COMPOSITIONS AND THEIR USE FOR CANCER TREATMENT

Abstract

Compositions are described, e.g., compositions comprising cell therapeutic agents and / or protein therapeutic agents, and methods of using these compositions to treat cancer.

Description

COMPOSITIONS AND METHODS FOR THE TREATMENT OF CANCER CROSS-REFERENCE TO RELATED REQUESTS This application claims priority from each of US Provisional Patent Application Nos. 62 / 249,144 filed October 30, 2015; 62 / 331,010 filed May 3, 2016; and 62 / 396,783 filed September 19, 2016, the complete contents of each of which are hereby incorporated by reference. BACKGROUND OF THE INVENTION Adoptive cell therapy (ACT) is a treatment method in which cells are removed from a donor, cultured and / or manipulated in vitro, and then administered to a patient for the treatment of a disease. A variety of cell types have been used in ACT in an attempt to treat various classes of disorders. For cancer treatment, ACT generally involves the transfer of lymphocytes such as chimeric antigen receptor (CAR) T cells. Using CAR T cells involves identifying an antigen on a tumor cell to which a CAR T cell can bind, but the heterogeneity of the tumor can make antigen identification challenging. Accordingly, there remains a need for improved methods of treating cancer using adoptive cell therapy. BRIEF DESCRIPTION OF THE INVENTION The present invention provides methods and compositions useful for the treatment of cancer and / or for initiating or modulating immune responses. In some embodiments, the present invention provides cellular (eg, immune cell) therapeutics comprising a constitutive expression construct, comprising a promoter operably linked to a gene of interest. In some embodiments, the present invention provides cellular (eg, immune cell) therapeutic agents comprising (i) an antigen-binding receptor, wherein the antigen-binding receptor comprises an antigen-binding domain, an antigen-binding domain transmembrane and a cytosolic signaling domain, and (ii) an inducible expression construct, comprising a promoter operably linked to a gene of interest. Among other things, the present invention encompasses the recognition that a combination of a cellular therapeutic agent described herein and one or more additional therapies (eg, one or more additional cellular therapeutic agents (eg, CAR cells -T, CAR-NK cells, TCR-T cells, TIL cells, allogeneic NK cells and autologous NK cells), antibody-drug conjugate, an antibody and / or a polypeptide described herein), may lead to an enhanced induction of beneficial immune responses, for example a cellular response (e.g. ., T cell activation). In some embodiments, the present disclosure provides methods of treating a subject having a tumor, comprising administering to the subject a cellular therapeutic agent described herein and / or a protein therapeutic agent described herein. In some embodiments, methods further comprise the administration of one or more additional therapies (eg, a second cellular therapeutic agent (eg, CAR-T cells, CAR-NK cells, TCR-T cells, TIL, allogeneic NK cells, and autologous NK cells), an antibody-drug conjugate, an antibody, and / or a polypeptide described herein). Other features, objects, and advantages of the present invention will become apparent from the detailed description that follows. However, it is to be understood that the detailed description, while indicating embodiments of the present invention, is given by way of illustration only, not limitation. Various changes and modifications within the scope of the invention will become apparent to those skilled in the art from the detailed description. BRIEF DESCRIPTION OF THE DRAWINGS The figures in the drawing are for illustrative purposes only, not limiting. Figure 1 is a schematic depicting an illustrative cellular therapeutic agent. Figure 2 is a schematic depicting an exemplary cellular therapeutic agent encoding an inducible scFv-CD19 fusion protein. Figure 3 is a schematic depicting an illustrative cellular therapeutic agent encoding an inducible scFv-EGFR fusion protein. Figure 4 is a schematic depicting an illustrative "self-amplifying" cellular therapeutic agent encoding an inducible scFv-CD19 fusion protein and an inducible CAR that targets CD19. Figure 5 is a schematic depicting an illustrative "self-amplifying" cellular therapeutic agent encoding an inducible scFv-CD19 fusion protein and a constitutively expressed CAR that targets CD19. Figure 6 is a schematic depicting an illustrative "self-amplifying" cellular therapeutic agent expressing an antigen-binding receptor that does not include a signaling domain leading to induction of killing, and that includes a signaling domain sufficient to induce gene transcription and also encoding a fusion protein scFv- Inducible CD19 and an inducible CAR (left) or a constitutively expressed CAR (right) that target CD19. Figure 7 is a schematic depicting an illustrative cellular therapeutic agent encoding various inducible genes. Figure 8 is a schematic depicting an illustrative cellular therapeutic agent encoding an inducible cytokine. Figure 9 is a schematic depicting an illustrative cellular therapeutic agent encoding an inducible scFv-CD30 fusion protein. Figure 10 is a schematic depicting an illustrative cellular therapeutic agent encoding an inducible toxin. Figure 11 is a schematic depicting an illustrative cellular therapeutic agent encoding various inducible genes. Figures 12A, 12B and 12C are schematics depicting illustrative CD19 variants. Figure 13 is a schematic depicting illustrative antibody fusion proteins, in which a polypeptide antigen is fused to the C-terminus of an antibody light chain (LC), a polypeptide antigen is fused to the N-terminus of an LC of an antibody, a polypeptide antigen is fused to the C-terminus of an antibody heavy chain (HC), or a polypeptide antigen is fused to the N-terminus of an antibody HC. Figures 14A and 14B show the expression levels of various antigen polypeptide-antibody fusion constructs. Figure 15 is a schematic depicting illustrative antibody fusion proteins, in which a polypeptide antigen is fused in various orientations to an scFv. Figure 16 shows the expression levels of various antigen polypeptide-scFv fusion constructs. Figures 17A, 17B, 17C and 17D show the binding of panitumumab-CD19 fusion proteins to an anti-CD19 antibody (FMC63). Figure 18 shows the binding of panitumumab-CD19 fusion proteins to an anti-CD19 antibody (FMC63) relative to negative controls. Figures 19A, 19B, 19C and 19D show the binding of LY2875358-CD19 fusion proteins to an anti-CD19 antibody (FMC63). Figure 20 shows the binding of LY2875358-CD19 fusion proteins to an anti-CD19 antibody (FMC63) relative to negative controls. Figure 21 shows the binding of trastuzumab scFv-CD19 fusion proteins to an anti-CD19 antibody (FMC63). Figures 22A, 22B and 22C show the binding of LY2875358-CD19 fusion proteins to cells expressing c-Met and an anti-CD19 antibody (FMC63). Figures 23A and 23B show the binding of trastuzumab scFv-CD19 fusion proteins to an anti-CD19 antibody (FMC63) and to Her-2 protein. Figures 24A-24B show the binding of trastuzumab scFv-CD19 fusion proteins to an anti-CD19 antibody (FMC63) relative to negative controls. Figure 25 shows the binding of captured CD19-scFv fusion proteins on ELISA plates coated with anti-His antibody. Figure 26 shows the binding of captured CD19-scFv fusion proteins on ELISA plates coated with anti-His antibody. Figure 27 shows binding of captured CD19-scFv fusion proteins on anti-FMC63 (anti-CD19) coated plates, then detected with anti-His-HRP. Figure 28 shows the detection of human CD19-anti-Her2 trastuzumab scFv-Fc fusion proteins in a "sandwich ELISA" format. Figure 29 shows the capture of multiple fusion proteins by the anti-CD19 monoclonal antibody FMC63 AND their detection by the HRP-coupled anti-His antibody. Figure 30 shows the scFv Vh-VI-His Leul6 anti-CD20 fusion protein capture of the full-length extracellular domain CD19 by the C-terminal His tag and then detected by the mouse anti-CD19 monoclonal antibody FMC63 and then anti-mouse IgG-HRP. Figure 31 shows the results of fusion proteins incorporating CD22 protein domains, or anti-EGFRvIII scFv (#64: scFv-His CD22-FMC63; #65: scFv-His CD22-anti-CD20; # 67: scFv-his ECD-anti-EGFRvIII complete CD19;#68: scFv-His CD22-anti-EGFRvIII). Figure 32 shows the results for protein-antibody fusion proteins and protein-scFv fusion proteins derived from the same antibody, panitumumab (No. 57: Panitumumab scFv Vh-VI-His from Her2 extracellular domain; no. 58 Her2 extracellular D4 Panitumumab scFv Vh-VI-His; #33+4; (co-transfection of heavy and light chains; one chain carries the CD19 fusion): CD19 extracellular Panitumumab Dl+2 His-antibody) . Figure 33 shows the binding affinity of the purified scFv-His CD19-anti-Her2 fusion protein for the FMC63 antibody. Figure 34 shows the binding affinity of the scFv-His CD19-anti-Her2 fusion protein bound to FMC63 to Her2. Figure 35 shows the binding affinity of the scFv-His CD19-anti-Her2 fusion protein bound to FMC63 to scFv anti-Her2. Figure 36 shows a flow cytometry profile of the scFv fusion protein from CD19-ECD-Leul6 (VH / VL) (#63) bound to 293 cells expressing CD20 and labeled with monoclonal anti-CD19 antibody conjugated to FMC63-PE. Figure 37 shows a flow cytometric profile of CD19-Dl+2-Leul6 (VH / VL) scFv fusion protein (#83) bound to 293 cells expressing CD20 and labeled with conjugated anti-CD19 monoclonal antibody. to FMC63-PE. Figure 38 shows a flow cytometry profile of CD19-DI+2-Leul6 (VL / VH) scFv fusion protein (#85) bound to 293 cells expressing CD20 and labeled with conjugated anti-CD19 monoclonal antibody. to FMC63-PE. Figure 39 shows a flow cytometric profile of CD19-Dl+2-Leul6 (VH / VL)-huIgGFc scFv fusion protein (#82) bound to 293 cells expressing CD20+o-huIgG-FITC. Figure 40 shows the analysis of the anti-huIgG-FITC negative control: 293-CD20 + a-huIgG-FITC. Figure 41 shows a flow cytometry profile of the CD19-Dl+2-Leul6 (VH / VL)-huIgGFc scFv fusion protein (#84) bound to 293 cells expressing CD20+α-huIgG-FITC. Figure 42 shows a flow cytometry profile of CD22-D123-Leul6 (VH / VL) scFv fusion protein (#65) bound to 293 cells expressing CD20 + a-His-PE. Figure 43 shows the detection control for Her2-A431 + Trastuzumab-PE cells, showing the background level of binding (A431 cells are Her2-negative). Figure 44 shows the analysis of A431 + Her2-ECD-scFv-scFv (VH / VL) fusion protein (#57) + Trastuzumab-PE-conjugate. Figure 45 shows the analysis of A431 + Her2-D4-Panitumumab (VH / VL) scFv fusion protein (#58) + Trastuzumab-PE-conjugate. Figure 46 shows the results of the IFNγ ELISA for BT474 cells. coated with the indicated peptide and incubated with CAR-T specific for CD19 at a ratio 10:1 target effector. Figure 47 shows the results of the IFNγ ELISA for BT474 cells. coated with the indicated peptide and incubated with CAR-T specific for CD19 at a ratio 1:1 target effector. Figure 48 shows summary XTT cytotoxicity results for BT474 cells coated with the indicated peptide and incubated with CD19-specific CAR-Ts at a target effector ratio of 10:1. Figure 49 shows the results of the IFN[gamma] ELISA for BT474 cells coated with the indicated peptide and incubated with CAR-T specific for CD19 at a ratio 10:1 target effector. Figure 50 shows the results of the IFN[gamma] ELISA for BT474 cells coated with the indicated peptide and incubated with CD19-specific CAR-Ts at a target effector ratio of 1:1. Figures 51A through 51C show illustrative Fe-based constructs. Figures 52A to 52C show illustrative Fe-based bi-specific constructs. Figures 53A and 53B show illustrative Fe-based constructs that include an Fe Ig "swap." Figures 54A and 54B show illustrative constructs, in which a loop is replaced in one or both Fe CH3 domains. Figure 55 shows an illustrative construct with a masking moiety fused to the constructs described in Figures 52B and 52C with a masking moiety fused to the N-terminus of scFv. Figure 56 shows an illustrative construct with a masking moiety fused to the constructs described in Figures 53B and 53C with the masking moiety fused to the N-terminus of the VH and / or VL in the VH / VL arm. Figure 57 shows an illustrative construct with a masking moiety fused to the construct depicted in Figure 54B with a masking moiety fused to the N-terminus of each of the heavy chains. Figure 58 shows an illustrative construct with a masking moiety fused to the constructs described in Figure 55A and 55B with a masking moiety fused to the N-terminus of a heavy chain and / or the VH of scFv. Figures 59A to 59D show analysis of GFP expression from the CMV promoter-tGFP construct (#66) under resting or activated conditions. Figures 60A to 60D show analysis of GFP expression from the human CD69 promoter-tGFP (#46) under resting or activated conditions. Figures 61A to 61D show