiments, the antigen binding chain does not comprise an intracellular domain. In certain embodiments, the antigen binding chain is capable of associating with a CD3ζ polypeptide. In certain embodiments, the antigen binding chain associating with the CD3ζ polypeptide via the constant domain. In certain embodiments, the CD3ζ polypeptide is endogenous. In certain embodiments, the CD3ζ polypeptide is exogenous. In certain embodiments, binding of the antigen binding chain to a target antigen is capable of activating the CD3ζ polypeptide associated to the antigen binding chain. In certain embodiments, the exogenous CD3ζ polypeptide is fused to or integrated with a costimulatory molecule disclosed herein. ACTIVE 511192992.1 57 072734.1806 PATENT In certain embodiments, the TCR-like fusion molecule comprises an antigen binding chain that comprises an intracellular domain. In certain embodiments, the intracellular domain comprises a CD3ζ polypeptide. In certain embodiments, binding of the antigen binding chain to an antigen is capable of activating the CD3ζ polypeptide of the antigen binding chain. In certain embodiments, the CD3ζ polypeptide comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% homologous to the amino acid sequence set forth in SEQ ID NO: 16 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD3ζ polypeptide comprises or consists of an amino acid sequence that is a consecutive portion of SEQ ID NO: 16, which is at least about 20, or at least about 30, or at least about 40, or at least about 50, and up to about 164 amino acids in length. In certain embodiments, the CD3ζ comprises or consists of the amino acid sequence of amino acids 1 to 164, 1 to 50, 50 to 100, 52 to 164, 100 to 150, or 150 to 164 of SEQ ID NO: 16. In certain embodiments, the CD3ζ polypeptide comprises or consists of amino acids 52 to 164 of SEQ ID NO: 16. In certain embodiments, the CD3ζ polypeptide comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% homologous or identical to SEQ ID NO: 16 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD3ζ polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 16. In certain embodiments, the TCR-like fusion molecule comprises an antigen binding chain that comprises an intracellular domain, wherein the intracellular domain comprises a co- stimulatory signaling region. In certain embodiments, the intracellular domain comprises a co- stimulatory signaling region and a CD3ζ polypeptide. In certain embodiments, the intracellular domain comprises a co-stimulatory signaling region and does not comprise a CD3ζ polypeptide. In certain embodiments, the co-stimulatory signaling region comprises at least an intracellular domain of a co-stimulatory molecule disclosed herein. In certain embodiments, the TCR-like fusion molecule is capable of associating with a CD3 complex (also known as “T-cell co-receptor”). In certain embodiments, the TCR-like fusion molecule and the CD3 complex form an antigen recognizing receptor complex similar to a native TCR / CD3 complex. In certain embodiments, the CD3 complex is endogenous. In certain embodiments, the CD3 complex is exogenous. In certain embodiments, the TCR-like fusion molecule replaces a native and / or an endogenous TCR in the CD3 / TCR complex. In ACTIVE 511192992.1 58 072734.1806 PATENT certain embodiments, the CD3 complex comprises a CD3γ chain, a CD3δ chain, and two CD3ε chains. In certain embodiments, the CD3γ chain comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% homologous or identical to the amino acid sequence having a NCBI reference number: NP_000064.1 (SEQ ID NO: 60) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. SEQ ID NO: 60 is provided below. MEQGKGLAVLILAIILLQGTLAQSIKGNHLVKVYDYQEDGSVLLTCDAEAKNITWFKDGKMIGFLTED KKKWNLGSNAKDPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATISGFLFAEIVSIFVLAVGVYFI AGQDGVRQSRASDKQTLLPNDQLYQPLKDREDDQYSHLQGNQLRRN [SEQ ID NO: 60] In certain embodiments, the CD3δ chain comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% homologous or identical to the amino acid sequence having a NCBI reference numbers: NP_000723.1 (SEQ ID NO: 61) or a fragment thereof, or the amino acid sequence having a NCBI reference numbers: NP_001035741.1 (SEQ ID NO: 62) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. SEQ ID NO: 61 and SEQ ID NO: 62 are provided below. MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLGKRILDPR GIYRCNGTDIYKDKESTVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLALGVFCFAGHETGRLSGA ADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNK [SEQ ID NO: 61] MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLGKRILDPR GIYRCNGTDIYKDKESTVQVHYRTADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNK [SEQ ID NO: 62] In certain embodiments, the CD3ε chain comprises or consists of an amino acid sequence that is at least about 85%, about 90%, about 95%, about 96%, about 97%, about 98%, about 99% or about 100% homologous or identical to the amino acid sequence having a NCBI reference number: NP_000724.1 (SEQ ID NO: 63) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. SEQ ID NO: 63 is provided below. MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGG DEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMDVMSVATIVIV DICITGGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQNKERPPPVPNPDYEPIRKGQRDLYSGLNQ RRI [SEQ ID NO: 63] ACTIVE 511192992.1 59 072734.1806 PATENT In certain embodiments, the TCR-like fusion molecule exhibits a greater antigen sensitivity than a CAR targeting the same antigen. In certain embodiments, the TCR-like fusion molecule is capable of inducing an immune response when binding to an antigen that has a low antigen density on the surface of a tumor cell. In certain embodiments, cells comprising the TCR-like fusion molecule can be used to treat a subject having tumor cells with a low expression level of a surface antigen, e.g., from a relapse of a disease, wherein the subject received treatment which leads to residual tumor cells. In certain embodiments, the tumor cells have a low antigen density of a target molecule on the surface of the tumor cells. In certain embodiments, a target molecule having a low antigen density on the cell surface has a density of less than about 5,000 molecules per cell, less than about 4,000 molecules per cell, less than about 3,000 molecules per cell, less than about 2,000 molecules per cell, less than about 1,500 molecules per cell, less than about 1,000 molecules per cell, less than about 500 molecules per cell, less than about 200 molecules per cell, or less than about 100 molecules per cell. In certain embodiments, a target molecule having a low antigen density on the cell surface has a density of less than about 2,000 molecules per cell. In certain embodiments, a target molecule having a low antigen density on the cell surface has a density of less than about 1,500 molecules per cell. In certain embodiments, a target molecule having a low antigen density on the cell surface has a density of less than about 1,000 molecules per cell. In certain embodiments, a target molecule having a low antigen density on the cell surface has a density of between about 4,000 molecules per cell and about 2,000 molecules per cell, between about 2,000 molecules per cell and about 1,000 molecules per cell, between about 1,500 molecules per cell and about 1,000 molecules per cell, between about 2,000 molecules per cell and about 500 molecules per cell, between about 1,000 molecules per cell and about 200 molecules per cell, or between about 1,000 molecules per cell and about 100 molecules per cell. In certain embodiments, the TCR-like fusion molecule is capable of inducing an immune response when binding to an antigen that is expressed on the surface of a tumor cell having a low tumor cell frequency. In certain embodiments, cells comprising the TCR-like fusion molecule can be used to treat a subject having tumor cells with a low tumor cell frequency, e.g., from a relapse of a disease, wherein the subject received treatment which leads to residual tumor cells. In certain embodiments, the tumor having a low tumor cell frequency has a frequency that is less than about 40% per tumor, less than about 30% per tumor, less than about 20% per tumor, less than about 15% per tumor, less than about 10% per tumor, less than about 5% per tumor, less than about 2% per tumor, or less than about 1% per tumor. In certain embodiments, the low tumor cell frequency is less than about 2% per tumor. In certain ACTIVE 511192992.1 60 072734.1806 PATENT embodiments, the low tumor cell frequency is less than about 1.5% per tumor. In certain embodiments, the low tumor cell frequency is less than about 1% per tumor. In certain embodiments, the low tumor cell frequency is between about 40% per tumor and about 20% per tumor, between about 20% per tumor and about 10% per tumor, between about 15% per tumor and about 10% per tumor, between about 20% per tumor and about 5% per tumor, between about 10% per tumor and about 2% per tumor, or between about 10% per tumor and about 1% per tumor. In certain embodiments, the antigen-recognizing receptor is a TCR-like fusion molecule that comprises a first antigen binding chain comprising a VH of an antibody and a constant domain comprising a TRBC polypeptide; and a second antigen binding chain comprising a VLof an antibody and a constant domain comprising a TRAC polypeptide. In certain embodiments, the first antigen binding chain is designated as “VH-TRBC chain”. In certain embodiments, the second antigen binding chain is designated as “VL-TRAC chain”. In certain embodiments, the first antigen binding chain comprises a hinge region between the VHand the TRBC polypeptide. In certain embodiments, the second antigen binding chain comprises a hinge region between the VL and the TRAC polypeptide. In certain embodiments, the antigen-recognizing receptor is a TCR-like fusion molecule that comprises a first antigen binding chain comprising a VH of an antibody and a constant domain comprising a TRAC polypeptide; and a second antigen binding chain comprising a VL of an antibody and a constant domain comprising a TRBC polypeptide. In certain embodiments, the first antigen binding chain is designated as “VH-TRAC chain”. In certain embodiments, the second antigen binding chain is designated as “VL-TRBC chain”. In certain embodiments, the first antigen binding chain comprises a hinge region between the VH and the TRAC polypeptide. In certain embodiments, the second antigen binding chain comprises a hinge region between the VL and the TRBC polypeptide. In certain embodiments, the antigen-recognizing receptor is a TCR-like fusion molecule that binds to CD19. In certain embodiments, the TCR-like fusion molecule that comprises a first antigen binding chain comprising a VH comprising the amino acid sequence set forth in SEQ ID NO. 76 or SEQ ID NO: 77; and a second antigen binding chain comprising a VL comprising the amino acid sequence set forth in SEQ ID NO.78 or SEQ ID NO: 79. In certain embodiments, the antigen-recognizing receptor is a TCR-like fusion molecule that binds to FcRL5. In certain embodiments, the TCR-like fusion molecule that comprises a first antigen binding chain comprising a VH comprising the amino acid sequence set forth in ACTIVE 511192992.1 61 072734.1806 PATENT SEQ ID NO. 87; and a second antigen binding chain comprising a VLcomprising the amino acid sequence set forth in SEQ ID NO.88.2.2.1. Delivery of the TCR-like fusion molecule In certain embodiments, the TCR-like fusion molecule is delivered to the cell by a viral method. In certain embodiments, the viral method comprises a viral vector. In certain embodiments, the viral vector is a retroviral vector (e.g., a gamma­retroviral vector or a lentiviral vector). Other viral vectors include adenoviral vectors, adeno-associated viral vectors, vaccinia viruses, bovine papilloma viruses, and herpes viruses (e.g., such as Epstein- Barr Virus). In certain embodiments, the TCR-like fusion molecule is delivered to the cell by a non- viral method. Non-limiting examples of non-viral methods encompassed by the presently disclosed subject matter include plasmid, mini-plasmid, nanoplasmids, dsDNA, and ssRNA Any targeted genome editing methods can also be used to deliver the TCR-like fusion molecule to the cell. In certain embodiments, the TCR-like fusion molecule is delivered to the cell by a method comprising homologous recombination, a Zinc finger nuclease, a meganuclease, a Transcription activator-like effector nuclease (TALEN), a Clustered regularly-interspaced short palindromic repeats (CRISPR) system, or a combination thereof. In certain embodiments, a CRISPR system is used to deliver the TCR-like fusion molecule to the cell. In certain embodiments, the cell is a T cell, and the TCR-like fusion molecule is integrated at a locus within the genome of the T cell. Non-limiting examples of loci include a TRAC locus, a TRBC locus, a TRDC locus, and a TRGC locus. In certain embodiments, the locus is a TRAC locus or a TRBC locus. In certain embodiments, the cell is a T cell, and the TCR-like fusion molecule is integrated at a TRAC locus. 2.3. Chimeric Ligand Receptors In certain embodiments, the antigen-recognizing receptor is a chimeric ligand receptor that comprises a ligand or a portion thereof that binds to the first antigen. In certain embodiments, the chimeric ligand receptor further comprises a transmembrane domain and an intracellular signaling domain. In certain embodiments, the transmembrane domain is fused to the ligand or portion thereof. In certain embodiments, the transmembrane domain is fused to the intracellular signaling domain. In certain embodiments, the transmembrane domain is positioned between the ligand or portion thereof and the intracellular signaling domain. In certain embodiments the transmembrane domain of the chimeric ligand receptor is a transmembrane domain ACTIVE 511192992.1 62 072734.1806 PATENT disclosed in Section 2.1.1.2. In certain embodiments, the intracellular signaling domain of the chimeric ligand receptor comprises a CD3ζ polypeptide (e.g., as disclosed in Section 2.1.1.3). Additional information on the presently disclosed chimeric ligand receptor can be found in Sauer et al., Blood (2021) 138 (4): 318–330, the content of which is incorporated by reference in its entirety. 