analysis of GFP expression from the human TNFalpha-tGFP promoter (#47) under resting or activated conditions. Figures 62A to 62D show analysis of GFP expression from the human NFAT element x 6 promoter-tGFP (#49) under resting or activated conditions. Figures 63A to 63B show analysis of CD69 expression on the surface of cells under resting or activated conditions. Figures 64A through 64D depict the binding of CD19-containing fusion proteins (#42, #43, #56, #82, #83, #91, #92, #93, # 94) to a plate coated with FMC63. Figure 64D shows titer determinations for fusion proteins #82, #83, #91 and #92. Figures 65A to 65D show the capture of multiple fusion proteins by plate-bound antigen and their detection by HRP-coupled anti-His antibody. Figures 66A and 66B show flow cytometry results of CD19-Dl+2-Leul6 scFv fusion protein (VH / VL) (#83) bound to 293 cells expressing CD20 and labeled with monoclonal antibody FMC63- PE anti-His-PE (67A) or anti-CD19 (67B). Figures 67A and 67B show flow cytometry results of CD19-Dl+2-Leul6 (VH / VL)-huIgGFc scFv fusion protein (#82) bound to 293 cells expressing CD20 and labeled with monoclonal antibody or -huIgG-FITC (68A) or anti-CD19 FMC63-PE or FMC63-PE (68B). Figures 68A to 68D show IFNγ ELISA results for fusion protein construct #83. Figure 69A: 24 hrs, 10:1 target effect ratio; Figure 69B: 24h, 2:1 target effect ratio; Figure 69C: 48h, 10:1 effector:target ratio; Figure 69D: 48h, 2:1 target effect ratio. Figure 69 shows the results of the IFN[gamma] ELISA for the fusion protein derived from the co-transfection of construct #33 + construct #4 at 24 h, 2:1 target effect ratio. Figures 70A and 70B show summary XTT cytotoxicity results for fusion protein #83 and 293-CD20 cells. Figure 71A: 48 hrs, 10:1 target effect ratio; Figure 71B 48 h, 2:1 target effect ratio. Figures 71A and 71B show summary XTT cytotoxicity results for fusion protein derived from co-transfection of construct #33 + construct #4 and A4321 cells. Figure 71A: 24h, 10:1 target effect ratio. Figure 71B: 24h, 2:1 target effect ratio. Figures 72A and 72B show HER2 and EGFR expression in transiently transfected 293T cells. Figures 73A to 73D show the binding of fusion protein #43 to cells expressing 293T-Her2. Figures 74A to 74D show the binding of fusion proteins #94 and #95 to cells expressing 293T-Her2. Figures 75A and 75B show the binding of fusion protein #94 to cells expressing 293T-EGFR. Figures 76A and 76B show CAR19-mediated cytotoxicity redirected to HER2+ cells by CAR19 T-cell secretion of fusion protein encoded by construct #42. Figure 77 shows the binding of a heteromeric fusion protein composed of fusion proteins #29 and #103 to FMC63 anti-CD19 antibody detected by HRP-conjugated mouse IgG antibody. Figures 78A and 78B show the yeast surface display of the wild-type CD19 extracellular domain. Figure 79 shows antibody binding to the extracellular domain of CD19 displayed in yeast. Figure 80 demonstrates that combinatorial CD19 libraries efficiently display on the surface of yeast and maintain antibody binding. Figures 81A and 81B demonstrate that combinatorial CD19 libraries can be enriched for EGFR and HER2 binding ligands. Definitions In order that the present invention may be more readily understood, certain terms and expressions are first defined below. Additional definitions for the following terms and expressions and other terms and expressions are set forth throughout the specification. Administration As used herein, the term "administration" refers to the administration of a composition to a subject or system. Administration to an animal subject (eg, a human) may be by any appropriate route. For example, in some embodiments, administration can be bronchial (including bronchial instillation), buccal, enteral, interdermal, intra-arterial, intradermal, intragastric, intramedullary, intramuscular, intranasal, intraperitoneal, intrathecal, intravenous, intraventricular, within a organ-specific (eg, intrahepatic), mucosal, nasal, oral, rectal, subcutaneous, sublingual, topical, tracheal (including by intratracheal instillation), transdermal, vaginal, and vitreal. In some embodiments, administration can be intratumoral or peritumoral. In some embodiments, administration may involve intermittent dosing. In some embodiments, administration may involve continuous dosing (eg, infusion) for at least a selected period of time. Adoptive cell therapy-. As used herein, "adoptive cell therapy" or "ACT" implies the transfer of immune cells with antitumor activity to cancer patients. In some embodiments, ACT is a treatment process that involves the use of lymphocytes with antitumor activity, the in vitro expansion of these cells to large numbers, and their infusion into a cancer-bearing host. Agent: The term "agent" as used herein may refer to a compound or entity of any chemical class including, for example, polypeptides, acids nucleic acids, saccharides, lipids, small molecules, metals, or combinations thereof. As will be apparent from the context, in some embodiments, an agent may be or comprise a cell or organism, or a fraction, extract, or component thereof. In some embodiments, an agent is or comprises a natural product in that it is found in and / or obtained from nature. In some embodiments, an agent is or comprises one or more entities that are human-made, in the sense that they are designed, genetically engineered, and / or produced through the action of human hands and / or it is not found in nature. In some embodiments, an agent can be used in pure or isolated form; in some embodiments, an agent can be used in crude form. In some embodiments, potential agents are provided as collections or banks, for example, that can be screened to identify or characterize active agents within them. Some particular embodiments of agents that can be used in accordance with the present invention include small molecules, antibodies, antibody fragments, aptamers, nucleic acids (eg, siRNA, siRNA, DNA / RNA hybrids, antisense oligonucleotides, ribozymes), peptides, peptide mimetics, etc. In some embodiments, an agent is or comprises a polymer. In some embodiments, an agent is not a polymer and / or is substantially free of any polymer. In some embodiments, an agent contains at least one polymeric moiety. In some embodiments, an agent is free or substantially free of any polymeric moieties. Gets better-. As used herein, "improvement" refers to the prevention, reduction, and / or palliation of a condition, or improvement of the condition of a subject. Improvement includes, but does not require complete recovery from, or complete prevention of, a disease, disorder, or condition. amino acid As used herein, the term "amino acid" in its broadest sense refers to any compound and / or substance that can be incorporated into a polypeptide chain. In some embodiments, an amino acid has the general structure H 2 N-C(H)(R)-COOH. In some embodiments, an amino acid is a naturally occurring amino acid. In some embodiments, an amino acid is a synthetic amino acid; in some embodiments, an amino acid is a d-amino acid; in some embodiments, an amino acid is an I-amino acid. "Standard amino acid" refers to any of the twenty standard l-amino acids commonly found in naturally occurring peptides. "Non-standard amino acid" refers to any amino acid, other than the standard amino acids, regardless of whether it is synthetically prepared or obtained from a natural source. As used herein, "synthetic amino acid" encompasses chemically modified amino acids, including, but not limited to salts, amino acid derivatives (such as amides), and / or substitutions. Amino acids, including carboxy- and / or amino-terminal amino acids in peptides, they can be modified by mediation, amidation, acetylation, protecting groups and / or substitution with other chemical groups that can change the circulating half-life of the peptide without adversely affecting its activity. Amino acids can participate in a disulfide bond. Amino acids may comprise one or more post-translational modifications, such as association with one or more chemical entities (eg, methyl groups, acetate groups, acetyl groups, phosphate groups, formyl moieties, isoprenoid groups, sulfate groups, polyethylene glycol moieties , lipid residues, carbohydrate residues, biotin residues, efe?.). The term "amino acid" is used interchangeably with "amino acid residue", and may refer to a free amino acid and / or an amino acid residue of a peptide. It will be apparent from the context in which the term is used whether it refers to a free amino acid or a peptide residue. Antibody: As used herein, the term "antibody" refers to a polypeptide that includes elements of canonical immunoglobulin sequence sufficient to confer specific binding to a particular target antigen. As is known in the art, intact antibodies as they occur in nature are tetrameric agents of approximately 150 kD, consisting of two identical heavy chain polypeptides (approximately 50 kD each) and two identical light chain polypeptides (approximately 25 kD). kD each) that associate with each other, commonly referred to as a "Y-shaped" structure. Each of the heavy chains is composed of at least four domains (each about 110 amino acids in length)—an amino-terminal variable domain (VH) (located at the tips of the Y structure), followed by three constant domains. : CHI, CH2, and the carboxy-terminal CH3 (located at the base of the stem of the Y). A short region, known as the "switch," connects the heavy chain variable and constant regions. The "hinge" connects the CH2 and CH3 domains to the rest of the antibody. Two disulfide bonds in this hinge region connect the two heavy chain polypeptides to each other in an intact antibody. Each of the light chains comprises two domains - an amino-terminal variable domain (VL), followed by a carboxy-terminal constant domain (CL), separated from each other by another "switch". Intact antibody tetramers are composed of two heavy chain-light chain dimers, in which the heavy and light chains are linked together by a single disulfide bond; Two other disulfide bonds connect the heavy chain hinge regions to each other, so that the dimers are connected to each other and the tetramer is formed. Naturally produced antibodies are also glycosylated, typically in the CH2 domain. Each of the domains in a natural antibody has a structure characterized by an "immunoglobulin fold" formed from two beta sheets (eg, 3-, 4-, or 5-chain sheets) packed against each other in an antiparallel beta cylinder compressed. Each of the variable domains contains three hypervariable loops known as "complement determining regions" (CDR1, CDR2, and CDR3) and four somewhat invariant "framework" regions (FR1, FR2, FR3, and FR4). When natural antibodies fold, the FR regions form the beta sheets that provide the structural framework for the CDR domains and the CDR loop regions of the heavy and light chains come together in three-dimensional space so as to create a single binding site. hypervariable antigen located at the tip of the Y-structure. The Fc region of naturally occurring antibodies binds to elements of the complement system, and also to receptors on effector cells, including, for example, effector cells that mediate cytotoxicity. As is known in the art, the affinity and / or other binding attributes of Fe regions for Fe receptors can be modulated through glycosylation or other modification. In some embodiments, antibodies produced and / or used in accordance with the present disclosure include glycosylated Fc domains, including engineered or modified glycosylation Fc domains. For purposes of the present disclosure, in certain embodiments, any polypeptide or polypeptide complex that includes sufficient immunoglobulin domain sequences as found in natural antibodies may be referred to and / or used as an "antibody", whether said polypeptide is naturally occurring (eg, generated by an organism reacting to an antigen), or produced by recombinant engineering, chemical synthesis, or other artificial system or methodology. In some embodiments, an antibody is polyclonal; in some embodiments, an antibody is monoclonal. In some embodiments, an antibody has constant region sequences that are characteristic of mouse, rabbit, primate, or human antibodies. In some embodiments, the antibody sequence elements are fully human, or humanized, primatized, chimeric, etc. As known in the art. Furthermore, the term "antibody" as used herein may in appropriate embodiments refer (unless otherwise stated or clear from the context) any of the constructs or formats known in the art or developed for use structural and functional features of antibodies in alternative presentation. For example, in some embodiments, an antibody used in accordance with the present disclosure is in a format selected from, but not limited to, intact IgG, IgE, and IgM, b, or multi-specific antibodies (eg, Zybodies ®, etc.), Single