2.4. T Cell Receptors (TCRs) In certain embodiments, a presently disclosed cell comprising an antigen-recognizing receptor further comprises a TCR. A TCR is a disulfide-linked heterodimeric protein consisting of two variable chains expressed as part of a complex with the invariant CD3 chain molecules. A TCR is found on the surface of T cells, and is responsible for recognizing antigens as peptides bound to major histocompatibility complex (MHC) molecules. In certain embodiments, a TCR comprises an alpha chain and a beta chain (encoded by TRA and TRB, respectively). In certain embodiments, a TCR comprises a gamma chain and a delta chain (encoded by TRG and TRD, respectively). Each chain of a TCR is composed of two extracellular domains: Variable (V) region and a Constant (C) region. The Constant region is proximal to the cell membrane, followed by a transmembrane region and a short cytoplasmic tail. The variable region binds to the peptide / MHC complex. The variable domain of both chains each has three complementarity determining regions (CDRs). In certain embodiments, a TCR can form a receptor complex with three dimeric signaling modules CD3δ / ε, CD3γ / ε and CD247 ζ / ζ or ζ / η. When a TCR complex engages with its antigen and MHC (peptide / MHC), the T cell expressing the TCR complex is activated. In certain embodiments, the TCR is an endogenous TCR. In certain embodiments, the TCR is naturally occurring TCR. In certain embodiments, the TCR is an exogenous TCR. In certain embodiments, the TCR is a recombinant TCR. In certain embodiments, the TCR is a non-naturally occurring TCR. In certain embodiments, the non-naturally occurring TCR differs from any naturally occurring TCR by at least one amino acid residue. In certain embodiments, the non-naturally occurring TCR differs from any naturally occurring TCR by at least about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 20, about 25, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100 or more amino acid residues. In certain embodiments, the non-naturally occurring TCR is modified from a naturally occurring TCR by at least one amino acid residue. ACTIVE 511192992.1 63 072734.1806 PATENT In certain embodiments, the non-naturally occurring TCR is modified from a naturally occurring TCR by at least about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 20, about 25, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100 or more amino acid residues. 2.5. Co-stimulatory Ligands In certain embodiments, a presently disclosed cell comprising an antigen-recognizing receptor further comprises at least one recombinant or exogenous co-stimulatory ligand. For example, a presently disclosed cell can be further transduced with at least one co-stimulatory ligand, such that the cell expresses or is induced to express the antigen-recognizing receptor and the at least one co-stimulatory ligand. The at least one co-stimulatory ligand provides a co-stimulation signal to the cell. Non-limiting examples of co­stimulatory ligands include, but are not limited to, members of the tumor necrosis factor (TNF) superfamily, and immunoglobulin (Ig) superfamily ligands. TNF is a cytokine involved in systemic inflammation and stimulates the acute phase reaction. Its primary role is in the regulation of immune cells. Members of TNF superfamily share a number of common features. The majority of TNF superfamily members are synthesized as type II transmembrane proteins (extracellular C-terminus) containing a short cytoplasmic segment and a relatively long extracellular region. Non-limiting examples of TNF superfamily members include nerve growth factor (NGF), CD40L (also known as “CD154”), 4-1BBL, TNF-^, OX40L, CD70, Fas ligand (FasL), CD30L, tumor necrosis factor beta (TNFβ) / lymphotoxin-alpha (LT^), lymphotoxin-beta (LTβ), CD257 / B cell-activating factor (BAFF) / Blys / THANK / Tall-1, glucocorticoid-induced TNF Receptor ligand (GITRL), TNF- related apoptosis-inducing ligand (TRAIL), and LIGHT (TNFSF14). The immunoglobulin (Ig) superfamily is a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells. These proteins share structural features with immunoglobulins – they possess an immunoglobulin domain (fold). Non-limiting examples of immunoglobulin superfamily ligands include CD80, CD86, and ICOSLG. In certain embodiments, the at least one co-stimulatory ligand is selected from the group consisting of 4-1BBL, CD80, CD86, CD70, GITRL, CD40L, OX40L, CD30L, TNFRSF14, ICOSLG, TRAIL, and combinations thereof. In certain embodiments, the cell further comprises one exogenous co-stimulatory ligand that is 4-1BBL. In certain embodiments, the co-stimulatory ligand is human 4-1BBL. In ACTIVE 511192992.1 64 072734.1806 PATENT certain embodiments, the 4-1BBL comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% homologous or identical to the amino acid sequence having a Uniprot Reference No: P41273-1 (SEQ ID NO: 64) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the 4-1BBL comprises or consists of an amino acid sequence that is a consecutive portion of the amino acid sequence of SEQ ID NO: 64. SEQ ID NO: 64 is provided below. MEYASDASLDPEAPWPPAPRARACRVLPWALVAGLLLLLLLAAACAVFLACPWAVSGARASPGSAASP RLREGPELSPDDPAGLLDLRQGMFAQLVAQNVLLIDGPLSWYSDPGLAGVSLTGGLSYKEDTKELVVA KAGVYYVFFQLELRRVVAGEGSGSVSLALHLQPLRSAAGAAALALTVDLPPASSEARNSAFGFQGRLL HLSAGQRLGVHLHTEARARHAWQLTQGATVLGLFRVTPEIPAGLPSPRSE [SEQ ID NO: 64] An exemplary nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 64 is set forth in SEQ ID NO: 65. ATGGAATACGCCTCTGACGCTTCACTGGACCCCGAAGCCCCGTGGCCTCCCGCGCCCCGCGCTCGCGC CTGCCGCGTACTGCCTTGGGCCCTGGTCGCGGGGCTGCTGCTGCTGCTGCTGCTCGCTGCCGCCTGCG CCGTCTTCCTCGCCTGCCCCTGGGCCGTGTCCGGGGCTCGCGCCTCGCCCGGCTCCGCGGCCAGCCCG AGACTCCGCGAGGGTCCCGAGCTTTCGCCCGACGATCCCGCCGGCCTCTTGGACCTGCGGCAGGGCAT GTTTGCGCAGCTGGTGGCCCAAAATGTTCTGCTGATCGATGGGCCCCTGAGCTGGTACAGTGACCCAG GCCTGGCAGGCGTGTCCCTGACGGGGGGCCTGAGCTACAAAGAGGACACGAAGGAGCTGGTGGTGGCC AAGGCTGGAGTCTACTATGTCTTCTTTCAACTAGAGCTGCGGCGCGTGGTGGCCGGCGAGGGCTCAGG CTCCGTTTCACTTGCGCTGCACCTGCAGCCACTGCGCTCTGCTGCTGGGGCCGCCGCCCTGGCTTTGA CCGTGGACCTGCCACCCGCCTCCTCCGAGGCTCGGAACTCGGCCTTCGGTTTCCAGGGCCGCTTGCTG CACCTGAGTGCCGGCCAGCGCCTGGGCGTCCATCTTCACACTGAGGCCAGGGCACGCCATGCCTGGCA GCTTACCCAGGGCGCCACAGTCTTGGGACTCTTCCGGGTGACCCCCGAAATCCCAGCCGGACTCCCTT CACCGAGGTCGGAA [SEQ ID NO: 65] In certain embodiments, the cell further comprises one exogenous co-stimulatory ligand that is CD80. In certain embodiments, the co-stimulatory ligand is human CD80. In certain embodiments, the CD80 comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% homologous or identical to the amino acid sequence having a NCBI Reference No: NP_005182 (SEQ ID NO: 66) or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD80 comprises or ACTIVE 511192992.1 65 072734.1806 PATENT consists of an amino acid sequence that is a consecutive portion of the amino acid sequence of SEQ ID NO: 66. SEQ ID NO: 66 is provided below. MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVATLSCGHNVSVEELAQTRIYWQK EKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLKYEKDAFKREHLAEVTL SVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKL DFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLISVNGIFVICCLTYCFAPRCR ERRRNERLRRESVRPV [SEQ ID NO: 66] An exemplary nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 66 is set forth in SEQ ID NO: 67. SEQ ID NO: 67 is provided below. ATGGGCCACACACGGAGGCAGGGAACATCACCATCCAAGTGTCCATACCTCAATTTCTTTCAGCTCTT GGTGCTGGCTGGTCTTTCTCACTTCTGTTCAGGTGTTATCCACGTGACCAAGGAAGTGAAAGAAGTGG CAACGCTGTCCTGTGGTCACAATGTTTCTGTTGAAGAGCTGGCACAAACTCGCATCTACTGGCAAAAG GAGAAGAAAATGGTGCTGACTATGATGTCTGGGGACATGAATATATGGCCCGAGTACAAGAACCGGAC CATCTTTGATATCACTAATAACCTCTCCATTGTGATCCTGGCTCTGCGCCCATCTGACGAGGGCACAT ACGAGTGTGTTGTTCTGAAGTATGAAAAAGACGCTTTCAAGCGGGAACACCTGGCTGAAGTGACGTTA TCAGTCAAAGCTGACTTCCCTACACCTAGTATATCTGACTTTGAAATTCCAACTTCTAATATTAGAAG GATAATTTGCTCAACCTCTGGAGGTTTTCCAGAGCCTCACCTCTCCTGGTTGGAAAATGGAGAAGAAT TAAATGCCATCAACACAACAGTTTCCCAAGATCCTGAAACTGAGCTCTATGCTGTTAGCAGCAAACTG GATTTCAATATGACAACCAACCACAGCTTCATGTGTCTCATCAAGTATGGACATTTAAGAGTGAATCA GACCTTCAACTGGAATACAACCAAGCAAGAGCATTTTCCTGATAACCTGCTCCCATCCTGGGCCATTA CCTTAATCTCAGTAAATGGAATTTTTGTGATATGCTGCCTGACCTACTGCTTTGCCCCAAGATGCAGA GAGAGAAGGAGGAATGAGAGATTGAGAAGGGAAAGTGTACGCCCTGTA [SEQ ID NO: 67] In certain embodiments, the cell further comprises two exogenous co-stimulatory ligands that are 4-1BBL and CD80. In certain embodiments, the cell further comprises two exogenous co-stimulatory ligands that are 4-1BBL and CD80, wherein the 4-1BBL comprises or consists of the amino acid sequence set forth in SEQ ID NO: 64, and the CD80 comprises or consists of the amino acid sequence set forth in SEQ ID NO: 66. Receptor-comprising cells comprising at least one exogenous co-stimulatory ligand are described in U.S. Patent No.8,389,282, which is incorporated by reference in its entirety. 2.6. Fusion Polypeptides In certain embodiments, a presently disclosed cell comprising an first antigen- recognizing receptor further comprises a fusion polypeptide. For example, a presently disclosed cell can be further transduced with the fusion polypeptide, such that the cell expresses or is induced to express the antigen-recognizing receptor and the fusion polypeptide. The ACTIVE 511192992.1 66 072734.1806 PATENT fusion polypeptide provides a co-stimulation signal to the cell. The fusion polypeptides are capable of enhancing the activity and / or efficacy of a cell comprising the first antigen- recognizing receptor (e.g., a CAR or a TCR-like fusion molecule). In certain embodiments, the fusion polypeptide comprises a) an extracellular domain and a transmembrane domain of a co-stimulatory ligand, and b) an intracellular domain of a first co-stimulatory molecule. Non-limiting examples of the co-stimulatory ligand include tumor necrosis factor (TNF) family members, immunoglobulin (Ig) superfamily members, and combinations thereof. The TNF family member can be selected from the group consisting of 4-1BBL, OX40L, CD70, GITRL, CD40L, and combinations thereof. The Ig superfamily member can be selected from the group consisting of CD80, CD86, ICOS ligand (ICOSLG (also known as “CD275”), and combinations thereof. In certain embodiments, the co-stimulatory ligand is selected from the group consisting of 4-1BBL, OX40L, CD70, GITRL, CD40L, CD80, CD86, ICOSLG, and combinations thereof. In certain embodiments, the fusion polypeptide comprises an extracellular domain and a transmembrane domain of a co-stimulatory ligand that is CD80. In certain embodiments, the co-stimulatory ligand is human CD80. In certain embodiments, the CD80 comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 66 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD80 comprises or consists of an amino acid sequence that is a consecutive portion of the amino acid sequence of SEQ ID NO: 66. In certain embodiments, the extracellular domain of CD80 comprises or consists of an amino acid sequence that is at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to amino acids 1-242 of SEQ ID NO: 66. In certain embodiments, the extracellular domain of CD80 comprises or consists of amino acids 1-242 of SEQ ID NO: 66 or a functional fragment thereof. A functional fragment can be a consecutive portion of amino acids 1-242 of SEQ ID NO: 66, which is at least about 50, at least about 75, at least about 100, at least about 125, at least about 150, at least about 175, or at least about 200, or at least about 220 amino acids in ACTIVE 511192992.1 67 072734.1806 PATENT length. In certain embodiments, the functional fragment retains at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% of the primary function of the extracellular domain of CD80. Non-limiting examples of the primary functions of the extracellular domain of CD80 include binding to / interacting with CD28, binding to / interacting with CTLA-4, binding to / interacting with PD-L1, and contributing to CD80 homodimerization. In certain embodiments, an extracellular domain of CD80 comprises or consists of amino acids 1-242 of SEQ ID NO: 66. In certain embodiments, the transmembrane domain of CD80 comprises or consists of an amino acid sequence that is at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to amino acids 243-263 of SEQ ID NO: 66. In certain embodiments, the transmembrane domain of CD80 comprises or consists of amino acids 243-263 of SEQ ID NO: 66 or a fragment thereof. Such fragment can be at least about 5, at least about 10, at least about 15, or at least about 20 amino acids in length. In certain embodiments, the transmembrane domain of CD80 comprises or consists of amino acids 243-263 of SEQ ID NO: 66. Non-limiting examples of co-stimulatory molecules include CD28, 4-1BB, OX40, ICOS, DAP-10, CD27, CD40, NKG2D, CD2, and combinations thereof. In certain embodiments, the fusion polypeptide comprises an extracellular domain and a transmembrane domain of a co-stimulatory molecule that is 4-1BB. In certain embodiments, the co-stimulatory molecule is human 4-1BB. In certain embodiments, the 4-1BB comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 34 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the 4-1BB comprises or consists of an amino acid sequence that is a consecutive portion of the amino acid sequence of SEQ ID NO: 34. In certain embodiments, the intracellular domain of 4-1BB comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% homologous or identical to amino acids ACTIVE 511192992.1 68 072734.1806 PATENT 214-255 of SEQ ID NO: 34 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the intracellular domain of 4-1BB comprises or consists of amino acids 214-255 of SEQ ID NO: 34 or a functional fragment thereof. Such functional fragment can be a consecutive portion of amino acids 214-255 of SEQ ID NO: 26, which is at least about 20, at least about 25, at least about 30, at least about 35, or at least about 40 amino acids in length. In certain embodiments, the functional fragment of amino acids 214-255 of SEQ ID NO: 34 retains at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% of the primary functions of the intracellular domain of 4-1BB. Non-limiting examples of the primary functions of the intracellular domain of 4-1BB include providing co-stimulatory signaling for the activation and proliferation of an immunoresponsive cell (e.g., a T cell), and interacting and activating downstream adaptors (e.g., TRAFs). In certain embodiments, the intracellular domain of 4-1BB comprises or consists of amino acids 214-255 of SEQ ID NO: 34. In certain embodiments, the co-stimulatory molecule is CD28. In certain embodiments, the co-stimulatory molecule is human CD28. In certain embodiments, the CD28 comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 15 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the CD28 comprises or consists of an amino acid sequence that is a consecutive portion of the amino acid sequence of SEQ ID NO: 15. In certain embodiments, the intracellular domain of CD28 comprises or consists of an amino acid sequence that is at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99%, at least about 100% homologous or identical to amino acids 180 to 219 of SEQ ID NO: 7 or a fragment thereof, and / or may optionally comprise up to one or up to two or up to three conservative amino acid substitutions. In certain embodiments, the intracellular domain of CD28 comprises or consists of amino acids 180 to 219 of SEQ ID NO: 15 or a functional fragment thereof. A functional fragment of amino acids 180 to 219 of SEQ ID NO: 15 can be a consecutive portion of amino acids 180 to 219 of SEQ ID NO: 15, which is at least about 20, at least about 25, at least about 30, or at least about 35 amino acids in length. In certain embodiments, such functional fragment retains at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% of the primary function of the intracellular domain of CD28. Non-limiting examples of the primary functions ACTIVE 511192992.1 69 072734.1806 PATENT of the intracellular domain of CD28 include providing co-stimulatory signaling for the activation and proliferation of an immunoresponsive cell (e.g., a T cell), and interacting with protein adaptors (e.g., PI3K, GRB2, and LCK). In certain embodiments, the intracellular domain of CD28 comprises or consists of amino acids 180 to 219 of SEQ ID NO: 15. In certain embodiments, the fusion polypeptide comprises an intracellular domain of a second co-stimulatory molecule. In certain embodiments, the fusion polypeptide comprises an intracellular domain of a third co-stimulatory molecule. In certain embodiments, the fusion polypeptide comprises an intracellular domain of a fourth co-stimulatory molecule. In certain embodiments, the fusion polypeptide comprises an intracellular domain of a fifth co- stimulatory molecule. In certain embodiments, the first, second, third, fourth, and fifth co- stimulatory molecule can be the same or different among each other. In certain embodiments, the fusion polypeptide comprises an extracellular domain and a transmembrane domain of a co-stimulatory ligand that is CD80, and an intracellular domain of a co-stimulatory molecule that is 4-1BB. In certain embodiments, the fusion polypeptide comprises or consists of an amino acid sequence that is at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 68. In certain embodiments, the fusion polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 71. SEQ ID NO: 68 is provided below. MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVATLSCGHNVSVEELAQTRIYWQK EKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLKYEKDAFKREHLAEVTL SVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKL DFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLISVNGIFVICCLTYCFKRGRK KLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL [SEQ ID NO: 68] In certain embodiments, the fusion polypeptide comprises an extracellular domain and a transmembrane domain of a co-stimulatory ligand that is CD80, an intracellular domain of a first co-stimulatory molecule that is 4-1BB, and an intracellular domain of a second co- stimulatory molecule that is CD28. In certain embodiments, the fusion polypeptide comprises an amino acid sequence that is at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least ACTIVE 511192992.1 70 072734.1806 PATENT about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or at least about 100% homologous or identical to the amino acid sequence set forth in SEQ ID NO: 69. In certain embodiments, the fusion polypeptide comprises or consists of the amino acid sequence set forth in SEQ ID NO: 69. SEQ ID NO: 69 is provided below. MGHTRRQGTSPSKCPYLNFFQLLVLAGLSHFCSGVIHVTKEVKEVATLSCGHNVSVEELAQTRIYWQK EKKMVLTMMSGDMNIWPEYKNRTIFDITNNLSIVILALRPSDEGTYECVVLKYEKDAFKREHLAEVTL SVKADFPTPSISDFEIPTSNIRRIICSTSGGFPEPHLSWLENGEELNAINTTVSQDPETELYAVSSKL DFNMTTNHSFMCLIKYGHLRVNQTFNWNTTKQEHFPDNLLPSWAITLISVNGIFVICCLTYCFRSKRS RLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFP EEEEGGCEL [SEQ ID NO: 69] Various modified fusion polypeptides are disclosed in International Patent Application No. PCT / US2020 / 042753 and in International Patent Application No. PCT / US2024 / 026787, each of which is incorporated by reference hereby in its entirety. 2.7. Gene Disruptions and Gene Modifications In certain embodiments, a presently disclosed cell comprising an antigen-recognizing receptor further comprises a gene disruption of a TRAC locus. In certain embodiments, the gene disruption of the TRAC locus results in a non-functional TCR. In certain embodiments, the gene disruption of the TRAC locus results in knockout of the TCR gene expression. Non-limiting examples of gene disruptions include substitutions, deletions, insertions, or combinations thereof. In certain embodiments, the mutation comprises a missense mutation, a nonsense mutation, or a combination thereof. In certain embodiments, the deletion comprises a non-frameshift deletion, a frameshift deletion, or a combination thereof. In certain embodiments, the insertion comprises a non-frameshift insertion, a frameshift insertion, or a combination thereof. In certain embodiments, the TRAC locus is a human TRAC locus. The gene disruption of the TRAC locus can be generated by any suitable gene editing methods. In certain embodiments, the gene disruption of the TRAC locus (e.g., knockout of the TRAC locus) is generated using a viral method. In certain embodiments, the viral method comprises a viral vector. In certain embodiments, the viral vector is a retroviral vector (e.g., a gammaretroviral vector or a lentiviral vector). Other viral vectors include adenoviral vectors, adena-associated viral vectors, vaccinia viruses, bovine papilloma viruses, and herpes viruses (e.g., such as Epstein-Barr Virus). ACTIVE 511192992.1 71 072734.1806 PATENT In certain embodiments, the gene disruption of the TRAC locus (e.g., knockout of the TRAC locus) is generated using a non-viral method. Non-viral approaches can also be employed for genetic modification of a cell. For example, a nucleic acid molecule can be introduced into a cell by administering the nucleic acid in the presence of lipofection (Feigner et al., Proc. Natl. Acad. Sci. U.S.A. 84:7413, 1987; Ono et al., Neuroscience Letters 17:259, 1990; Brigham et al., Am. J. Med. Sci. 298:278, 1989; Staubinger et al., Methods in Enzymology 101:512, 1983), asialoorosomucoid-polylysine conjugation (Wu et al., Journal of Biological Chemistry 263:14621, 1988; Wu et al., Journal of Biological Chemistry 264:16985, 1989), or by micro-injection under surgical conditions (Wolff et al., Science 247:1465, 1990). Other non-viral means for gene transfer include transfection in vitro using calcium phosphate, DEAE dextran, electroporation, and protoplast fusion. Liposomes can also be potentially beneficial for delivery of DNA into a cell. Transplantation of normal genes into the affected tissues of a subject can also be accomplished by transferring a normal nucleic acid into a cultivatable cell type ex vivo (e.g., an autologous or heterologous primary cell or progeny thereof), after which the cell (or its descendants) are injected into a targeted tissue or are injected systemically. Recombinant receptors can also be derived or obtained using transposases or targeted nucleases (e.g. Zinc finger nucleases, meganucleases, or TALE nucleases, CRISPR). Transient expression may be obtained by RNA electroporation. Any targeted genome editing methods can also be used to generate the gene disruption of the TRAC locus. In certain embodiments, the gene disruption of the TRAC locus is generated by a method comprising homologous recombination, a Zinc finger nuclease, a meganuclease, a Transcription activator-like effector nuclease (TALEN), a Clustered regularly-interspaced short palindromic repeats (CRISPR) system, or a combination thereof. In certain embodiments, a CRISPR system is used to generate the gene disruption of the TRAC locus. Clustered regularly-interspaced short palindromic repeats (CRISPR) system is a genome editing tool discovered in prokaryotic cells. When utilized for genome editing, the system includes Cas9 (a protein able to modify DNA utilizing crRNA as its guide), CRISPR RNA (crRNA, contains the RNA used by Cas9 to guide it to the correct section of host DNA along with a region that binds to tracrRNA (generally in a hairpin loop form) forming an active complex with Cas9), trans-activating crRNA (tracrRNA, binds to crRNA and forms an active complex with Cas9), and an optional section of DNA repair template (DNA that guides the cellular repair process allowing insertion of a specific DNA sequence). CRISPR / Cas9 often employs a plasmid to transfect the target cells. The crRNA needs to be designed for each ACTIVE 511192992.1 72 072734.1806 PATENT application as this is the sequence that Cas9 uses to identify and directly bind to the target DNA in a cell. The repair template carrying CAR expression cassette need also be designed for each application, as it must overlap with the sequences on either side of the cut and code for the insertion sequence. Multiple crRNA's and the tracrRNA can be packaged together to form a single-guide RNA (sgRNA). This sgRNA can be joined together with the Cas9 gene and made into a plasmid in order to be transfected into cells. In certain embodiments, the CRISPR system comprises base editors. In certain embodiments, the CRISPR system comprises transposases / recombinases. In certain embodiments, the CRISPR system comprises prime editors. In certain embodiments, the CRISPR system comprises an epigenetic modulator. In certain embodiments, the CRISPR system comprises is a CRISPRoff system. Additional details on the CRISPR systems of the presently disclosed subject matter can be found in Anzalone et al., Nature biotechnology 38.7 (2020): 824-844 and in Nuñez et al., Cell 184.9 (2021): 2503-2519, the contents of each of which are incorporated by reference in their entireties. In certain embodiments, the TRAC locus is disrupted using a gRNA molecule to knockout expression of TRAC. The gRNA molecule can target a coding sequence of a TRAC gene (e.g., a human TRAC gene) or a non-coding sequence of a TRAC gene (e.g., a human TRAC gene). In certain embodiments, the gRNA molecule targets a coding sequence of a TRAC gene (e.g., a human TRAC gene). In certain embodiments, the gRNA molecule targets a target sequence within a human TRAC gene. In certain embodiments, zinc-finger nucleases are used to generate the gene disruption of the TRAC locus. A zinc-finger nuclease (ZFN) is an artificial restriction enzyme, which is generated by combining a zinc finger DNA-binding domain with a DNA-cleavage domain. A zinc finger domain can be engineered to target specific DNA sequences which allows a zinc- finger nuclease to target desired sequences within genomes. The DNA-binding domains of individual ZFNs typically contain a plurality of individual zinc finger repeats and can each recognize a plurality of basepairs. The most common method to generate new zinc-finger domain is to combine smaller zinc-finger “modules” of known specificity. The most common cleavage domain in ZFNs is the non-specific cleavage domain from the type IIs restriction endonuclease FokI. Using the endogenous homologous recombination (HR) machinery and a homologous DNA template carrying CAR expression cassette, ZFNs can be used to insert the CAR expression cassette into genome. When the targeted sequence is cleaved by ZFNs, the HR machinery searches for homology between the damaged chromosome and the homologous ACTIVE 511192992.1 73 072734.1806 PATENT DNA template, and then copies the sequence of the template between the two broken ends of the chromosome, whereby the homologous DNA template is integrated into the genome. In certain embodiments, a TALEN system is used to generate the gene disruption of the CD70 locus. Transcription activator-like effector nucleases (TALEN) are restriction enzymes that can be engineered to cut specific sequences of DNA. TALEN system operates on almost the same principle as ZFNs. They are generated by combining a transcription activator-like effectors DNA-binding domain with a DNA cleavage domain. Transcription activator-like effectors (TALEs) are composed of 33-34 amino acid repeating motifs with two variable positions that have a strong recognition for specific nucleotides. By assembling arrays of these TALEs, the TALE DNA-binding domain can be engineered to bind desired DNA sequence, and thereby guide the nuclease to cut at specific locations in genome. cDNA expression for use in polynucleotide therapy methods can be directed from any suitable promoter (e.g., the human cytomegalovirus (CMV), simian virus 40 (SV40), or metallothionein promoters), and