Chain Fvs, Fc-Polypeptide Fusions, Fabs, Camidic Antibodies, Masked Antibodies (e.g. Probodies®), Small Modular ImmunoPharmaceuticals ("SMIPsTM"), Single or Tandem Chain dlabodies ( TandAb®), VHHs, Anticalins®, Nanobodies©, minibodies, B¡TE©s, ankyrin repeat proteins or DARPINs®, Avimers®, a DART, a TCR-like antibody, Adnectins®, Affilins®, Trans-bodies® , Affibodies®, a TrimerX®, MicroProteins, Fynomers®, Centyrins® and a KALBITOR®. In some embodiments, an antibody may lack a covalent modification (eg, glycan attachment) that could have been produced naturally. In some embodiments, an antibody may contain a covalent modification (eg, attachment of a glycan, payload (eg, detectable moiety, therapeutic moiety, catalytic moiety, etc.), or other pendant group (eg, poly- ethylene glycol, etc.)). Antibody-Dependent Cellular Cytotoxicity. As used herein, the term "antibody-dependent cellular cytotoxicity" or "ADCC" refers to a phenomenon in which antibody-bound target cells are killed by immune effector cells. Without wishing to be bound by any particular theory, ADCC is typically understood to imply that Fe receptor (FcR)-bearing effector cells can recognize and subsequently kill antibody-coated target cells (e.g., cells expressing envelope-specific antigens). surface to which an antibody binds). Effector cells that mediate ADCC can include immune cells, including but not limited to one or more of the natural killer (NK) cells, macrophages, neutrophils, eosinophils. Antibody Fragment-. As used herein, an "antibody fragment" includes a portion of an intact antibody, such as, for example, the variable or antigen-binding region of an antibody. Examples of antibody fragments include Fab, Fab', F(ab') fragments 2 and Fv; triabodies; tetrabodies; linear antibodies; single chain antibody molecules; and multi-specific antibodies formed from antibody fragments. For example, antibody fragments include isolated fragments, "Fv" fragments (consisting of the heavy and light chain variable regions), recombinant single chain polypeptide molecules, in which the heavy and light chain variable regions are connected by a peptide linker ("scFv proteins"), recombinant single domain antibodies consisting of an antibody heavy chain variable region (eg, VHH), and minimal recognition units consisting of the residues of amino acids that mimic a hypervariable region (eg, a hypervariable region of a heavy chain variable region (VH), a hypervariable region of a light chain variable region (VL), one or more CDR domains within the VH, and / or one or more CDR domains within the VL). In many embodiments, an antibody fragment contains a sufficient sequence of the parent antibody of which it is a fragment that binds the same antigen as the parent antibody; in some embodiments, a fragment binds antigen with an affinity comparable to that of the parent antibody and / or competes with the parent antibody for antigen binding. Examples of antigen-binding fragments of an antibody include, but are not limited to, Fab fragment, Fab' fragment, F(ab') fragment 2 , scFv fragment, Fv fragment, dsFv diabody, dAb fragment, Fd' fragment, Fd fragment, heavy chain variable region, and an isolated complementarity determining region (CDR). An antigen-binding fragment of an antibody can be produced by any means. For example, an antigen-binding fragment of an antibody can be produced enzymatically or chemically by fragmentation of an intact antibody and / or can be produced recombinantly. from a gene encoding the partial antibody sequence. Alternatively or additionally, the antigen-binding fragment of an antibody may be wholly or partially produced synthetically. An antigen binding fragment of an antibody may optionally comprise a single chain antibody fragment. Alternatively or additionally, an antigen-binding fragment of an antibody may comprise multiple chains that are linked together, for example by disulfide bonds. An antigen-binding fragment of an antibody may optionally comprise a multimolecular complex. A functional antibody fragment typically comprises at least about 50 amino acids, and more typically comprises at least about 200 amino acids. Antigen: The term "antigen" as used herein refers to an agent that elicits an immune response; and / or an agent that binds to a T cell receptor (eg, when presented by an MHC molecule) or to an antibody or antibody fragment. In some embodiments, an antigen elicits a humoral response (eg, including the production of antibodies specific for the antigen); in some embodiments, an antigen elicits a cellular response (eg, involving T cells whose receptors specifically interact with the antigen). In some embodiments, an antigen is bound by an antibody and may or may not induce a particular physiological response in an organism. In general, an antigen may be or include any chemical entity such as, for example, a small molecule, a nucleic acid, a polypeptide, a carbohydrate, a lipid, a polymer (in some embodiments other than a biological polymer (eg, eg, other than a nucleic acid or amino acid polymer)), etc. In some embodiments, an antigen is or comprises a polypeptide. In some embodiments, an antigen is or comprises a glycan. Those of ordinary skill in the art will appreciate that, in general, an antigen can be provided in isolated or pure form, or alternatively, it can be provided in crude form (eg, together with other materials, for example in an extract such as a cell extract or other relatively crude preparation from an antigen-containing source) or, alternatively, may exist on or in a cell. In some embodiments, an antigen is a recombinant antigen. antigen presenting cell 1 . The phrase "antigen-presenting cell" or "APC", as used herein, has the meaning understood in the art to refer to cells that process and present antigens to T cells. Illustrative APCs include dendritic cells, macrophages, B cells, certain activated epithelial cells, and other cell types capable of TCR stimulation and co-stimulation of appropriate T cells. About or about: As used herein, the term "about" or "about," as applied to one or more values ​​of interest, refers to a value that is similar to an established reference value. In certain embodiments, the term "about" or "approximately" refers to a range of values ​​that fall within 25%, 20%, 19%, 18%, 17%, 16%, 15%, 14%, 13%, 12%, 11 %, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1% or less in any direction (greater than or less than) of the established reference value, to unless otherwise stated or otherwise apparent from the context (except where such a number would exceed 100% of a possible value). Uniórr. It will be understood that the term "bond" as used herein typically refers to a non-covalent association between two or more entities. "Direct" bonding involves physical contact between entities or remains; Indirect union implies physical interaction by means of physical contact with one or more intermediate entities. Bonding between two or more entities can typically be assessed in any of a variety of contexts - including cases where interacting entities or moieties are studied in isolation or in the context of more complex systems (e.g., while are covalently or otherwise associated with a supporting entity and / or in a biological system or cell). Cancer. The terms "cancer", "malignant tumor", "neoplasm", "tumor" and "carcinoma" are used interchangeably herein to refer to cells that exhibit relatively abnormal, uncontrolled and / or autonomous growth, such that they exhibit an aberrant growth phenotype characterized by a significant loss of control of cell proliferation. In general, cells of interest for detection or treatment in the present application include precancerous (eg, benign), malignant, pre-metastatic, metastatic, and non-metastatic cells. The teachings of the present disclosure may be relevant to any and all cancers. To give a few non-limiting examples, in some embodiments, the teachings of the present disclosure apply to one or more cancers such as, for example, hematopoietic cancers including leukemias, lymphomas (Hodgkin's and non-Hodgkin's), myelomas, and disorders myeloproliferative; sarcomas, melanomas, adenomas, solid tissue carcinomas, squamous cell carcinomas of the mouth, throat, larynx, and lung, liver cancer, genitourinary cancers such as prostate, cervical, bladder, uterine, and endometrial cancer, and renal cell carcinomas , bone cancer, pancreatic cancer, skin cancer, cutaneous or intraocular melanoma, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancers of the head and neck, breast cancer, gastrointestinal cancers and cancers of the system nerve, benign lesions such as papillomas, and the like. Chimeric Antigen Receptor: "Chimeric Antigen Receptor" or "CAR" or "CARs", as used herein, refers to genetically engineered receptors, which engraft antigen specificity onto cells (eg, T cells). such as untreated T cells), central memory T cells, effector memory T cells or combination thereof). CARs are also known as artificial T cell receptors, T cell receptors chimeric or chimeric immunoreceptors. In some embodiments, the CARs comprise antigen-specific target regions, an extracellular domain, a transmembrane domain, one or more costimulatory domains, and an intracellular signaling domain. Combination Therapy: As used herein, the term "combination therapy" refers to those situations in which a subject is simultaneously exposed to two or more therapeutic regimens (eg, two or more therapeutic agents) . In some embodiments, two or more agents can be administered simultaneously; in some embodiments, said agents may be administered sequentially; in some embodiments, such agents are administered in overlapping dosage regimens. Dominic. The term "domain" is used herein to refer to a section or part of an entity. In some embodiments, a "domain" is associated with a particular structural and / or functional trait of the entity such that, when the domain is physically separated from the rest of its parent entity, it substantially or fully retains the structural and / or functional trait. particular. Alternatively or additionally, a domain may be or include a portion of an entity that, when separated from that entity (precursor) and linked to a different entity (recipient), substantially retains in and / or imparts to the recipient entity one or more more structural and / or functional features that characterize it in the precursor entity. In some embodiments, a domain is a section or part of a molecule (eg, a small molecule, carbohydrate, lipid, nucleic acid, or polypeptide). In some embodiments, a domain is a section of a polypeptide; in some of these embodiments, a domain is characterized by a particular structural element (eg, a particular amino acid sequence or sequence motif, an a-helix character, P-sheet character, coiled-coil character, random coil, etc.) and / or by a particular functional trait (eg, binding activity, enzyme activity, folding activity, signaling activity, etc.). Dosage Form: As used herein, the terms "dosage form" and "dosage unit form" refer to a physically discrete unit of a therapeutic agent for the patient to be treated. Each of the units contains a predetermined amount of active material calculated to produce the desired therapeutic effect. It will be understood, however, that the total dosage of the composition will be decided by the attending physician within the scope of reasonable medical judgment. Dosage Regimen: As used herein, the term "dosage regimen" refers to a set of unit doses (typically more than one) that are individually administered to a subject, typically separated by periods of time. In some embodiments, a given therapeutic agent has a recommended dosage regimen that may involve one or more doses. In some embodiments, a dosage regimen comprises a plurality of doses, each of which are separated from each other by an equal length of time; in some embodiments, a dosage regimen comprises a plurality of doses and at least two different time periods separating the individual doses. In some embodiments, all doses within a dosage regimen are of the same unit dose amount. In some embodiments, different doses within a dosage regimen are of different amounts. In some embodiments, a dosage regimen comprises a first dose in a first dose amount, followed by one or more additional doses in a second dose amount different from the first dose amount. In some embodiments, a dosage regimen comprises a first dose in a first dosage amount, followed by one or more additional doses in a second dosage amount equal to the first dosage amount. In some embodiments, a dosage regimen correlates with a desired or beneficial outcome when administered across a relevant population (ie, it is a therapeutic dosage regimen). Effector Function- As used herein, "effector function" refers to a biochemical event that results from the interaction of an Fc region of antibody with an Fc receptor