regulated by any appropriate mammalian regulatory element or intron (e.g. the elongation factor 1a enhancer / promoter / intron structure). For example, if desired, enhancers known to preferentially direct gene expression in specific cell types can be used to direct the expression of a nucleic acid. The enhancers used can include, without limitation, those that are characterized as tissue- or cell-specific enhancers. Alternatively, if a genomic clone is used as a therapeutic construct, regulation can be mediated by the cognate regulatory sequences or, if desired, by regulatory sequences derived from a heterologous source, including any of the promoters or regulatory elements described above. Methods for delivering the genome editing agents / systems can vary depending on the need. In certain embodiments, the components of a selected genome editing method are delivered as DNA constructs in one or more plasmids. In certain embodiments, the components are delivered via viral vectors. Common delivery methods include but is not limited to, electroporation, microinjection, gene gun, impalefection, hydrostatic pressure, continuous infusion, sonication, magnetofection, adeno-associated viruses, envelope protein pseudotyping of viral vectors, replication-competent vectors cis and trans-acting elements, herpes simplex virus, and chemical vehicles (e.g., oligonucleotides, lipoplexes, polymersomes, polyplexes, dendrimers, inorganic Nanoparticles, and cell-penetrating peptides). In certain embodiments, the gene disruption of the TRAC locus can be a disruption of the coding region of the TRAC locus and / or a disruption of the non-coding region of the TRAC locus. In certain embodiments, the gene disruption of the TRAC locus comprises a disruption of the coding region of the TRAC locus. In certain embodiments, the gene disruption of the ACTIVE 511192992.1 74 072734.1806 PATENT TRAC locus comprises an insertion at the coding region of the TRAC locus. Human TRAC protein comprises 4 exons: exon 1, exon 2, exon 3, and exon 4. In certain embodiments, the coding region of the TRAC locus comprises exon 1, exon 2, exon 3, and exon 4. In certain embodiments, the gene disruption of the TRAC locus comprises a disruption at one or more of exon 1 through exon 4 of the TRAC locus. In certain embodiments, the gene disruption of the TRAC locus comprises a disruption at exon 1 of the TRAC locus. In certain embodiments, the gene disruption of the TRAC locus comprises an insertion at exon 1 of the TRAC locus. In certain embodiments, a presently disclosed cell comprising an antigen-recognizing receptor further comprises a gene modification of a TRAC gene. The gene modification of the TRAC gene can result in a non-functional TCR protein or a knockdown of the TCR gene expression. In certain embodiments, the gene modification of the TRAC gene results in knockout of the TCR gene expression. In certain embodiments, the modification of the TRAC gene comprises use of an RNAi agent, including, but not limited to, shRNA, siRNA, LNA, dsRNA, and miRNA. In certain embodiments, the RNAi agent comprises a shRNA. In certain embodiments, the RNAi agent (e.g., shRNA) targets one or more isoforms of the TRAC gene and thereby reduces or eliminates the expression of the TRAC gene or TCR protein. In certain embodiments, the RNAi agent (e.g., shRNA) is expressed from the same construct that expresses the first antigen- recognizing receptor and / or the second antigen-recognizing receptor disclosed herein. In certain embodiments, the expressions of the RNAi agent (e.g., shRNA), the first antigen- recognizing receptor, and the second antigen-recognizing receptor are driven by identical promoters (e.g., a same promoter). In certain embodiments, the expressions of the shRNA, the first antigen-recognizing receptor, and the second antigen-recognizing receptor disclosed herein are driven by different promoters. In certain embodiments, the RNAi agent (e.g., shRNA) comprises a nucleotide sequence that is at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% homologous or identical to at least a portion of a TRAC nucleic acid sequence. In certain embodiments, the RNAi agent (e.g., shRNA) comprises a nucleotide sequence complementary to the TRAC gene that is at least about 10 nucleotides, at least about 15 nucleotides, at least about 20 nucleotides, at least about 25 nucleotides, at least about 30 nucleotides. In certain embodiments, the RNAi agent (e.g., shRNA) comprises a nucleotide sequence that is up to 15 nucleotides, up to 20 nucleotides, up to 25 nucleotides, up to 30 nucleotides, up to 35 nucleotides, up to 40 nucleotides, up to 55 nucleotides, up to 60 ACTIVE 511192992.1 75 072734.1806 PATENT nucleotides, up to 65 nucleotides, up to 70 nucleotides, up to 75 nucleotides, up to 80 nucleotides, up to 85 nucleotides, up to 90 nucleotides, up to 95 nucleotides, or up to 100 nucleotides in length. In certain embodiments, the RNAi agent comprises DNA or atypical or non-naturally occurring residues, for example, but not limited to, phosphorothioate residues. In certain embodiments, the RNAi agent reduces the expression (e.g., endogenous expression) of TCR by about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 100% or any intermediate value or range thereof. In certain embodiments, the RNAi agent reduces the expression (e.g., endogenous expression) of TCR by about 20%. In certain embodiments, the RNAi agent reduces the expression (e.g., endogenous expression) of TCR by about 30%. In certain embodiments, a presently disclosed cell comprising an antigen-recognizing receptor further comprises a gene disruption of a TRBC locus (e.g., a TRBC1 locus, a TRBC2 locus). In certain embodiments, the gene disruption of the TRBC locus (e.g., a TRBC1 locus, a TRBC2 locus) results in a non-functional TCR. In certain embodiments, the gene disruption of the TRBC locus (e.g., a TRBC1 locus, a TRBC2 locus) results in knockout of the TCR gene expression. Any methods to generate the gene disruption of the TRAC locus as disclosed above can be used to generate the gene disruption of the TRBC locus (e.g., a TRBC1 locus, a TRBC2 locus). In certain embodiments, the gene disruption of the TRBC locus is generated by a method comprising a gene editing method comprising homologous recombination, a Zinc finger nuclease, a meganuclease, a Transcription activator-like effector nuclease (TALEN), a Clustered regularly-interspaced short palindromic repeats (CRISPR) system, or a combination thereof. In certain embodiments, the gene disruption of the TRBC locus can be a disruption of the coding region of the TRBC1 locus. In certain embodiments, the gene disruption of the TRBC locus comprises a disruption of the coding region of the TRBC1 locus. In certain embodiments, the gene disruption of the TRBC locus comprises an insertion at the coding region of the TRBC1 locus. Human TRBC1 protein comprises 4 exons: exon 1, exon 2, exon 3, and exon 4. In certain embodiments, the coding region of the TRBC1 locus comprises exon 1, exon 2, exon 3, and exon 4. In certain embodiments, the gene disruption of the TRBC locus comprises a disruption at one or more of exon 1 through exon 4 of the TRBC1 locus. In certain embodiments, the gene disruption of the TRBC locus comprises a disruption at exon 1 of the TRBC1 locus. In certain embodiments, the gene disruption of the TRBC locus comprises an insertion at exon 1 of the TRBC1 locus. ACTIVE 511192992.1 76 072734.1806 PATENT In certain embodiments, the gene disruption of the TRBC locus can be a disruption of the coding region of the TRBC2 locus. In certain embodiments, the gene disruption of the TRBC locus comprises a disruption of the coding region of the TRBC2 locus. In certain embodiments, the gene disruption of the TRBC locus comprises an insertion at the coding region of the TRBC2 locus. Human TRBC2 protein comprises 4 exons: exon 1, exon 2, exon 3, and exon 4. In certain embodiments, the coding region of the TRBC2 locus comprises exon 1, exon 2, exon 3, and exon 4. In certain embodiments, the gene disruption of the TRBC locus comprises a disruption at one or more of exon 1 through exon 4 of the TRBC2 locus. In certain embodiments, the gene disruption of the TRBC locus comprises a disruption at exon 1 of the TRBC2 locus. In certain embodiments, the gene disruption of the TRBC locus comprises an insertion at exon 1 of the TRBC2 locus. In certain embodiments, a presently disclosed cell comprising an antigen-recognizing receptor further comprises a gene modification of a TRBC gene. The gene modification of the TRBC gene can result in a non-functional TCR protein or a knockdown of the TCR gene expression. In certain embodiments, the gene modification of the TRBC gene results in knockout of the TCR gene expression. In certain embodiments, the modification of the TRBC gene comprises use of an RNAi agent, including, but not limited to, shRNA, siRNA, LNA, dsRNA, and miRNA. In certain embodiments, the RNAi agent comprises a shRNA. In certain embodiments, the RNAi agent (e.g., shRNA) targets one or more isoforms of the TRBC gene and thereby reduces or eliminates the expression of the TRBC gene or TCR protein. In certain embodiments, the RNAi agent (e.g., shRNA) is expressed from the same construct that expresses the first antigen- recognizing receptor and / or the second antigen-recognizing receptor disclosed herein. In certain embodiments, the expressions of the RNAi agent (e.g., shRNA), the first antigen- recognizing receptor, and the second antigen-recognizing receptor are driven by identical promoters (e.g., a same promoter). In certain embodiments, the expressions of the shRNA, the first antigen-recognizing receptor, and the second antigen-recognizing receptor disclosed herein are driven by different promoters. In certain embodiments, the RNAi agent (e.g., shRNA) comprises a nucleotide sequence that is at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% homologous or identical to at least a portion of a TRBC nucleic acid sequence. In certain embodiments, the RNAi agent (e.g., shRNA) comprises a nucleotide sequence complementary to the TRBC gene that is at least about 10 nucleotides, at least about ACTIVE 511192992.1 77 072734.1806 PATENT 15 nucleotides, at least about 20 nucleotides, at least about 25 nucleotides, at least about 30 nucleotides. In certain embodiments, the RNAi agent (e.g., shRNA) comprises a nucleotide sequence that is up to 15 nucleotides, up to 20 nucleotides, up to 25 nucleotides, up to 30 nucleotides, up to 35 nucleotides, up to 40 nucleotides, up to 55 nucleotides, up to 60 nucleotides, up to 65 nucleotides, up to 70 nucleotides, up to 75 nucleotides, up to 80 nucleotides, up to 85 nucleotides, up to 90 nucleotides, up to 95 nucleotides, or up to 100 nucleotides in length. In certain embodiments, the RNAi agent comprises DNA or atypical or non-naturally occurring residues, for example, but not limited to, phosphorothioate residues. In certain embodiments, the RNAi agent reduces the expression (e.g., endogenous expression) of TCR by about 5%, about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, about 100% or any intermediate value or range thereof. In certain embodiments, the RNAi agent reduces the expression (e.g., endogenous expression) of TCR by about 60%. 3. Nucleic Acids and Vectors The presently disclosed subject matter provides nucleic acids comprising a polynucleotide encoding an antigen recognizing receptor disclosed herein (e.g., disclosed in Section 2.1). Also provided are cells comprising such nucleic acids. In certain embodiments, the nucleic acid further comprises a promoter that is operably linked to the antigen recognizing receptor disclosed herein. In certain embodiments, the first promoter is endogenous or exogenous. In certain embodiments, the exogenous promoter is selected from an elongation factor (EF)-1 promoter, a CMV promoter, a SV40 promoter, a PGK promoter, and a metallothionein promoter. In certain embodiments, the first promoter is inducible. In certain embodiments, the inducible promoter is selected from an NFAT transcriptional response element (TRE) promoter, a CD69 promoter, a CD25 promoter, and an IL-2 promoter. In certain embodiments, the polynucleotide is integrated at a locus within the genome of the T cell, e.g., a TRAC locus, a TRBC locus, a TRDC locus, or a TRGC locus. In certain embodiments, the locus is a TRAC locus. In certain embodiments, the expression of the fusion polypeptide is under the control of an endogenous promoter. In certain embodiments, the expression of the fusion polypeptide and the antigen-recognizing receptor is under the control of an endogenous promoter. Non-limiting examples of endogenous promoters include an endogenous TRAC promoter, an endogenous TRBC promoter, an endogenous TRDC ACTIVE 511192992.1 78 072734.1806 PATENT promoter, and an endogenous TRGC promoter. In certain embodiments, the endogenous promoter is an endogenous TRAC promoter. In certain embodiments, the nucleic acid is included in a vector. In certain embodiments, the vector is a retroviral vector (e.g., a gamma­retroviral vector or a lentiviral vector). In certain embodiments, the vector is viral vectors selected from the group consisting of adenoviral vectors, adena-associated viral vectors, vaccinia viruses, bovine papilloma viruses, and herpes viruses (e.g., such as Epstein-Barr Virus). In certain embodiments, the vector is a retroviral vector. Retroviral vectors encompassed by the presently disclosed subject matter include, for example and without any limitation, murine leukemia virus (MLV), human T-cell leukemia virus (HTLV), mouse mammary tumour virus (MMTV), Rous sarcoma virus (RSV), Fujinami sarcoma virus (FuSV), Moloney murine leukemia virus (Mo MLV), FBR murine osteosarcoma virus (FBR MSV), Moloney murine sarcoma virus (Mo-MSV), Abelson murine leukemia virus (A-MLV), Avian myelocytomatosis virus-29 (MC29) and Avian erythroblastosis virus (AEV). In certain embodiments, the vector is a lentiviral