or ligand. Effector functions include, but are not limited to antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), and complement-mediated cytotoxicity (CMC). In some embodiments, an effector function is one that operates following antigen binding, one that operates independently of antigen binding, or both. Effector Cell - As used herein, "effector cell" refers to a cell of the immune system that expresses one or more Fe receptors and mediates one or more effector functions. In some embodiments, effector cells may include, but are not limited to one or more of monocytes, macrophages, neutrophils, dendritic cells, eosinophils, mast cells, platelets, large granular lymphocytes, Langerhans cells, Natural Killer (NK) cells, Lymphocytes. T B lymphocytes and can be from any organism including but not limited to humans, mice, rats, rabbits and monkeys. Expression- As used herein, "expression" of a nucleic acid sequence refers to one or more of the following events: (1) production of an RNA template from a DNA sequence (eg. g., by transcription); (2) processing of an RNA transcript {p. eg, by splicing, editing, 5' capping and / or 3' capping; (3) translation of an RNA into a polypeptide or protein; and / or (4) post-translational modification of a polypeptide or protein. extracellular domain. As used herein, "extracellular domain" (or "ECD") refers to a portion of a polypeptide that extends beyond the domain of transmembrane in the extracellular space. Fusion protein-. As used herein, the term "fusion protein" generally refers to a polypeptide that includes at least two segments, each of which exhibits a high degree of amino acid identity to a peptide moiety that ( 1) occurs in nature and / or (2) represents a functional domain of a polypeptide. Typically, a polypeptide containing at least two such segments is considered to be a fusion protein if the two segments are residues that (1) are not naturally included in the same peptide and / or (2) have not been linked. previously linked to each other into a single polypeptide and / or (3) have been linked to each other through the action of man. Gen-, As used herein, the term "gene" has its meaning as understood in the art. Those of ordinary skill in the art will appreciate that the term "gene" may include gene regulatory sequences {eg. g., promoters, enhancers, etc.) and / or intron sequences. It will further be appreciated that the definitions of gene include references to nucleic acids that do not encode proteins, but encode functional RNA molecules such as tRNAs, RNAi-inducing agents, etc. For purposes of clarity, it will be noted that, as used in the present application, the term "gene" generally refers to a portion of a nucleic acid that encodes a protein; the term may optionally encompass regulatory sequences, as will be clear from the context to those of ordinary skill in the art. This definition is not intended to exclude the application of the term "gene" to non-protein expression units, but rather to clarify the same, in most cases, the term, as used in this document, refers to an acid protein-coding nucleic. Gene product or expression product-. As used herein, the term "gene product" or "expression product" generally refers to an RNA transcribed from the gene (pre- and / or post-processing) or a polypeptide (pre- and / or post-modification) encoded by an RNA transcribed from the gene. Immune Response: As used herein, the term "immune response" refers to a response elicited in an animal. An immune response may refer to cellular immunity, humoral immunity, or may involve both. An immune response can also be limited to one part of the immune system. For example, in certain embodiments, an immunogenic composition can induce an increased IFNγ response. In certain embodiments, an immunogenic composition can induce a mucosal IgA response (eg, as measured in nasal and / or rectal washes). In certain embodiments, an immunogenic composition can induce a systemic IgG response (eg, as measured in serum). In certain embodiments, an immunogenic composition can induce virus neutralizing antibodies or a neutralizing antibody response. In certain embodiments, a Immunogenic composition can induce a cytolytic response (CTL) by T cells. Improve, increase or reduce. As used herein, the terms "improve", "increase" or "reduce" or grammatical equivalents, indicate values ​​that are relative to a baseline measurement, such as a measurement in the same individual before the start of treatment. treatment described herein, or a measurement in a control individual (or multiple control individuals) in the absence of the treatment described herein. Individual, subject, patient. As used herein, the terms "subject", "individual" or "patient" refer to a human or non-human mammalian subject. The individual (also referred to as "patient" or "subject") is an individual (fetus, infant, child, adolescent, or adult) suffering from a disease, eg, cancer. In some embodiments, the subject is a human. Linker: As used herein, the term "linker" refers to, e.g. g., in a fusion protein, to an amino acid sequence of an appropriate length other than that which occurs at a particular position in the native protein and is generally designed to be flexible and / or to interpose a structure, such as a helix a, between two protein moieties. In general, a linker allows two or more domains of a fusion protein to retain 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or more of the biological activity of each of the domains. A linker can also be referred to as a spacer. Rest of masking? As used herein, "masking moiety" refers to a molecular moiety that, when bound to an antigen-binding protein described herein, is capable of masking the binding of said antigen-binding moiety to its target antigen. An antigen-binding protein comprising such a masking moiety is referred to herein as a "masked" antigen-binding protein. Nucleic Acid As used herein, "nucleic acid", in its broadest sense, refers to any compound and / or substance that can be incorporated into a chain of oligonucleotides. In some embodiments, a nucleic acid is a compound and / or substance that is or can be incorporated into an oligonucleotide chain via a phosphodiester bond. As will be clear from the context, in some embodiments, "nucleic acid" refers to individual nucleic acid residues (eg, nucleotides and / or nucleosides); in some embodiments, "nucleic acid" refers to an oligonucleotide chain comprising individual nucleic acid residues. In some embodiments, a "nucleic acid" is or comprises RNA; in some embodiments, a "nucleic acid" is or comprises DNA. In some embodiments, an acid is, comprises, or consists of one or more naturally occurring nucleic acid residues. In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleic acid analogs. In some embodiments, a nucleic acid analog differs from a nucleic acid in that it does not use a phosphodiester backbone. For example, in some embodiments, a nucleic acid is, comprises, or consists of one or more "peptide nucleic acids", which are known in the art and have peptide bonds rather than phosphodiester bonds in the backbone, are considered within the scope of the present invention. Alternatively or additionally, in some embodiments, a nucleic acid has one or more phosphorothioate and / or 5'-N-phosphoramidite linkages in place of phosphodiester linkages. In some embodiments, a nucleic acid is, comprises, or consists of one or more naturally occurring nucleosides (eg, adenosine, thymidine, guanosine, cytidine, uridine, deoxyadenosine, deoxythymidine, deoxy-guanosine, and deoxycytidine). In some embodiments, a nucleic acid is, comprises, or consists of one or more nucleoside analogs (eg, 2-aminoadenosine, 2-thiothymidine, inosine, pyrrolo-pyrimidine, 3-methyl-adenosine, 5-methylcytidine, C -5-propynyl-cytidine, C-5-propynyl-uridine, 2-aminoadenosine, C5-bromouridine, C5-fluorouridine, C5-iodouridine, C5-propynyl-uridine, C5-propynyl-cytidine, C5-methylcyt¡d [alpha], 2-aminoadenosine, 7-deaza-adenosine, 7-deazaguosine, 8-oxoadenosine, 8-oxoguanosine, 0(6)-methylguanine, 2-thiocytidine, mediated bases, intercalated bases, and combinations thereof). In some embodiments, a nucleic acid comprises one or more modified sugars (eg, 2'-fluororibose, ribose, 2'-deoxyribose, arabinose, and hexose) compared to those of natural nucleic acids. In some embodiments, a nucleic acid has a nucleotide sequence that encodes a functional gene product such as an RNA or protein. In some embodiments, a nucleic acid includes one or more introns. In some embodiments, the nucleic acids are prepared by one or more of isolation from a natural source, enzymatic synthesis by complementary template-based polymerization (in vivo or in vitro), reproduction in a cell or recombinant system, and chemical synthesis. In some embodiments, a nucleic acid is at least 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 , 75, 80, 85, 90, 95, 100, 1 10, 120, 130, 140, 150, 160, 170, 180, 190, 20, 225, 250, 275, 300, 325, 350, 375, 400, 425, 450, 475, 500, 600, 700, 800, 900, 1000, 1500, 2000, 2500, 3000, 3500, 4000, 4500, 5000 or more residues in length. In some embodiments, a nucleic acid is single-stranded; in some embodiments, a nucleic acid is double-stranded. In some embodiments, a nucleic acid has a nucleotide sequence that comprises at least one coding element, or is the complement of a polypeptide-encoding sequence. In some embodiments, a nucleic acid has enzymatic activity. Operationally linked. As used herein, "operatively linked" refers to a juxtaposition, where the components described are in a relationship that allows them to function in the manner intended. A control sequence "operably linked" to one or more coding sequences is linked in such a way that expression of one or more coding sequences is achieved under conditions compatible with the coding sequences. control. "Operably linked" sequences include both expression control sequences that are contiguous with the gene(s) of interest and expression control sequences that act in trans or at a distance to control the gene(s) of interest. The term "expression control sequence" as used herein refers to polynucleotide sequences that are necessary to effect expression and processing of the coding sequences to which they are linked. Expression control sequences include appropriate transcription initiation, termination, promoter, and enhancer sequences; efficient RNA processing signals such as splicing and polyadenylation signals; sequences that stabilize cytoplasmic mRNA; sequences that enhance translation efficiency (ie, the Kozak consensus sequence); sequences that enhance protein stability; and when desired, sequences that enhance protein secretion. The nature of such control sequences differs depending on the host organism. For example, in prokaryotes, control sequences generally include the promoter, ribosomal binding site, and transcription termination sequence, whereas in eukaryotes, these control sequences typically include promoters and transcription termination sequence. The term "control sequences" is intended to include components whose presence is essential for their expression and processing, and may also include additional components whose presence is advantageous, for example, leader sequences and fusion participant sequences. Patient. As used herein, the term "patient" refers to any organism to which a provided composition is or may be administered, e.g. eg, for experimental, diagnostic, prophylactic, cosmetic and / or therapeutic purposes. Typical patients include animals (eg, mammals such as mice, rats, rabbits, non-human primates, and / or humans). In some embodiments, a patient is a human. In some embodiments, a patient suffers from or is susceptible to one or more disorders or conditions. In some embodiments, a patient exhibits one or more symptoms of a disorder or condition. In some embodiments, a patient has been diagnosed with one or more disorders or conditions. In some embodiments, the disorder or condition is or includes cancer, or the presence of one or more tumors. In some embodiments, the patient is receiving or has received a certain therapy to diagnose and / or treat a disease, disorder, or condition. peptide. The term "peptide" as used herein refers to a polypeptide that is typically relatively short, for example, less than about 100 amino acids in length, less than about 50 amino acids, less than 20 amino acids, or less. of 10 amino acids. Pharmaceutically acceptable. The term "pharmaceutically acceptable" as used herein refers to substances which, within the scope of a criterion medically reasonable, are suitable for use in contact with human and animal tissue without undue toxicity, irritation, allergic response, or other problem or complication, based on a reasonable benefit / risk ratio. Polypeptide As used herein, a "polypeptide", in general terms, is a chain of at least two amino acids linked together by a peptide bond. In some embodiments, a polypeptide can include at least 3-5 amino acids, each of which is linked to one another via at least one peptide bond. Those of ordinary skill in the art will appreciate that polypeptides sometimes include "non-natural" amino acids or other entities that are nonetheless capable of being integrated into a polypeptide chain, optionally. Promoter. As used herein, a "promoter" is a DNA sequence recognized by the cell's synthetic machinery, or introduced synthetic machinery, required to initiate specific transcription of a polynucleotide sequence. A "constitutive" promoter is a nucleotide sequence that, when operably linked to a polynucleotide that encodes or specifies a gene product, causes the gene product to be produced in a cell under most or all physiological conditions of the cell. An "inducible" promoter is a nucleotide sequence that, when operably linked to a polynucleotide that encodes or specifies a gene product, causes the gene product to be produced in a cell substantially only when an inducer specific for the promoter is present in the cell. cell. Protein: As used herein, the term "protein" refers to a polypeptide (ie, a chain of at least two amino acids linked together by peptide bonds). The proteins may include residues other than amino acids (eg, they may be glycoproteins, proteoglycans, etc.) and / or may be processed or otherwise modified. Those of ordinary skill in the art will appreciate that a "protein" may be an entire polypeptide chain as produced by a cell (with or without a signal sequence) or may be a part thereof. Those of ordinary skill in the art will appreciate that a protein can sometimes include more than one polypeptide chain, eg, linked by one or more disulfide bonds or associated by other means. The polypeptides may contain L-amino acids, D-amino acids, or both, and may contain any of a variety of amino acid modifications or analogs known in the art. Useful modifications include, e.g. g., terminal acetylation, amidation, methylation, etc. In some embodiments, the proteins may comprise natural amino acids, unnatural amino acids, synthetic amino acids, and combinations thereof. Reference?. As used herein, "reference" describes a standard or control against which a comparison is made. For example, in some embodiments, an agent, animal, individual, population, sample, sequence, or value of interest is compared to a agent, animal, individual, population, sample, sequence, or reference or control value. In some embodiments, a reference or control is tested and / or determined substantially simultaneously with the test or determination of interest. In some embodiments, a reference or control is a historical reference or control, optionally embodied in a tangible medium. Typically, as will be understood by those skilled in the art, a reference or control is determined or characterized under conditions or circumstances comparable to those under evaluation. Those skilled in the art will appreciate when sufficient similarities are present to justify reliance on and / or comparison with a particular possible reference or control. Solid tumor-. As used herein, the term "solid tumor" refers to an abnormal mass of tissue that does not normally contain cysts or fluid areas. Solid tumors can be benign or malignant. Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, lymphomas, mesothelioma, neuroblastoma, retinoblastoma, etc. Cancer phase. As used herein, the term "cancer stage" refers to a qualitative or quantitative assessment of the level of progression of a cancer. Criteria used to determine the stage of a cancer include, but are not limited to, the size of the tumor and the degree of metastasis (eg, localized or distant). Subject-.. By "subject" is meant a mammal (eg, a human, in some embodiments including prenatal human forms). In some embodiments, a subject is suffering from a relevant disease, disorder, or condition. In some embodiments, a subject is susceptible to a disease, disorder, or condition. In some embodiments, a subject exhibits one or more symptoms or characteristics of a disorder, disease, or condition. In some embodiments, a subject does not exhibit any symptoms or characteristics of a disease, disorder, or condition. In some embodiments, a subject is someone with one or more traits characteristic of susceptibility to or risk of a disease, disorder, or condition. In some embodiments, a subject is a patient. In some embodiments, a subject is an individual to whom the diagnosis and / or therapy is and / or has been administered. Suffers from?. An individual who "suffers" from a disease, disorder, or condition {p. g., cancer) has been diagnosed with and / or exhibits one or more symptoms of the disease, disorder, or condition. Symptoms are reduced: In accordance with the present invention, "symptoms are reduced" when one or more symptoms of a particular disease, disorder or condition are reduced in magnitude {eg. g., intensity, severity, etc.} or frequency. For purposes of clarity, a delay in the onset of a particular symptom is considered a way to reduce the frequency of that symptom. It is not intended that the present invention be limited solely to cases where the symptom. The present invention specifically contemplates treatment such that one or more symptoms are reduced (and the subject's condition is thereby "improved"), but not completely eliminated. T Cell Receptor As used herein, a "T cell receptor" or "TCR" refers to antigen recognition molecules present on the surface of T cells. During normal T cell development, each Of the four TCR genes, o, p, and y o, can rearrange, leading to highly diverse TCR proteins. therapeutic agent. As used herein, the phrase "therapeutic agent" generally refers to any agent that produces a desired pharmacological effect when administered to an organism. In some embodiments, an agent is considered to be a therapeutic agent if it demonstrates a statistically significant effect across an appropriate population. In some embodiments, the appropriate population may be a population of model organisms. In some embodiments, an appropriate population may be defined by various criteria such as a certain age group, gender, genetic background, pre-existing clinical conditions, etc. In some embodiments, a therapeutic agent is a substance that can be used to alleviate, ameliorate, inhibit, prevent, delay the onset, reduce the severity, and / or reduce the incidence of one or more symptoms or features of a disease, disorder, and / or disease. or condition. In some embodiments, a "therapeutic agent" is an agent that has been or is required to be approved by a government agency before it can be marketed for administration to humans. In some embodiments, a "therapeutic agent" is an agent for which a medical prescription is required for administration to humans. Therapeutically Effective Amount: As used herein, the term "therapeutically effective amount" means an amount that is sufficient, when administered to a population suffering from or susceptible to a disease, disorder and / or condition in accordance with a therapeutic dosage regimen, to treat the disease, disorder and / or condition. In some embodiments, a therapeutically effective amount is one that reduces the incidence and / or severity of, stabilizes one or more features of, and / or delays the onset of one or more symptoms of the disease, disorder, and / or condition. Those skilled in the art will appreciate that the term "therapeutically effective amount" does not in fact require successful treatment to be achieved in a particular individual. Rather, a therapeutically effective amount may be that amount which provides a particular desired pharmacological response in a significant number of subjects when administered to patients in need of such treatment. For example, in some embodiments, "therapeutically effective amount" refers to an amount that, when administered to an individual in need thereof in the context of the therapy of the invention, will block, stabilize, attenuate, or reverse a process of support of cancer that occurs in said individual, or will potentiate or increase a cancer suppressive process in said individual. In the context of cancer treatment, a "therapeutically effective amount" is an amount that, when administered to an individual diagnosed with cancer, will prevent, stabilize, inhibit, or reduce further development of cancer in the individual. A particularly preferred "therapeutically effective amount" of a composition described herein reverses (in a therapeutic treatment) the growth of a malignant tumor such as pancreatic carcinoma, or helps to achieve or prolong remission of a malignant tumor. A therapeutically effective amount administered to an individual to treat a cancer in which the individual may be the same as or different from a therapeutically effective amount to promote remission or inhibit metastasis. As with most cancer therapies, the therapeutic methods described herein should not be construed as, restricted to, or otherwise limited to a "cure" for cancer; rather, the methods of treatment are directed to the use of the disclosed compositions to "treat" a cancer, that is, to effect a desirable or beneficial change in the health of an individual having cancer. Such benefits are recognized by health care providers skilled in the field of oncology and include, but are not limited to, a stabilization of the patient's condition, a decrease in tumor size (tumor regression), an improvement in vital functions (eg, improved function of cancerous tissues or organs), a decrease or inhibition of further metastasis, a decrease in opportunistic infections, increased survival, a decrease in pain, improved motor function, cognitive function improved, an improved sense of energy (vitality, decreased malaise), improved sense of well-being, restoration of normal appetite, restoration of healthy weight gain, and combinations thereof. In addition, the regression of a particular tumor in an individual (eg, as a result of the treatments described herein) can also be assessed by sampling cancer cells from the site of a tumor such as a pancreatic adenocarcinoma (eg, during the course of treatment) and assaying the cancer cells for the level of metabolic and signaling markers to monitor the status of the cancer cells to verify at the molecular level the regression of the cancer cells to a less malignant phenotype. For example, tumor regression induced using the methods of this invention would be indicated by finding a decrease in one or more pro-angiogenic markers, an increase in anti-angiogenic markers, normalization (i.e., alteration toward a state found in normal individuals who do not have cancer) of metabolic pathways, intercellular signaling pathways, or intracellular signaling pathways that exhibit abnormal activity in individuals diagnosed with cancer. Those of ordinary skill in the art will appreciate that, in some embodiments, a therapeutically effective amount may be formulated and / or administered in a single dose. In some embodiments, a therapeutically effective amount can be formulated and / or administered in a plurality of doses, eg, as part of a dosage regimen. Transformation: As used herein, "transformation" refers to any process by which exogenous DNA is introduced into a host cell. The transformation can occur under natural or artificial conditions using various methods well known in the art. Transformation can be based on any known method for inserting foreign nucleic acid sequences into a prokaryotic or eukaryotic host cell. In some embodiments, a particular transformation methodology is selected based on the host cell to be transformed and may include, but is not limited to viral infection, electroporation, mating, lipofection. In some embodiments, a "transformed" cell is stably transformed, in which the inserted DNA is capable of replicating either as an autonomously replicating plasmid or as part of the host chromosome. In some embodiments, a transformed cell transiently expresses introduced nucleic acid for limited periods of time. Treatment: As used herein, the term "treatment" (also "treating" or "treating") refers to any administration of a substance that partially or completely relieves, ameliorates, relieves, inhibits, delays the onset, reduces the severity and / or reduce the incidence of one or more symptoms, traits, and / or causes of a particular disease, disorder, and / or condition (eg, cancer). Said treatment may be of a subject exhibiting no signs of the relevant disease, disorder and / or condition and / or of a subject exhibiting only early signs of the disease, disorder and / or condition. Alternatively or additionally, such treatment may be of a subject exhibiting one or more established signs of the relevant disease, disorder and / or condition. In some embodiments, the treatment may be of a subject