vector. Lentiviral vectors encompassed by the presently disclosed subject matter include vectors selected from or derived from, for example and without any limitation, human immunodeficiency virus (HIV), simian immunodeficiency virus (SIV), visna / maedi virus (VMV), caprine arthritis-encephalitis virus (CAEV), equine infectious anaemia virus (EIAV), feline immunodeficiency virus (FIV), Maedi visna virus (MVV), or bovine immunodeficiency virus (BIV). Additional details on lentiviruses encompassed by the presently disclosed subject matter can be found in Coffin et al. (1997) “Retroviruses” Cold Spring Harbor Laboratory Press Eds: JM Coffin, SM Hughes, HE Varmus pp 758-763). In certain embodiments, the vector is an adenoviral vector. Adenoviral vectors encompassed by the presently disclosed subject matter include, for example and without any limitation, adenovirus derived from Ad2, Ad5, Ad12, and Ad40 In certain embodiments, the vector is an adeno-associated viral vector (AAV). AAVs encompassed by the presently disclosed subject matter include, for example and without any limitation, vectors derived from an adeno-associated virus serotype, including without limitation, AAV-1 , AAV-2, AAV-3, AAV-4, AAV-5, AAV-6, AAV-7 and AAV-8. Additionally, the nucleic acids can be administered to subjects or and / delivered into cells by art-known methods or as described herein. Genetic modification of a cell (e.g., a T cell or an NK cell) can be accomplished by transducing a substantially homogeneous cell composition with a recombinant DNA construct. In certain embodiments, a retroviral vector ACTIVE 511192992.1 79 072734.1806 PATENT (either gamma­retroviral or lentiviral) is employed for the introduction of the nucleic acid compositions into the cell. For example, the first polynucleotide and the second polynucleotide can be cloned into a retroviral vector and expression can be driven from its endogenous promoter, from the retroviral long terminal repeat, or from a promoter specific for a target cell type of interest. Non-viral vectors may be used as well. In certain embodiments, when the nucleic acid includes multiple polynucleotides, the nucleic acid can be constructed in a single, multicistronic expression cassette, in multiple expression cassettes of a single vector, or multiple vectors. Examples of elements that create polycistronic expression cassette include, but is not limited to, various viral and non-viral Internal Ribosome Entry Sites (IRES, e.g., FGF-1 IRES, FGF-2 IRES, VEGF IRES, IGF-II IRES, NF-κB IRES, RUNX1 IRES, p53 IRES, hepatitis A IRES, hepatitis C IRES, pestivirus IRES, aphthovirus IRES, picornavirus IRES, poliovirus IRES, and encephalomyocarditis virus IRES) and cleavable linkers (e.g., 2A peptides, e.g., P2A, T2A, E2A and F2A peptides). Combinations of retroviral vectors and an appropriate packaging line are also suitable, where the capsid proteins will be functional for infecting human cells. Various amphotropic virus- producing cell lines are known, including, but not limited to, PA12 (Miller, et al. (1985) Mol. Cell. Biol.5:431-437); PA317 (Miller, et al. (1986) Mol. Cell. Biol.6:2895-2902); and CRIP (Danos, et al. (1988) Proc. Natl. Acad. Sci. USA 85:6460-6464). Non-amphotropic particles are suitable too, e.g., particles pseudotyped with VSVG, RD114, or GALV envelope and any other known in the art. Possible methods of transduction also include direct co-culture of the cells with producer cells, e.g., by the method of Bregni, et al. (1992) Blood 80:1418-1422, or culturing with viral supernatant alone or concentrated vector stocks with or without appropriate growth factors and polycations, e.g., by the method of Xu, et al. (1994) Exp. Hemat.22:223-230; and Hughes, et al. (1992) J. Clin. Invest.89:1817. Other transducing viral vectors can be used to modify a cell. In certain embodiments, the chosen vector exhibits high efficiency of infection and stable integration and expression (see, e.g., Cayouette et al., Human Gene Therapy 8:423-430, 1997; Kido et al., Current Eye Research 15:833-844, 1996; Bloomer et al., Journal of Virology 71:6641-6649, 1997; Naldini et al., Science 272:263-267, 1996; and Miyoshi et al., Proc. Natl. Acad. Sci. U.S.A.94:10319, 1997). Other viral vectors that can be used include, for example, adenoviral, lentiviral, and adena-associated viral vectors, vaccinia virus, a bovine papilloma virus, or a herpes virus, such as Epstein-Barr Virus (also see, for example, the vectors of Miller, Human Gene Therapy 15- 14, 1990; Friedman, Science 244:1275-1281, 1989; Eglitis et al., BioTechniques 6:608-614, ACTIVE 511192992.1 80 072734.1806 PATENT 1988; Tolstoshev et al., Current Opinion in Biotechnology 1:55-61, 1990; Sharp, The Lancet 337:1277-1278, 1991; Cornetta et al., Nucleic Acid Research and Molecular Biology 36:311- 322, 1987; Anderson, Science 226:401-409, 1984; Moen, Blood Cells 17:407-416, 1991; Miller et al., Biotechnology 7:980-990, 1989; LeGal La Salle et al., Science 259:988-990, 1993; and Johnson, Chest 107:77S- 83S, 1995). Retroviral vectors are particularly well developed and have been used in clinical settings (Rosenberg et al., N. Engl. J. Med 323:370, 1990; Anderson et al., U.S. Pat. No.5,399,346). Non-viral approaches can also be employed for genetic modification of a cell. For example, a nucleic acid molecule can be delivered into a cell by administering the nucleic acid in the presence of lipofection (Feigner et al., Proc. Natl. Acad. Sci. U.S.A.84:7413, 1987; Ono et al., Neuroscience Letters 17:259, 1990; Brigham et al., Am. J. Med. Sci. 298:278, 1989; Staubinger et al., Methods in Enzymology 101:512, 1983), asialoorosomucoid-polylysine conjugation (Wu et al., Journal of Biological Chemistry 263:14621, 1988; Wu et al., Journal of Biological Chemistry 264:16985, 1989), or by micro-injection under surgical conditions (Wolff et al., Science 247:1465, 1990). Other non-viral means for gene transfer include transfection in vitro using calcium phosphate, DEAE dextran, electroporation, and protoplast fusion. Liposomes can also be potentially beneficial for delivery of DNA into a cell. Transplantation of normal genes into the affected tissues of a subject can also be accomplished by transferring a normal nucleic acid into a cultivatable cell type ex vivo (e.g., an autologous or heterologous primary cell or progeny thereof), after which the cell (or its descendants) are injected into a targeted tissue or are injected systemically. Transient expression may be obtained by RNA electroporation. Methods for delivering the genome editing agents / systems can vary depending on the need. In certain embodiments, the components of a selected genome editing method are delivered as DNA constructs in one or more plasmids. In certain embodiments, the components are delivered via viral vectors. Common delivery methods include but are not limited to, electroporation, microinjection, gene gun, impalefection, hydrostatic pressure, continuous infusion, sonication, magnetofection, adeno-associated viruses, envelope protein pseudotyping of viral vectors, replication-competent vectors cis and trans-acting elements, herpes simplex virus, and chemical vehicles (e.g., oligonucleotides, lipoplexes, polymersomes, polyplexes, dendrimers, inorganic Nanoparticles, and cell-penetrating peptides). In certain embodiments, the delivery methods include the use of colloids. As used herein, the term “colloid” refers to systems in which there are two or more phases, with one phase (e.g., the dispersed phase) distributed in the other phase (e.g., the continuous phase). ACTIVE 511192992.1 81 072734.1806 PATENT Moreover, at least one of the phases has small dimensions (in the range of about 10−9to about 10−6m). Non-limiting examples of colloids encompassed by the presently disclosed subject matter include macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems (e.g., micelles, liposomes, and lipid nanoparticles). In certain embodiments, the delivery methods include the use of liposomes. The term “liposome,” as used herein, refers to single- or multi-layered spherical lipid bilayer structures produced from lipids dissolved in organic solvents and then dispersed in aqueous media. Experimentally and therapeutically used for delivering an active pharmaceutical ingredient (e.g., nucleic acid compositions disclosed herein) to cells, liposomes fuse with cell membranes so the contents are transferred into the cytoplasm. In certain embodiments, the delivery methods include the use of lipid nanoparticles. As used herein, the term “lipid nanoparticle” refers to a particle having at least one dimension in the order of nanometers (e.g., from about 1 nm to about 1,000 nm) and including at least one lipid. In certain embodiments, the lipid nanoparticles can include an active pharmaceutical ingredient (e.g., nucleic acid compositions disclosed herein) for delivering to cells. The morphology of the lipid nanoparticles can be different from liposomes. While liposomes are characterized by a lipid bilayer surrounding a hydrophilic core, lipid nanoparticles have an electron-dense core where cationic lipids and / or ionizable lipids are organized into inverted micelles around an active pharmaceutical ingredient (e.g., nucleic acid compositions disclosed herein). Additional information on the morphology and properties of lipid nanoparticles and liposomes can be found in Wilczewska, et al., Pharmacological reports 64, no. 5 (2012): 1020-1037; Eygeris et al., Accounts of Chemical Research 55, no.1 (2021): 2-12; Zhang et al., Chemical Reviews 121, no.20 (2021): 12181-12277; and Fan et al., Journal of pharmaceutical and biomedical analysis 192 (2021): 113642. In certain embodiments, the lipid nanoparticles have a mean diameter of from about 30 nm to about 150 nm, from about 40 nm to about 150 nm, from about 50 nm to about 150 nm, from about 60 nm to about 130 nm, from about 70 nm to about 110 nm, from about 70 nm to about 100 nm, from about 80 nm to about 100 nm, from about 90 nm to about 100 nm, from about 70 to about 90 nm, from about 80 nm to about 90 nm, from about 70 nm to about 80 nm, or about 30 nm, 35 nm, 40 nm, 45 nm, 50 nm, 55 nm, 60 nm, 65 nm, 70 nm, 75 nm, 80 nm, 85 nm, 90 nm, 95 nm, 100 nm, 105 nm, 110 nm, 115 nm, 120 nm, 125 nm, 130 nm, 135 nm, 140 nm, 145 nm, or 150 nm. In certain embodiments, the lipid nanoparticles can include a cationic lipid or an ionizable lipid. The term “cationic lipid” refers to lipids including a head group with permanent ACTIVE 511192992.1 82 072734.1806 PATENT positive charges. Non-limiting examples of cationic lipids encompassed by the presently disclosed subject matter include 1,2-di-O-octadecenyl-3-trimethylammonium-propane (DOTMA), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 2,3-dioleyloxy-N-[2- (sperminecarboxamido)ethyl]-N,N-dimethyl-1-propanaminium trifluoroacetate (DOSPA), and ethylphosphatidylcholine (ePC). As used herein, the term “ionizable lipid” refers to lipids that are protonated at low pH and are neutral at physiological pH. The pH-sensitivity of ionizable lipids is particularly beneficial for delivery in vivo (e.g., delivery of nucleic acid compositions disclosed herein), because neutral lipids have less interactions with the anionic membranes of blood cells and, thus, improve the biocompatibility of the lipid nanoparticles. Once trapped in endosomes, ionizable lipids are protonated and promote membrane destabilization to allow the endosomal escape of the nanoparticles. Non-limiting example of ionizable lipids encompassed by the presently disclosed subject matter include tetrakis(8-methylnonyl) 3,3′,3″,3‴- (((methylazanediyl) bis(propane-3,1 diyl))bis (azanetriyl))tetrapropionate; decyl (2- (dioctylammonio)ethyl) phosphate; ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2- hexyldecanoate); bis(2-(dodecyldisulfanyl)ethyl) 3,3′-((3-methyl-9-oxo-10-oxa-13,14-dithia- 3,6-diazahexacosyl)azanediyl)dipropionate; 1,1′-((2-(4-(2-((2-(bis(2- hydroxydodecyl)amino)ethyl) (2-hydroxydodecyl)amino)ethyl) piperazin-1- yl)ethyl)azanediyl) bis(dodecan-2-ol); cKK-E12, 3,6-bis(4-(bis(2- hydroxydodecyl)amino)butyl)piperazine-2,5-dione; (6Z,9Z,28Z,31Z)-heptatriaconta- 6,9,28,31-tetraen-19-yl 4-(dimethylamino) butanoate; hexa(octan-3-yl) 9,9′,9″,9‴,9″″,9‴″- ((((benzene-1,3,5-tricarbonyl)yris(azanediyl)) tris (propane-3,1-diyl)) tris(azanetriyl))hexanonanoate; heptadecan-9-yl 8-((2-hydroxyethyl)(6-oxo-6- (undecyloxy)hexyl)amino) octanoate; and (((3,6-dioxopiperazine-2,5-diyl)bis(butane-4, 1- diyl))bis(azanetriyl))tetrakis(ethane-2,1-diyl) (9Z,9′Z,9″Z,9‴Z,12Z,12′Z,12″Z,12‴Z)-tetrakis (octadeca-9,12-dienoate). Additionally, in certain embodiments, the lipid nanoparticles can include other lipids. For example, but without any limitation, the lipid nanoparticles of the presently disclosed subject matter can include phospholipids, cholesterol, polyethylene glycol (PEG)- functionalized lipids (PEG-lipids). These lipids can improve certain properties of the lipid nanoparticles (e.g., stability, biodistribution, etc.). For example, cholesterol enhances the stability of the lipid nanoparticles by modulating their integrity and rigidity. Non-limiting examples of other lipids present in lipid nanoparticles include cholesterol, DC-cholesterol, β- sitosterol, BHEM-cholesterol, ALC-0159, distearoylphosphatidylcholine (DSPC), ACTIVE 511192992.1 83 072734.1806 PATENT dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylglycerol (DOPG), dipalmitoylphosphatidylglycerol (DPPG), dioleoylphosphatidylethanolamine (DOPE), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoyl-phosphatidylethanolamine (POPE) and dioleoyl-phosphatidylethanolamine 4- (N- maleimidomethyl) -cyclohexane -1 -carboxylate (DOPE-mal), dipalmitoyl phosphatidyl ethanolamine (DPPE), dimyristoylphosphoethanolamine (DMPE), distearoylphosphatidylethanolamine (DSPE), 16-O-monomethyl PE, 16-O-dimethyl PE, 18-1 -trans PE, 1- stearioyl-2-oleoyl-phosphatidyethanol amine (SOPE), and l,2-dielaidoyl-sn- glycero-3- phophoethanolamine (transDOPE). In certain embodiments, the lipid nanoparticles can include a targeting moiety that binds to a ligand. The use of the targeting moieties allows selective delivery of an active pharmaceutical ingredient (e.g., nucleic acid compositions disclosed herein) to target cells expressing the ligand (e.g., T cells). In certain embodiments, the targeting moiety can be an antibody or antigen-binding fragment thereof that binds to a cell surface receptor. For example, but without any limitation, the targeting domain is an antibody or antigen-binding fragment thereof that binds to a receptor expressed on the surface of a T cell (e.g., CD3, CD4, CD8, CD16, CD40L, CD95, FasL, CTLA-4, OX40, GITR, LAG3, ICOS, and PD-1). In certain embodiments, the delivery methods are in vivo delivery methods. In certain embodiments, the delivery methods are ex vivo delivery methods. 4. Formulations and Administration The presently disclosed subject matter provides compositions comprising presently disclosed cells (e.g., disclosed in Section 2). In certain embodiments, the compositions are pharmaceutical compositions that further comprise a pharmaceutically acceptable excipient. Compositions comprising the presently disclosed cells can be conveniently provided as sterile liquid preparations, e.g., isotonic aqueous solutions, suspensions, emulsions, dispersions, or viscous compositions, which may be buffered to a selected pH. Liquid preparations are normally easier to prepare than gels, other viscous compositions, and solid compositions. Additionally, liquid compositions are somewhat more convenient to administer, especially by injection. Viscous compositions, on the other hand, can be formulated within the appropriate viscosity range to provide longer contact periods with specific tissues. Liquid or viscous compositions can comprise carriers, which can be a solvent or dispersing medium containing, for example, water, saline, phosphate buffered saline, polyol (for example, ACTIVE 511192992.1 84 072734.1806 PATENT glycerol, propylene glycol, liquid polyethylene glycol, and the like) and suitable mixtures thereof. Compositions comprising the presently disclosed cells can be provided systemically or directly to a subject for inducing and / or enhancing an immune response to an antigen and / or treating and / or preventing a neoplasm. In certain embodiments, the presently disclosed cells or compositions comprising thereof are directly injected into an organ of interest (e.g., an organ affected by a neoplasm). Alternatively, the presently disclosed cells or compositions comprising thereof are provided indirectly to the organ of interest, for example, by administration into the circulatory system (e.g., the tumor vasculature). Expansion and differentiation agents can be provided prior to, during or after administration of the cells or compositions to increase production of cells in vitro or in vivo. The quantity of cells to be administered can vary for the subject being treated. In certain embodiments, between about 104and about 1010, between about 104and about 107, between about 105and about 107, between about 105and about 109, or between about 106and about 108of the presently disclosed cells are administered to a subject. In certain embodiments, between about 105and about 107of the presently disclosed cells are administered to a subject. More effective cells may be administered in even smaller numbers. Usually, at least about l × l05cells will be administered, eventually reaching about l × l010or more. In certain embodiments, at least about 1×105, about 5×105, about 1×106, about 5×106, about 1×107, about 5×107, about 1×108, or about 5×108of the presently disclosed cells are administered to a subject. In certain embodiments, about 1×105of the presently disclosed cells are administered to a subject. In certain embodiments, about 5×105of the presently disclosed cells are administered to a subject. In certain embodiments, about 1×106of the presently disclosed cells are administered to a subject. The precise determination of what would be considered an effective dose can be based on factors individual to each subject, including their size, age, sex, weight, and condition of the particular subject. Dosages can be readily ascertained by those skilled in the art from this disclosure and the knowledge in the art. The presently disclosed cells and compositions can be administered by any method known in the art including, but not limited to, intravenous administration, subcutaneous administration, intranodal administration, intratumoral administration, intrathecal administration, intrapleural administration, intraosseous administration, intraperitonealadministration, pleural administration, and direct administration to the subject. The presentlydisclosed cells can be administered in any physiologically acceptable vehicle, normally intravascularly, although they may also be introduced into bone or other convenient site where ACTIVE 511192992.1 85 072734.1806 PATENT the cells may find an appropriate site for regeneration and differentiation (e.g., thymus). The cells can be introduced by injection, catheter, or the like. Compositions comprising the presently disclosed cells can be provided systemically or directly to a subject for inducing and / or enhancing an immune response to an antigen and / or treating and / or preventing a neoplasm (e.g., cancer), pathogen infection, or infectious disease. In certain embodiments, the presently disclosed cells, compositions, or nucleic acid compositions are directly injected into an organ of interest (e.g., an organ affected by a neoplasm). Alternatively, the presently disclosed cells, compositions, or nucleic acid compositions are provided indirectly to the organ of interest, for example, by administration into the circulatory system (e.g., the tumor vasculature). Expansion and differentiation agents can be provided prior to, during or after administration of the cells, compositions, or nucleic acid compositions to increase production of the cells (e.g., T cells (e.g., CTL cells) or NK cells) in vitro or in vivo. The presently disclosed compositions can be pharmaceutical compositions comprising the presently disclosed cells or their progenitors and a pharmaceutically acceptable carrier. Administration can be autologous or heterologous. For example, cells, or progenitors can be obtained from one subject, and administered to the same subject or a different, compatible subject. Peripheral blood derived cells or their progeny (e.g., in vivo, ex vivo or in vitro derived) can be administered via localized injection, including catheter administration, systemic injection, localized injection, intravenous injection, or parenteral administration. When administering a therapeutic composition of the presently disclosed subject matter (e.g., a pharmaceutical composition comprising a presently disclosed cell), it can be formulated in a unit dosage injectable form (solution, suspension, emulsion). 5. Methods of Treatment The presently disclosed subject matter is based, at least in part, on the discovery that T cells expressing antigen-recognizing receptors targeting a B cell antigen (e.g., CD19, FcLR5, etc.) can be used in subjects expressing allo-antibodies (e.g., anti-HLA, anti-blood group, and other antibodies). These subjects are particularly susceptible to cytokine release syndrome and other serious, if not fatal, complications in response to gene therapies and adoptive cell therapies. Thus, there is a significant need for developing safe and effective therapies for subjects expressing allo-antibodies. The presently disclosed subject matter provides various methods of using the presently disclosed cells or compositions comprising thereof. The presently disclosed cells and ACTIVE 511192992.1 86 072734.1806 PATENT compositions comprising thereof can be used in a therapy or medicament. For example, the presently disclosed subject matter provides methods for inducing B cell depletion in a subject in need thereof. The presently disclosed cells and compositions comprising thereof can be used for inducing B cell depletion in a subject. The presently disclosed cells and compositions comprising thereof can be used for inducing immune tolerance in a subject by depleting sources of allo-antibodies. The presently disclosed cells and compositions comprising thereof can be used for prolonging the survival of a subject receiving an organ transplantation. The presently disclosed cells, compositions, and nucleic acid compositions can also be used for treating and / or preventing an autoimmune disease in a subject. In certain embodiments, each of the above-noted method comprises administering the presently disclosed cells or a composition (e.g., a pharmaceutical composition) comprising thereof to achieve the desired effect, e.g., palliation of an existing condition or prevention of recurrence. For treatment, the amount administered is an amount effective in producing the desired effect. An effective amount can be provided in one or a series of administrations. An effective amount can be provided in a bolus or by continuous perfusion. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject. As used herein, the term “allo- immunized subject” refers to a subject that presents an immune response to non-self antigens from another human. In allo-immunized subjects, non-self cells are detected and induce the maturation of B cell which produce antibodies targeting the non-self antigens. Clinically, this process is observed in subjects that have received an organ transplant, an HLA-mismatched organ transplant, a blood transfusion, a stem cell transfusion, an HLA-mismatched stem cell transfusion, other cell transfusion, or undergone to a pregnancy with a fetus having a different blood type. Conventionally, allo-immunized subjects cannot receive gene therapies or adoptive cell therapies since these can result in serious complications (e.g., cytokine release syndrome). Indeed, allo-immunized subjects (e.g., subjects who have received an allogeneic HSC transplant) are excluded from treatment with exagamglogene autotemcel, an hematopoietic stem cell-based gene therapy. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has a hemoglobinopathy. As used herein, the term “hemoglobinopathy” or “hemoglobinopathic condition” includes any disorder involving the presence of an abnormal hemoglobin molecule in the blood. Examples of hemoglobinopathies included, but are not limited to, hemoglobin C disease, hemoglobin sickle cell disease (SCD), and sickle cell anemia. Also included are ACTIVE 511192992.1 87 072734.1806 PATENT hemoglobinopathies in which a combination of abnormal hemoglobins are present in the blood (e.g., sickle cell / Hb-C disease). As used herein, the term “sickle cell disease” refers to a group of autosomal recessive genetic blood disorders, which results from mutations in a globin gene and which is characterized by red blood cells that assume an abnormal, rigid, sickle shape. They are defined by the presence of βS-gene coding for a β-globin chain variant in which glutamic acid is substituted by valine at amino acid position 6 of the peptide, and second β-gene that has a mutation that allows for the crystallization of HbS leading to a clinical phenotype. As used herein, the term “sickle cell anemia” refers to a specific form of sickle cell disease in patients who are homozygous for the mutation that causes HbS. Other common forms of sickle cell disease include HbS / β-thalassemia, HbS / HbC and HbS / HbD. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has a thalassemia. As used herein, “thalassemia” refers to a hereditary disorder characterized by defective production of hemoglobin (e.g., quantitative deficit of hemoglobin). Examples of thalassemias include α- and β- thalassemia. β-thalassemias are caused by a mutation in the beta globin chain, and can occur in a major or minor form. In the major form of β-thalassemia, children are normal at birth, but develop anemia during the first year of life. The mild form of β-thalassemia produces small red blood cells and the thalassemias are caused by deletion of a gene or genes from the globin chain. α-thalassemia typically results from deletions involving the HBAl and HBA2 genes. Both of these genes encode α-globin, which is a component (subunit) of hemoglobin. There are two copies of the HBA1 gene and two copies of the HBA2 gene in each cellular genome. As a result, there are four alleles that produce α-globin. The different types of a thalassemia result from the loss of some or all of these alleles. Hb Bart syndrome, the most severe form of a thalassemia, results from the loss of all four α-globin alleles. HbH disease is caused by a loss of three of the four [alpha]-globin alleles. In these two conditions, a shortage of [alpha]-globin prevents cells from making normal hemoglobin. Instead, cells produce abnormal forms of hemoglobin called hemoglobin Bart (Hb Bart) or hemoglobin H (HbH). These abnormal hemoglobin molecules cannot effectively carry oxygen to the body's tissues. The substitution of Hb Bart or HbH for normal hemoglobin causes anemia and the other serious health problems associated with a thalassemia. In certain embodiments, the presently disclosed methods further comprise administering an effective amount of a second therapeutic agent. In certain non-limiting embodiments, the second therapeutic agent is selected from blood transfusions, iron chelation ACTIVE 511192992.1 88 072734.1806 PATENT agents (e.g., deferasirox, deferoxamine), hydroxyurea, crizanlizumab, L-glutamine, hematopoietic stem cell transplantation (e.g., exagamglogene autotemcel, lovotibeglogene autotemcel), sirolimus, thalidomide, luspatercept, or a combination thereof. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received or will receive a transplant. Additionally or alternatively, the presently disclosed subject matter provides methods for reducing the risk of transplant rejection in an allo-immunized recipient subject. As used herein, “transplantation” refers to the process of taking a tissue or organ, called a “transplant” or “graft” from one subject and placing it or them into a (usually) different subject. The subject who provides the transplant is called the “donor” and the subject who received the transplant is called the “recipient.” An organ, or graft, transplanted between two genetically different subjects of the same species is called an “allograft.” A graft transplanted between subjects of different species is called a “xenograft.” Examples of transplanted organs and tissues include, but are not limited to, heart, lungs, kidney, liver, islets, pancreas, and skin. As used herein, the term “transplant rejection,” is defined as functional and / or structural deterioration of an organ or tissue. Transplant rejection can include functional and / or structural deterioration due to an active immune response expressed by the recipient, and independent of non-immunologic causes of organ or tissue dysfunction. Transplant rejection can include donor organ or tissue injury, such as an infection of the transplant organ or tissue. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received a kidney transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive a kidney transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of kidney rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received a lung transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive a lung transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of lung rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received a heart transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B ACTIVE 511192992.1 89 072734.1806 PATENT cell depletion in an allo-immunized subject that will receive a heart transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of heart rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received a liver transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive a liver transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of liver rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received a pancreas transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive a pancreas transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of pancreas rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received a skin transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive a skin transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of skin rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received an HLA-mismatched kidney transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive an HLA- mismatched kidney transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of kidney rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received an HLA-mismatched lung transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive an HLA- mismatched lung transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of lung rejection in an allo-immunized recipient. ACTIVE 511192992.1 90 072734.1806 PATENT In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received an HLA-mismatched heart transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive an HLA- mismatched heart transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of heart rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received an HLA-mismatched liver transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive an HLA- mismatched liver transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of liver rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received an HLA-mismatched pancreas transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive an HLA- mismatched pancreas transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of pancreas rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received an HLA-mismatched skin transplant. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that will receive an HLA- mismatched skin transplant. In certain embodiments, the presently disclosed subject matter provides methods for reducing the risk of skin rejection in an allo-immunized recipient. In certain embodiments, the presently disclosed subject matter provides methods for inducing B cell depletion in an allo-immunized subject that has received or will receive a stem cell transplantation. In certain embodiments, the subject has received or will receive a hematopoietic stem cell transplantation. In certain embodiments, the subject has received or will receive an allogenic stem cell transplantation. In certain embodiments, the subject has received or will receive an allogenic hematopoietic stem cell transplantation. In certain embodiments, the subject has received or will receive an HLA-mismatched hematopoietic stem cell transplantation. In certain embodiments, the subject has received or will receive an HLA- ACTIVE 511192992.1 91 072734.1806 PATENT mismatched allogenic stem cell transplantation. In certain embodiments, the subject has received or will receive an HLA-mismatched allogenic hematopoietic stem cell transplantation. The subjects can have an advanced form of disease, in which case the treatment objective can include mitigation or reversal of disease progression, and / or amelioration of side effects. The subjects can have a history of the condition, for which they have already been treated, in which case the therapeutic objective will typically include a decrease or delay in the risk of recurrence. Further modifications, if desired, can be introduced to the presently disclosed cells to avert or minimize the risks of immunological complications (known as “malignant T-cell transformation”), e.g., graft versus-host disease (GvHD), or when healthy tissues express the same target antigens as the tumor cells, leading to outcomes similar to GvHD. A potential solution to this problem is engineering a suicide gene into the presently disclosed cells. Suitable suicide genes include, but are not limited to, Herpes simplex virus thymidine kinase (hsv-tk), inducible Caspase 9 Suicide gene (iCasp-9), and a truncated human epidermal growth factor receptor (EGFRt) polypeptide. In certain embodiments, the suicide gene is an EGFRt polypeptide. The EGFRt polypeptide can enable T-cell elimination by administering anti- EGFR monoclonal antibody (e.g., cetuximab). EGFRt can be covalently joined to the upstream of the antigen-recognizing receptor. The suicide gene can be included within the vector comprising nucleic acids encoding a presently disclosed antigen-recognizing receptor. In this way, administration of a prodrug designed to activate the suicide gene (e.g., a prodrug (e.g., AP1903 that can activate iCasp-9) during malignant T-cell transformation (e.g., GVHD) triggers apoptosis in the suicide gene-activated cells expressing the presently disclosed antigen- recognizing receptor. The incorporation of a suicide gene into a presently disclosed antigen- recognizing receptor gives an added level of safety with the ability to eliminate the majority of receptor-expressing cells within a very short time period. A presently disclosed cell incorporated with a suicide gene can be pre-emptively eliminated at a given timepoint post the cell infusion, or eradicated at the earliest signs of toxicity. 6. Kits The presently disclosed subject matter provides kits for inducing B cell depletion in a subject. In certain embodiments, the kit comprises an effective amount of presently disclosed cells, a presently disclosed composition, or a presently disclosed nucleic acid composition. In certain embodiments, the kit comprises a sterile container; such containers can be boxes, ampules, bottles, vials, tubes, bags, pouches, blister-packs, or other suitable container forms ACTIVE 511192992.1 92 072734.1806 PATENT known in the art. Such containers can be made of plastic, glass, laminated paper, metal foil, or other materials suitable for holding medicaments. In certain non-limiting embodiments, the kit includes an isolated nucleic acid molecule encoding an antigen-recognizing receptor (e.g., a CAR, a TCR, or a TCR-like fusion molecule) directed toward an antigen of interest in expressible form, which may optionally be comprised in the same or different vectors. If desired, the cells, composition, or nucleic acid composition are provided together with instructions for administering the cells, composition, or nucleic acid composition to an allo-immunized subject. The instructions generally include information about the use of the cell, composition or nucleic acid composition for the depletion of B cells. In certain embodiments, the instructions include at least one of the following: description of the therapeutic agent; dosage schedule and administration for inducing B cell depletion; precautions; warnings; indications; counter-indications; over-dosage information; adverse reactions; animal pharmacology; clinical studies; and / or references. The instructions may be printed directly on the container (when present), or as a label applied to the container, or as a separate sheet, pamphlet, card, or folder supplied in or with the container. EXAMPLES The practice of the present disclosure employs, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are well within the purview of the skilled artisan. Such techniques are explained fully in the literature, such as, “Molecular Cloning: A Laboratory Manual”, second edition (Sambrook, 1989); “Oligonucleotide Synthesis” (Gait, 1984); “Animal Cell Culture” (Freshney, 1987); “Methods in Enzymology” “Handbook of Experimental Immunology” (Weir, 1996); ”Gene Transfer Vectors for Mammalian Cells” (Miller and Calos, 1987); “Current Protocols in Molecular Biology” (Ausubel, 1987); “PCR: The Polymerase Chain Reaction”, (Mullis, 1994); “Current Protocols in Immunology” (Coligan, 1991). These techniques are applicable to the production of the polynucleotides and polypeptides disclosed herein, and, as such, may be considered in making and practicing the presently disclosed subject matter. Particularly useful techniques for particular embodiments will be discussed in the sections that follow. The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the presently disclosed cells and compositions, and are not intended to limit the scope of what the inventors regard as their invention. ACTIVE 511192992.1 93 072734.1806 PATENT Example 1 Recent success of CD19 CARs in systemic lupus erythematosus has sparked enormous interest in exploring the potential of CAR T cells to treat non-tumor diseases. CAR T cells appear to succeed beyond previous iterations of immunosuppression in these diseases. The presently disclosed subject matter presents methods and compositions comprising anti-CD19 CAR T cells for inducing B cell depletion in allo-immunized subjects, which cannot conventionally receive transplants or gene therapies because of life-threatening antibodies (e.g., anti-HLA, anti-blood group, and other antibodies). The presently disclosed subject matter uses immunoresponsive cells (e.g., T cells) expressing a chimeric antigen receptor targeting CD19 and including the 1XX domain. Because of their structural features (e.g., the 1XX domain), these cells are provided with clinical features (e.g., low T cell dose, excellent toxicity profile) and are therefore very well suited for clinical intervention in these settings. The presently disclosed subject matter provides methods of treating allo-immunized subjects including transplant patients (e.g., kidney transplant patients), thalassemia patients, and sickle cell patients. Patients are recruited in a double-blind, randomized, placebo-controlled trial. Eligible participants are randomly allocated to the presently disclosed cells or placebo. A central interactive voice system and interactive web response system, and a permuted block randomization scheme can be used to assign participants randomly to a subject identification number and treatment group, and to provide a masked investigational product kit number. Data are captured in a validated electronic system, and processed (including cleaning, reconciling, and quality control processing) and stored in a controlled access environment. Blood samples are collected during study visits at baseline and weeks 1, 2, 4, 8, 12, 16, 22, and 28 to assess B-cell counts, plasma-cell-specific gene expression, and Ig levels. Data on T-cell subsets can also be collected. Blood samples to assess B-cell counts and plasma-cell- specific gene expression can also be collected during any assessment visit for new or worsening symptoms during the study. B-cell levels in peripheral blood can be measured by flow cytometry using fluorescence-activated cell sorting (FACS), conducted at a central laboratory in the 72 hours after sample collection. Whole blood samples are collected in Streck Cyto-chex cell preservative tubes (Streck, La Vista, NE, USA) and shipped to the central laboratory on the day of collection. A minimum of 100,000 lymphocyte events are acquired. B-lineage cells are counted using CD20 and / or CD19 as a FACS marker. The B-cell subsets that were measured included CD20+B cells and CD19+B cells. ACTIVE 511192992.1 94 072734.1806 PATENT Embodiments of the presently disclosed subject matter From the foregoing description, it will be apparent that variations and modifications may be made to the presently disclosed subject matter to adopt it to various usages and conditions. Such embodiments are also within the scope of the following claims. The recitation of a listing of elements in any definition of a variable herein includes definitions of that variable as any single element or combination (or sub-combination) of listed elements. The recitation of an embodiment herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. All patents and publications mentioned in this specification are herein incorporated by reference to the same extent as if each independent patent and publication was specifically and individually indicated to be incorporated by reference. ACTIVE 511192992.1 95