diagnosed as having the relevant disease, disorder and / or condition. In some embodiments, the treatment may be of a subject known to have one or more susceptibility factors that statistically correlate with increased risk of developing the relevant disease, disorder and / or condition. Tumor Infiltrating Lymphocyte As used herein, the term "tumor infiltrating lymphocytes" refers to white blood cells from a subject suffering from cancer (such as melanoma), which have left the bloodstream and migrated to a. tumor. In some embodiments, the tumor infiltrating lymphocytes are tumor specific. Vector. As used herein, "vector" refers to a nucleic acid molecule capable of transporting another nucleic acid with which it is associated. In some embodiments, the vectors are capable of extra-chromosomal replication and / or expression of nucleic acids to which they are linked in a host cell such as a eukaryotic and / or prokaryotic cell. Vectors capable of directing the expression of operatively linked genes have been referred to herein as "expression vectors". DETAILED DESCRIPTION OF THE INVENTION Among other things, the present invention provides methods and compositions useful for the treatment of cancer. Specifically, the present disclosure provides cellular therapeutics, e.g. g., immune cells, genetically modified with an integrated gene, e.g. eg, a nucleotide sequence of interest (eg, a constitutive expression construct and / or an inducible expression construct including said nucleotide sequence). In some embodiments, expression of a nucleotide sequence of interest can be designed to be constitutive or inducible by appropriate selection, construction, and / or design of an expressed promoter sequence operably linked to said nucleotide sequence of interest, as described in this memory. In the case of a constitutive expression construct, a gene in the construct is constitutively expressed. In the case of an inducible expression construct, a cellular therapeutic agent may be engineered with a nucleic acid encoding an antigen-binding receptor and an inducible expression construct. Upon binding of a target antigen, an antigen-binding receptor for a cellular therapeutic agent induces expression of a gene included in an inducible expression construct, e.g. eg, as depicted in Figure 1. In certain embodiments, expression of such a gene facilitates and / or improves cancer treatment, e.g. eg, by one or more cell therapies. The invention also specifically describes protein therapeutic agents including proteins encoded by these genes (eg, soluble forms of such gene products, eg, pharmaceutical compositions including such proteins for administration), and nucleic acids encoding such proteins, such as for gene therapy. Constitutive Expression Constructions In some embodiments, the disclosure includes constitutive expression constructs. In some embodiments, a constitutive expression construct comprises a nucleic acid sequence that includes at least one promoter operably linked to a nucleotide sequence of interest, e.g. eg, a gene described herein. A constitutive expression construct may comprise regulatory sequences such as transcriptional and translational initiation and termination codons. In some embodiments, such regulatory sequences are specific to the cell type into which the non-inducible expression construct is to be introduced, as appropriate. A constitutive expression construct may comprise a native or non-native promoter operably linked to a sequence of nucleotides of interest. Preferably, the promoter is functional in immune cells. Illustrative promoters include, e.g. eg, the CMV promoter, E1F, VAV, TCRvbeta, MCSV, and PGK. Operable linkage of a nucleotide sequence to a promoter is within the skill of the skilled person. In some embodiments, a constitutive expression construct is or includes a recombinant expression vector described herein. Inducible Expression Constructs v Inducible Expression For inducible expression, a cellular therapeutic agent of the present disclosure may include (i) one or more types of antigen-binding receptors comprising an extracellular domain, a transmembrane domain, and an intracellular (or cytoplasmic) domain, and (! i) an inducible expression construct. Antigen Binding Receptors The extracellular domain of an antigen-binding receptor comprises a target-specific antigen-binding domain. The intracellular domain (or cytoplasmic domain) of an antigen-binding receptor comprises a signaling domain. The signaling domain includes an amino acid sequence that, upon binding of the target antigen to the antigen-binding domain, initiates and / or mediates an intracellular signaling pathway that can activate, among other things, an inducible expression construct described in this memory, so that an inducible gene is expressed. In some embodiments, a signaling domain further includes one or more additional signaling regions (eg, costimulatory signaling regions) that activate one or more effector functions of immune cells (eg, effector functions). of native immune cells). In some embodiments, the signaling domain activates T cell activation, proliferation, survival, or other T cell function, but does not induce cytotoxic activity. In some embodiments, an antigen binding receptor includes all or part of a chimeric antigen receptor (CAR). Such CARs are known in the art (see, e.g., Gill et al., Immunol. Rev. 263:68-89 (2015); Stauss et al., Curr. Opin. Pharmacol. 24:113-118 (2015)). Antigen Binding Domain An antigen binding domain may be or include any polypeptide that specifically binds a target antigen, e.g. eg, a tumor antigen described herein. For example, in some embodiments, an antigen-binding domain includes an antibody or antigen-binding fragment described herein (eg, Fab fragment, Fab' fragment, F(ab') fragment). 2 / scFv fragment, Fv fragment, dsFv diabody, dAb fragment, Fd' fragment, Fd fragment, an isolated complementarity determining region (CDR), an antibody camelid, a masked antibody (eg, Probody©), a single chain or Tandem diabody (TandAb®), a VHH, an Anticalin®, a single domain antibody (eg, Nanobody®) , an ankyrin repeat protein or DARNIP®, an Avimer®, an Adnectin®, an Affilin®, an Afliger®, a Fynmer®, or a Centyrin®). In some embodiments, an antigen-binding domain is or includes a T cell receptor (TCR) or an antigen-binding portion thereof. In some embodiments, an antigen-binding domain is a pH-sensitive domain (see, eg, Schroter et al. MAbs 7: 138-51 (2015)). Antigen-binding domains can be selected based on, e.g. eg, the type and number of target antigens present on or near a surface of a target cell. For example, an antigen binding domain may be chosen to recognize an antigen that acts as a cell surface marker on a target cell associated with a particular disease state. In some embodiments, an antigen binding domain is selected to specifically bind an antigen on a tumor cell. Tumor antigens are proteins that are produced by tumor cells and, in some embodiments, that elicit an immune response, particularly T cell-mediated immune responses. Selection of an antigen-binding domain may depend, e.g. eg, of a particular type of cancer to be treated. Transmembrane domain In general, a "transmembrane domain," as used herein, refers to a domain that has an attribute of being membrane-present (eg, spanning a portion or all of a cell membrane). As will be appreciated, not every amino acid in a transmembrane domain is required to be present in the membrane. For example, in some embodiments, a transmembrane domain is characterized in that a designated stretch or portion of a protein is substantially membrane localized. As is well known in the art, nucleic acid or amino acid sequences can be analyzed using a variety of algorithms to predict protein subcellular localization (eg, transmembrane localization). Illustrative programs of this type include psort (PSORT.g), Prosite (prosite.expasy.org), among others. The type of transmembrane domain included in an antigen-binding receptor described herein is not limited to any particular type. In some embodiments, a transmembrane domain is selected that naturally associates with an antigen-binding domain and / or intracellular domain. In some cases, a transmembrane domain includes a modification of one or more amino acids (eg, deletion, insertion, and / or substitution), e.g. eg, to prevent binding of said domains to a transmembrane domain of the same or different surface membrane proteins to minimize interactions with other members of the receptor complex. A transmembrane domain can be derived from a natural or synthetic source. In cases where the source is natural, a domain can be derived from any membrane-bound or transmembrane protein. Illustrative transmembrane regions may be derived from (eg, may comprise at least one transmembrane region(s) from) an alpha, beta, or zeta chain of a T-cell receptor, CD28, CD3 epsilon, CD45, CD4, CD5, CD8 , CD9, CD16, CD22, CD27, CD33, CD37, CD64, CD80, CD86, CD134, CD137, TNFSFR25, or CD154. Alternatively, a transmembrane domain may be synthetic (and may comprise, eg, predominantly hydrophobic residues such as leucine and valine). In some embodiments, a triplet of phenylalanine, tryptophan, and valine is included at each end of a synthetic transmembrane domain. In some embodiments, a transmembrane domain is directly linked to a cytoplasmic domain. In some embodiments, a short polypeptide or oligopeptide linker (eg, between 2 and 10 amino acids in length) can form a link between a transmembrane domain and an intracellular domain. In some embodiments, a linker is a glycine-serine doublet. Cytoplasmic Domain The intracellular domain (or cytoplasmic domain) comprises a signaling domain that, upon binding of the target antigen to the antigen-binding domain, initiates and / or mediates an intracellular signaling pathway that induces the expression of an inducible expression construct described in this memory. Intracellular signaling domains that can transduce a signal upon binding of an antigen to an immune cell are known, any of which can be used herein. For example, cytoplasmic sequences of a T cell receptor (TCR) are known to initiate signal transduction after binding of the TCR to an antigen (see, eg, Brownlie et al., Nature Rev. Immunol. 13:257-269 (2013)). In some embodiments, a signaling domain includes an immunoreceptor tyrosine-based activation motif (ITAM). Examples of ITAM-containing cytoplasmic signaling sequences include those derived from TCR Zeta, FcR gamma, FcR beta, CD3 zeta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d (see, eg, Love et al., Cold Spring Harb. Perspect. Biol. 2:a002485 (2010); Smith-Garvin et al., Annu. Rev. Immunol. 27:591-619 (2009)). In some embodiments, an intracellular signaling domain does not include a sequence that transduces a signal leading to death by T cells (eg, CD8 T cells). + ). For example, TCR cytoplasmic sequences are known to activate a number of signaling pathways, some of which lead to extermination (see, eg, Smith-Garvin et al., Annu. Rev. Immunol. 27:591 -619 (2009)). In some embodiments, an intracellular domain includes a signaling domain leading to signal transduction that mediates expression of an inducible expression construct, but without induction of killing (eg, as exemplified in Figure 6). For example, the cytoplasmic domain may include a cytoplasmic portion of a PDGF receptor and, upon antigen binding by the antigen-binding domain, may drive an intracellular signal that induces an inducible expression construct promoter. One of skill in the art, based on knowledge of the art, can select an intracellular domain and a related promoter to be included within an inducible expression construct. It is known that signals generated through a TCR alone are insufficient for full activation of a T cell and that a secondary or costimulatory signal is also required. Thus, in some embodiments, a signaling domain further includes one or more additional signaling regions (eg, co-stimulatory signaling regions) that activate one or more effector functions of immune cells (eg, ., an effector function of native immune cells described herein). In some embodiments, a portion of such co-stimulatory signaling regions may be used, as long as the portion transduces the effector function signal. In some embodiments, a cytoplasmic domain described herein includes one or more cytoplasmic sequences of a T cell coreceptor (or fragment thereof). Non-limiting examples of such T cell co-receptors include CD27, CD28, 4-1BB (CD137), 0X40, CD30, CD40, PD-1, ICOS, lymphocyte function associated antigen-1 (LFA-1 ), MYD88, CD2, CD7, LIGHT, NKG2C, B7-H3, and a ligand that specifically binds CD83. In some embodiments, two or more signaling domains are linked to each other in a random or specified order. Optionally, a short polypeptide or oligopeptide linker (eg, between 2 and 10 amino acids in length) can form the linkage. In some embodiments, such a linker is a glycine-serine doublet. Illustrative Antigen-Binding Receptors In some embodiments, a transmembrane and / or cytoplasmic domain is derived from a receptor tyrosine kinase (RTK). RTKs are a large and diverse family of cell surface receptors that transmit signals that trigger various physiological responses depending on cell type and cell surface signal integration. Many RTKs are suitable for transmitting signals in T cells, as the downstream components for signaling widely shared across cell types (Schlessinger, J. 2000. Cell Signaling by Receptor Review Tyrosine Kinases Cell 103, 211-225). The example given below is directed at PDGF receptors. These receptors are illustrative, and other pairs of receptors, e.g. eg, SCF-R and c-kit, and other heterodimeric and homodimeric receptors. RTKs are divided into subfamilies based on the way the receptors signal in response to ligand binding. An example is the PDGFR family (type III RTKs) which contains the two PDGF receptors (PDGFR-alpha (a) and PDGFR-beta (0)), CSF1R, KIT, RK2 and FLT3. These receptors signal upon dimerization which is induced by ligand binding - the ligands being members of the PDGF family. Receptors can signal as homodimers (aa and 00) and as the heterodimer (a0) (Wu e, Palmer N, Tian Z, Moseman AP, Galdzicki M, et al. (2008) Comprehensive Dissection of PDGF-PDGFR Signaling Pathways in PDGFR Genetically Defined Cells.PLoS ONE 3:e3794.doi:10.1371 / journal.pone.0003794). PDGFRs and several other TYPE III RTKs are deregulated in some T-cell malignancies, and other hematologic malignancies, illustrating their potential for signal proliferation and survival without triggering cytotoxic activity (Wadleigh M, DeAngelo DJ, Griffin JD, Stone RM 2005 After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies Blood 105 22-30 Blood 2010 Jan 7 115(1) 51-60 Yang J et al Platelet -derived growth factor mediates survival of leukemic large granular lymphocytes via an autocrine regulatory pathway, doi: 10.1182 / blood-2009-06-223719). Importantly, mutations in PDGFRs can cause receptors to signal in an autocrine manner, that is, independently of ligand-binding-induced dimerization. This autocrine signaling is caused by mutations in the protein sequence, and has been shown to require only the transmembrane (TM) and cytoplasmic domains of PDGFR. Thus, PDGFR receptors are an example of RTKs useful for designing CAR-T signaling domains. In some embodiments, a TM and / or cytoplasmic domain of PDGFRα and / or PDGFR0 can be used as signaling domains. In one embodiment, a T cell is transfected with nucleotide sequences encoding a CD19-targeting scFv (eg, as may be derived from the FMC63 antibody) cloned in frame with a nucleotide sequence encoding a cytoplasmic and TM domain. of a PDGFR, e.g. eg, PDGFR0, with appropriate linker sequences inserted between the components. The resulting CAR-T cell expresses anti-CD19 scFv as an antigen-binding domain, and recognition of CD19 on cells (eg, normal B cells or malignant B cells) induces CAR-T cell activation and proliferation , and supports cell survival, but does not induce cytotoxicity. These qualities of PDGFR0 signaling are known in T-cell malignancies, and other hematologic malignancies, in which PDGFR0 is dysregulated, e.g. eg, Chronic Myelogenous Leukemia (CML) and T-cell leukemia. Binding of antigen to the antigen-binding domain (scFv) induces PDGFR dimerization. In some embodiments, scFv is evaluated for the ability to specifically induce PDGFR dimerization, and can be determined by known signaling assays and functional assays. In some embodiments, a consequence of CAR-T cell activation and proliferation is the stimulation of specific promoters, e.g. eg, a promoter described herein, e.g. g., the CD69 promoter, the CD25 promoter, the TNF promoter, the VLA1 promoter, the LFAÍ promoter, and many others described herein (see, for example, Example 9), and can lead to the expression of a construct of inducible expression described herein. In some embodiments, upon binding of antigen (eg, CD19) to a first antigen-binding receptor (eg, including an anti-CD19 scFv as an antigen-binding domain and a transmembrane domain). and / or cytoplasmic expression of PDGFR) an inducible expression construct encoding a second antigen-binding receptor can be expressed. This second, induced, antigen-binding receptor can bind a tumor antigen of interest, and can include a canonical CAR-T signaling domain described herein, e.g. g., CD3 / CD28 or CD3 / 4-1BB or CD3 / CD28 / 4-1BB. Thus, such an exemplary CAR-T cell has two activities: the first is T cell activation, proliferation, and survival, as induced by signaling through the first antigen-binding receptor (which includes an anti-CD19 scFv as an antigen-binding domain and a transmembrane and / or cytoplasmic domain of PDGFR); and the second is anti-tumor cell activation, proliferation and cytotoxicity, in which the tumor cell is identified by the target of the induced antigen-binding receptor. In another embodiment, the TM and cytoplasmic domains of PDGFRα are used in place of the TM and cytoplasmic domains of PDGFR0. In yet another embodiment, nucleic acid sequences encoding an anti-CD19 scFv linked to the TM and / or cytoplasmic domains of PDGFRα, and the TM and / or cytoplasmic domains of PDGFR0 linked to anti-CD19 scFv are expressed in T cells such that a T cell expresses heterodimeric CAR constructs consisting of both the TM and cytoplasmic domains of PDGFRα and PDGFR0. Empirical analyzes of CAR-mediated signaling and function of T cells in response to antigen (eg, CD19) can be used to identify appropriate PDGFR TM and cytoplasmic domains representing PDGFRα and PDGFR0 (eg, domains that induce T cell proliferation and survival, but not cytotoxic activity, in response to antigen, eg, as shown in antigen-positive cells). In another embodiment, a cytoplasmic domain of PDGFRα and / or PDGFR0 is mutagenized to enhance or reduce one or more downstream signaling components in order to induce T cell activation, proliferation, and survival, but not cytotoxic activity, in response to antigen, e.g. eg, as shown in antigen-positive cells. Mutagenesis techniques and subsequent analysis are well known and readily apparent to one of skill in the art. In another embodiment, a cytoplasmic domain of PDGFRα and / or PDGFR0 is mutagenized to enhance or reduce one or more downstream signaling components in order to optimize induction of a specific promoter, e.g. eg, a promoter described herein, e.g. g., CD69 promoter, CD25 promoter, and / or as described in Example 9. In another embodiment, a T(i) cell expresses a first antigen-binding receptor (eg, including an scFv as an antigen-binding domain and a PDGFR transmembrane and / or cytoplasmic domain), wherein the scFv targets a first tumor antigen expressed on a tumor type, and (ii) by binding the first antigen-binding receptor to the first tumor antigen, the T cell is induced to express a second antigen-binding receptor including an scFv targeting a second tumor antigen expressed in the same tumor type. In some embodiments, the first antigen-binding receptor signals T cell activation, proliferation, and survival, but not cytotoxic activity, and the induced antigen-binding receptor (i.e., the second antigen-binding receptor) triggers the cytotoxicity. In some such embodiments, a T cell allows 'antigen synchronization', whereby cytotoxicity is induced only when both antigens successfully meet, while still promoting CAR T cell expansion and persistence. Embodiments of this type can be useful, e.g. eg, where single antigen coupling provides an insufficient therapeutic window on normal cell (ie, non-malignant cell) target destruction and toxicity. Examples of such 'antigen pairs' to which a first and a second antigen-binding receptor may target include, but are not limited to CD56 and CD138, CD56 and BMA, CD138 and BMA (Multiple Myeloma), IL- 3R (CD123) and CD33, CD123 and CLEC12A, CD33 and CLEC12A (Acute Myeloid Leukemia), CD56 and c-KIT (eg, Small Cell Lung Cancer), CEA and PSMA, PSCA AND PSMA, CEA and PSCA (Pancreatic Cancer), CA-IX and CD70 (Renal Cell Carcinoma), HER2 and EGFR, Epcam and c-MET, EGFR and IGFR (eg, Breast Cancer), MUC16 and Folate Receptor alpha, Mesothelin and Folate Receptor alpha (eg, Ovarian Cancer, Mesothelioma), and many others. In some examples one might choose to target the tumor microenvironment (TME), e.g. eg, tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC) or tumor-associated fibroblasts. Examples of relevant target antigen pairs include, but are not limited to: FAP and CD45, FAP and CSFR1, and CD45 and CSFR1. In another embodiment, a T(i) cell expresses a first antigen-binding receptor (eg, including a bispecific antibody (or part) such as an antigen-binding domain and a transmembrane and / or cytoplasmic domain of PDGFR), in which the bispecific antibody (or part) binds to a B-cell antigen (eg, CD19) and to a tumor antigen expressed on a tumor of interest, and (ii) by binding the first binding receptor to antigen to the first tumor antigen, the T cell is induced to express a second antigen-binding receptor that includes an scFv directed at a second tumor antigen expressed on the same tumor type. In some embodiments, the first antigen-binding receptor utilizes both CD19 recognition (for facilitate expansion and / or persistence) such as 'antigen pair' recognition to facilitate expansion, persistence and / or cytotoxicity. Examples of such 'antigen pairs' include, but are not limited to CD56 and CD138, CD56 and BMA, CD138 and BMA (Multiple Myeloma), IL-3R (CD123) and CD33 (Acute Myeloid Leukemia), CD56 and c -KIT (eg Small Cell Lung Cancer), CEA and PSMA, PSCA and PSMA, CEA and PSCA (Pancreatic Cancer), CA-IX and CD70 (Renal Cell Carcinoma), HER2 and EGFR, Epcam and c-MET, EGFR and IGFR (eg Breast Cancer), MUC16 and Folate Receptor alpha, Mesothelin and Folate Receptor alpha (eg Ovarian Cancer, Mesothelioma), and many others. In some examples one might choose to target the tumor microenvironment (TME), e.g. eg, tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC) or tumor-associated fibroblasts. Examples of relevant target antigen pairs include, but are not limited to: FAP and CD45, FAP and CSFR1, and CD45 and CSFR1. Domains of other receptors in the Type III RTK family, e.g. eg, CSF-IR, KIT, RK2, and FLT3, can be included in the antigen-binding receptors described herein. The disclosure is not limited to the Type III RTK family, but readily applies to the TM and cytoplasmic domains of other RTK families and receptors, e.g. g., the epidermal growth factor receptor family, the fibroblast growth factor receptor (FGFR) family, the Vascular endothelial growth factor receptor (VEGFR) family, the RET receptor family, the receptor family Eph or the Discoidin Domain Receptor (DDR) family and many others comprising receptors and families within the RTK families I - XVII. Constructs described herein can be modified to account for the different physiological means used within the different RTK families to trigger receptor signaling. In some embodiments, a transmembrane and / or cytoplasmic domain is derived from one or more components of a JAK / STAT pathway. The JAK family of signaling proteins consists of JAK1, JAK3, JAK3, and TYK2. JAK proteins homodimerize and heterodimerize to phosphorylate STAT proteins. STAT proteins thus propagate signaling. The STAT family consists of STATs 1-6. A regulatory form of STAT5, designated STAT5b, has also been identified. Almost all JAK / STAT combinations are possible, although specific cell surface receptors are known to use subsets of JAKs and STATs when signaling. Hematologic malignancies provide several examples of dysregulated JAK / STAT signaling cascades that can support cell proliferation and survival. Myeloid cell disorders, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) demonstrate mutations in JAK2 signaling, which can lead to constitutive activation of STAT3 and / or STAT5. Mutations appear most frequently in the pseudokinase domain that impacts JAK signaling and its regulation. The relationship of genotype / phenotype is complex and demonstrates a gene dosage effect such that a single allele genotype generally has a different outcome than a dual allele genotype (eg, development of ET versus PV). Both JAK2 and JAK1 have been identified as excitatory mutations in T-cell leukemias, and activation of STAT proteins has been implicated in a variety of T-cell leukemias and lymphomas. Somatic mutations in the JAK3 gene are seen in acute lymphoblastic leukemia and acute myelocytic, and in multiple myeloma and non-Hodgkin's lymphoma. Oncogenic mutations in various regulatory and negative feedback pathways that control JAK / STAT signaling have also been described. These examples provide evidence for activation of proliferative T cells driven by JAK / STAT pathways, albeit