Claims

072734.1806 PATENT WHAT IS CLAIMED IS:

1. A method of treating an allo-immunized subject, the method comprisingadministering to the subject an effective amount of a cell comprising an antigen-recognizing receptor that targets a B cell antigen.

2. A method of inducing B cell depletion in an allo-immunized subject, the methodcomprising administering to the subject an effective amount of a cell comprising an antigen- recognizing receptor that targets a B cell antigen.

3. A method of treating an allo-immunized subject, the method comprisingadministering to the subject an effective amount of a cell comprising an antigen-recognizing receptor that targets CD19 or FcRL5.

4. A method of inducing B cell depletion in an allo-immunized subject, the methodcomprising administering to the subject an effective amount of a cell comprising an antigen- recognizing receptor that targets CD19 or FcRL5.

5. The method of any one of claims 1-4, wherein the antigen-recognizing receptor is achimeric antigen receptor (CAR) or a TCR-like fusion molecule.

6. The method of claim 5, wherein the antigen-recognizing receptor is a chimericantigen receptor (CAR).

7. The method of any one of claims 1-4, wherein the CAR comprises an extracellularantigen-binding domain that binds to the first antigen, and an intracellular signaling domain that is capable of delivering an activation signal to the cell.

8. The method of claim 7, wherein the intracellular signaling domain of the CARcomprises a CD3ζ polypeptide.

9. The method of claim 8, wherein the CD3ζ polypeptide is a native CD3ζ polypeptideor a modified CD3ζ polypeptide.

10. The method of claim 9, wherein the modified CD3ζ polypeptide comprises a nativeITAM1, an ITAM2 variant consisting of two loss-of-function mutations, and an ITAM3 variant consisting of two loss-of-function mutations.

11. The method of claim 10, wherein the modified CD3ζ polypeptide comprises theamino acid sequence set forth in SEQ ID NO: 30.

12. The method of any one of claims 7-10, wherein the intracellular signaling domain ofthe CAR further comprises at least one costimulatory signaling region.

13. The method of claim 12, wherein the at least one costimulatory signaling regioncomprises at least an intracellular domain of a costimulatory molecule or a portion thereof. ACTIVE 511192992.1 96072734.1806 PATENT14. The method of claim 13, wherein the costimulatory molecule is selected from thegroup consisting of CD28, 4-1BB, OX40, CD27, CD40, CD154, CD97, CD11a / CD18, ICOS, DAP-10, CD2, CD150, CD226, and NKG2D.

15. The method of claim 14, wherein the at least one costimulatory signaling regioncomprises a CD28 polypeptide.

16. The method of claim 15, wherein the costimulatory molecule comprises amino acids180 to 220 of SEQ ID NO: 15.

17. The method of claim 7, wherein the CAR comprises a transmembrane domain.

18. The method of claim 17, wherein the transmembrane domain comprises a CD8polypeptide, a CD28 polypeptide, a CD3ζ polypeptide, a CD4 polypeptide, a 4-1BB polypeptide, a OX40 polypeptide, an ICOS polypeptide, a CTLA-4 polypeptide, a PD-1 polypeptide, a LAG-3 polypeptide, a 2B4 polypeptide, or a BTLA polypeptide.

19. The method of claim 18, wherein the transmembrane domain comprises a CD28polypeptide.

20. The method of claim 5, wherein the antigen-recognizing receptor is a TCR-like fusionmolecule.

21. The method of claim 20, wherein the TCR-like fusion molecule comprises (a) a firstantigen-binding chain comprising an antigen-binding fragment of a heavy chain variable region (VH) of an antibody; and (b) a second antigen-binding chain comprising an antigen- binding fragment of a light chain variable region (VL) of the antibody; wherein the first and second antigen-binding chains (i) each comprise the TRAC polypeptide or the TRBC polypeptide, and (ii) bind to the second antigen, wherein the TCR-like fusion molecule binds to the second antigen in an HLA-independent manner.

22. The method of claim 21, wherein at least one of the TRAC polypeptide and the TRBCpolypeptide is endogenous.

23. The method of claim 21, wherein (a) the first antigen-binding chain comprises anantigen-binding fragment of a VH of an antibody and a TRBC polypeptide, and the second antigen-binding chain comprises an antigen-binding fragment of a VL of the antibody and a TRAC polypeptide; or (b) the first antigen-binding chain comprises an antigen-binding fragment of a VH of an antibody and a TRAC polypeptide, and the second antigen-binding chain comprises an antigen-binding fragment of a VL of the antibody and a TRBC polypeptide.

24. The method of any one of claims 1-4, wherein the antigen-recognizing receptor isencoded by a polynucleotide integrated at a locus within the genome of the cell. ACTIVE 511192992.1 97072734.1806 PATENT25. The method of claim 24, wherein the locus is selected from the group consisting of aTRAC locus, a TRBC locus, a TRDC locus, and a TRGC locus.

26. The method of claim 25, wherein the locus is a TRAC locus or a TRBC locus.

27. The method of claim 26, wherein the locus is a TRAC locus.

28. The method of any one of claims 1-4, wherein the cell further comprises a genedisruption of a TRAC locus or a TRBC locus.

29. The method of any one of claims 1-4, wherein the cell further comprises a genemodification of a TRAC locus and a TRBC locus.

30. The method of any one of claims 1-4, wherein the cell is a cell of the lymphoidlineage or a cell of the myeloid lineage.

31. The method of claim 30, wherein the cell of the lymphoid lineage is a T cell or aNatural Killer (NK) cell.

32. The method of claim 31, wherein the cell is a T cell.

33. The method of claim 32, wherein the T cell is derived from an induced pluripotentstem cell.

34. The method of claim 32, wherein the T cell is a CD8+ T cell.

35. The method of claim 34, wherein the CD8+ T cell is CD4 independent.

36. The method of claim 32, wherein the T cell is selected from the group consisting of acytotoxic T lymphocyte (CTL), a γδ T cell, a tumor-infiltrating lymphocyte (TIL), a regulatory T cell, and a Natural Killer T (NKT) cell.

37. The method of claim 32, wherein the T cell is CD62L+.

38. The method of claim 32, wherein the T cell is CD45RA+.

39. The method of claim 32, wherein the T cell is CD45RA+ and CD62L+.

40. The method of any one of claims 1-4, wherein the cell further comprises at least oneexogenous costimulatory ligand.

41. The method of claim 40, wherein the at least one exogenous costimulatory ligandcomprises CD80.

42. The method of claim 40, wherein the at least one exogenous a costimulatory ligandcomprises 4-1BBL.

43. The method of claim 40, wherein the cell comprises two exogenous costimulatoryligands.

44. The method of claim 43, wherein the at least two exogenous costimulatory ligandscomprise CD80 and 4-1BBL. ACTIVE 511192992.1 98072734.1806 PATENT45. The method of any one of claims 1-4, wherein the cell further comprises a fusionpolypeptide comprising: a) an extracellular domain and a transmembrane domain of a co- stimulatory ligand, and b) an intracellular domain of a first co-stimulatory molecule.

46. The method of claim 45, wherein the co-stimulatory ligand is CD80.

47. The method of claim 45, wherein the first co-stimulatory molecule is 4-1BB.

48. The method of claim 45, wherein the co-stimulatory ligand is CD80 and the first co-stimulatory molecule is 4-1BB.

49. The method of claim 45, wherein the fusion polypeptide comprises the amino acidsequence set forth in SEQ ID NO: 68.

50. The method of claim 45, wherein the fusion polypeptide further comprises anintracellular domain of a second co-stimulatory molecule.

51. The method of claim 50, wherein the second co-stimulatory molecule is CD28.

52. The method of claim 50, wherein the co-stimulatory ligand is CD80, the first co-stimulatory molecule is 4-1BB, and the second co-stimulatory molecule is CD28.

53. The method of claim 50, wherein the fusion polypeptide comprises the amino acidsequence set forth in SEQ ID NO: 69.

54. The method of any one of claims 1-4, wherein the cell is autologous.

55. The method of any one of claims 1-4, wherein the cell is allogeneic.

56. The method of claim 55, wherein the allogenic cell is HLA-negative or HLA-class Inegative.

57. The method of any one of claims 1-4, wherein the subject has a hemoglobinopathy ora thalassemia.

58. The method of claim 57, wherein the hemoglobinopathy is selected from hemoglobinC disease, hemoglobin sickle cell disease (SCD), sickle cell anemia, or hereditary anemia.

59. The method of claim 58, wherein the hemoglobinopathy is sickle cell disease.

60. The method of claim 58, wherein the hemoglobinopathy is sickle cell anemia.

61. The method of claim 57, wherein the thalassemia is selected from thalassemia, β-thalassemia, thalassemia major, thalassemia intermedia, α-thalassemia, or hemoglobin H disease.

62. The method of claim 61, wherein the thalassemia is β-thalassemia.

63. The method of any one of claims 1-4, further comprising administering an effectiveamount of a second therapeutic agent. ACTIVE 511192992.1 99072734.1806 PATENT64. The method of claim 63, wherein the second therapeutic agent is selected from bloodtransfusions, iron chelation agents, hydroxyurea, crizanlizumab, L-glutamine, hematopoietic stem cell transplantation, sirolimus, thalidomide, luspatercept, or a combination thereof.

65. The method of claim 63, wherein the second therapeutic agent is exagamglogeneautotemcel or lovotibeglogene autotemcel.

66. The method of any one of claims 1-4, wherein the subject is recipient or a prospectiverecipient of a transplant.

67. The method of claim 66, wherein the transplant is selected from heart transplant, lungtransplant, kidney transplant, liver transplant, islets transplant, pancreas transplant, or skin transplant.

68. The method of claim 66, wherein the transplant is a kidney transplant.

69. The method of claim 66, wherein the transplant is an HLA-mismatched transplant.

70. The method of claim 66, wherein the transplant is a stem cell transplantation.

71. The method of claim 70, wherein the stem cell transplantation is a hematopoietic stemcell transplantation, an allogenic stem cell transplantation, or an allogenic hematopoietic stem cell transplantation.

72. The method of claim 70, wherein the transplantation is an HLA-mismatchedtransplantation. ACTIVE 511192992.1 100