pathogenic activation when subjected to malignant mutations. Many receptors are known signals through JAK / STAT complexes. Among the RTKs, IGF-Rs, EGFR / ErbB receptors, SCFR / cKit, BDNF, Epha4, VEGFR / Flt-1 and HGFR / c-Met preferentially use JAK 1 and / or 2 and various combinations of STATs 1 , 3 and 5. RTKs also induce many other signaling cascades. Hormone receptors (GHR, TpoR, EpoR, Prolactin-R) also preferentially use JAK 1 and / or 2 (homodimers and heterodimers) and various combinations of STATs 1, 3, and 5. The TpoR can also signal through TYK2 to through a JAK2 / TYK2 complex). The main signaling pathway activated by the Prolactin Receptor pathway is the JAK / STAT pathway. The ligand (Prolactin) binds and induces receptor dimerization and activation of JAK2. JAK2 is constitutively associated with the Prolactin receptor. JAK2 phosphorylates tyrosine residues in the cytoplasmic domain of the receptor and allows the binding and phosphorylation of the STAT protein. Phosphorylated STAT5 dissociates from the receptor, dimerizes, undergoes nuclear translocation, and promoter activation of the target gene. The prolactin receptor also signals through ZAP70, Tec, PTK2, Fyn, NF-kB, and MAPK. The prolactin receptor is active on lymphocytes, and this activity is associated with lymphocyte survival during activation. Cytokine receptors from the common beta chain and common gamma chain receptor families individually use the JAK / STAT pathways to transduce signals upon ligand (ie, cytokine) binding. In all cases, ligand binding and receptor signaling requires the formation of a heteromeric complex between the specific alpha chain and the common (beta or gamma) chain. Within the family of common beta chains (IL-3, IL-5, GM-CSF) the common IL-5Ralpha / beta chain complex signals through JAKs 1 and 2 and STATs 3 and 5, while the complex of the common GM-CSF-Ralpha / beta chain uses JAKs 1 and 2 to signal through STATs 1, 3, 5 and 6. Within the family of common gamma chains (IL-2, IL-4, IL-7, IL-9, IL-13, IL-21) JAK3 typically couples, along with JAK1 and / or 2 and / or TYK2. As a consequence, STAT signaling is varied. The related TSLP cytokine shows restricted JAK utilization, as it signals through an IL-7Ralpha / TSLP-R complex to JAKs 1 and 2, and STATs 1, 3, and 5. The IL-6 receptor family, the IL-10 receptor family, and the IL-12 receptor family all share similar characteristics. The receptors form heteromeric complexes consisting of variously shared alpha chains (eg, IL-20R alpha), beta chains (eg, IL-10R-beta), lambda chains (eg, IFN -lambda-Rl), or a chain specific for the gpl30 receptor and co-receptor. This medullary allows for a considerable variety of ligand / receptor interactions and JAK / STAT signaling. All receptor complexes within these three families of cytokine receptors use JAK1 and JAK2 and TYK2, or a subset thereof, and in most cases STATs 1, 3 and 5 are the phosphorylated targets of JAK activity. with a few exceptions. TYK2 utilization frequently couples additional STAT proteins, such as STATs 4 and 6. A very similar pattern is seen within G protein-coupled receptors that signal through a JAK / STAT pathway (eg, 5- HT2A, AGTR-1, various chemokine receptors). The IL-6 receptor (IL-6R alpha / gpl30) couples with JAK complexes containing JAK1, JAK2, and TYK2. These signals in turn signal through STAT1 and STAT5. In T cells, IL-6 receptor signaling stimulates proliferation, survival, differentiation, and protection from T cell-mediated regulatory suppression. The leptin receptor signals primarily through JAK2 and STAT3 and STAT5 to induce both proliferative and anti-apoptotic signaling. The leptin receptor is expressed on T cells and is also associated with decreased T regulatory activity on T cells. The IL-12 receptor (IL-12R beta / IL-12 beta2) is expressed on T cells and is critical for the establishment of the Thl phenotype of CD4+ and CD8+ T cells. The IL-12 receptor activates JAK2 and TYK2. Specifically, IL-12RB1 associates with TYK2 and IL-12RB2 associates with JAK3. Upon activation, JAK2 phosphorylates the tyrosine residues of STAT3 and STAT4 which then translocate into the nucleus and bind to the IFN-gamma promoter, thereby driving Thl activity and differentiation. In some embodiments, a JAK / STAT-coupled receptor TM and / or cytoplasmic domain is included in an antigen-binding receptor described herein. In one embodiment, a CD19-targeting scFv (eg, as may be derived from the FMC63 antibody) is cloned in frame with the TM and cytoplasmic domains of homodimerizing or heterodimerizing receptors that have JAK / STAT coupling activities, with suitable linker sequences inserted between these components. The resulting CAR-T cell expresses anti-CD19 scFv and CD19 recognition on cells (eg, normal B cells or malignant B cells) induces CAR-T cell activation and proliferation, and supports cell survival, but does not induce cytotoxicity. These JAK / STAT signaling qualities are seen in hematologic malignancies, including T-cell malignancies in which JAK / STAT signaling is dysregulated. The binding of the antigen to the scFv will be sufficient to induce the receptor dimerization. In related embodiments, scFv will be evaluated for its ability to specifically induce PDGFR dimerization, as monitored by signaling assays and functional assays. In one embodiment, a TM and / or cytoplasmic domain is derived from IL-12 receptor chains (IL-12R-betal / IL-12beta2). In another embodiment, a TM and / or cytoplasmic domain is derived from the IL-6 receptor alpha chain. In another embodiment, a TM and / or cytoplasmic domain is derived from the leptin receptor. In another embodiment, a TM and / or cytoplasmic domain is derived from the prolactin receptor. In another embodiment, a TM and / or cytoplasmic domain is derived from a G protein-coupled receptor that couples the JAK / STAT pathway (eg, AGTR-1, 5-HT2A, PAR, PAR3, PAR4, Bradykinin- RB2, PAFR, alpha-adrenergic receptors, CXCR4, CCR2, CCR5, CCR1). In another embodiment, a TM and / or cytoplasmic domain is derived from the IL-12 receptor family (eg, IL-23R, IL-27R, but not IL-35R). In another embodiment, a TM and / or cytoplasmic domain is derived from the IL-10 receptor family. In another embodiment, a TM and / or cytoplasmic domain is derived from the IL-6 receptor family (IL-11R, CNTFR, LIFR, OSMR, GSFR, IL-31R, CTNFR). In another embodiment, a TM and / or cytoplasmic domain is derived from the gamma chain receptor family (eg, IL-2R, IL-4R, IL-7R, IL-9R, IL-13R, IL -15R, IL-21R, and the related receptor TSLPR). In another embodiment, a TM and / or cytoplasmic domain is derived from the beta chain receptor family (eg, IL-3, IL-5R, GM-CFSR). In another embodiment, a TM and / or cytoplasmic domain is derived from the homodimeric hormone receptor family (eg, GUR, TpoR, EpoR). In another embodiment, a TM and / or cytoplasmic domain is derived from the RTK family (eg, Insulin-R, EGFR / ERbB receptors, PDGF receptors, SCF-R / c-Kit, M-CSFR, FGF 1-4 receptors, EphA4, TrkB, Tie2, VEGF receptors, Mer, HGFR / c-MET). In another embodiment, a TM and / or cytoplasmic domain is derived from Type I / II interferon receptors. It is understood that for some receptors, it may be desirable to separate one or more signaling components of the receptor complex signaling while leaving an interaction with the JAK / STAT pathways intact. It is understood that methods for making such altered or mutated receptor chains are well understood and readily available to one of skill in the art. In some embodiments, a TM and / or cytoplasmic domain of a receptor that engages a JAK / STAT pathway can be used as signaling domains. In one embodiment, a T cell is transfected with nucleotide sequences encoding a CD19-targeting scFv (eg, as may be derived from the FMC63 antibody) cloned in frame with a nucleotide sequence encoding a cytoplasmic and TM domain. of a receptor that engages a JAK / STAT pathway, optionally with suitable linker sequences inserted between the components. The resulting CAR-T cell expresses anti-CD19 scFv as an antigen-binding domain, and recognition of CD19 on cells (eg, normal B cells or malignant B cells) induces CAR-T cell activation and proliferation, and supports cell survival, but does not induce cytotoxicity. In some embodiments, a consequence of CAR-T cell activation and proliferation is the stimulation of specific promoters, e.g. the CD69 promoter, CD25 promoter, TNF promoter, VLA1 promoter, LFA1 promoter, and many others described herein (see, e.g., Example 9), and can lead to expression of an inducible expression construct described herein. In some embodiments, upon binding of antigen (eg, CD19) to a first antigen-binding receptor (eg, including an anti-CD19 scFv as an antigen-binding domain and a transmembrane domain). and / or cytoplasmic of a receptor that engages a JAK / STAT pathway) an inducible expression construct encoding a second antigen-binding receptor can be expressed, is induced to be expressed. This second, induced, antigen-binding receptor can bind a tumor antigen of interest, and can include a canonical CAR-T signaling domain described herein, e.g. g., CD3 / CD28 or CD3 / 4-1BB or CD3 / CD28 / 4-1BB. Thus, such an exemplary CAR-T cell has two activities: the first is T cell activation, proliferation, and survival, as induced by signaling through the first antigen-binding receptor (which includes an anti-CD19 scFv as an antigen-binding domain and a transmembrane and / or cytoplasmic domain of a receptor that engages a JAK / STAT pathway); and the second is anti-tumor cell activation, proliferation, survival and cytotoxicity, in which the tumor cell is identified by the target of the induced antigen-binding receptor. In another embodiment, the TM and / or cytoplasmic domains of both receptor chains are used (e.g., alpha-beta, gamma / gamma, alpha / alpha, alpha / lambda, common beta, common gamma, gpl30, and gpl30 classes). specific receptors within the cited families). For example, nucleic acid sequences encoding an anti-CD19 scFv linked to such TM and / or cytoplasmic domains of different receptor chains are expressed on T cells such that a T cell expresses heterodimeric CAR constructs consisting of receptor chains. of TM and cytoplasmic domains. Empirical analyzes of CAR-mediated signaling and T cell function in response to antigen (eg, CD19) can be used to identify appropriate receptor cytoplasmic and TM domains that represent different receptor chains (eg, from different common beta participants or distinct gpl30 participants) (eg, domains that induce T-cell proliferation and / or survival, but not cytotoxic activity, in response to antigen, eg, as shown in cells antigen -positive. In another embodiment, a cytoplasmic domain of specific receptors or classes of receptor chains are mutagenized to enhance or reduce one or more downstream signaling components in order to induce cell activation, proliferation, and / or survival. T, but not cytotoxic activity, in response to antigen, e.g. eg, as shown in antigen-positive cells. Mutagenesis techniques and subsequent analysis are well known and readily apparent to one of skill in the art. In another embodiment, a cytoplasmic domain of specific receptors or classes of receptor chains is mutagenized to enhance or reduce one or more downstream signaling components in order to further optimize induction of a specific promoter, e.g. g., CD69 promoter, CD25 promoter, et alia, and / or as described in Example 9. In another embodiment, a T(i) cell expresses a first antigen-binding receptor (eg, including an scFv as an antigen-binding domain and a transmembrane and / or cytoplasmic domain of a JAK-coupled receptor). / STAT), in which the scFv targets a first tumor antigen expressed on one type of tumor, and (ii) by binding the first antigen-binding receptor to the first tumor antigen, the T cell is induced to express a second antigen-binding receptor including an scFv directed at a second tumor antigen expressed on the same type of tumor. In some embodiments, the first antigen-binding receptor signals T cell activation, proliferation, and / or survival, but not cytotoxic activity, and the induced antigen-binding receptor (i.e., the second antigen-binding receptor ) triggers cytotoxicity. In some of these embodiments, a T cell enables 'antigen timing', as described herein. This will be useful in cases where single antigen coupling provides an insufficient therapeutic window on normal cell (ie, non-malignant cell) target destruction and toxicity. Examples of such 'antigen pairs' include, but are not limited to CD56 and CD138, CD56 and BCMA, CD138 and BCMA (Multiple Myelortia), IL-3R (CD123), and CD33, CD123 and CLEC12A (Acute Myeloid Leukemia). , CD56 and c-KIT (eg, Small Cell Lung Cancer), CEA and PSMA, PSCA and PSMA, CEA and PSCA (Pancreatic Cancer), CA-IX and CD70 (Renal Cell Carcinoma), HER2 and EGFR, Epcam and c-MET, EGFR and IGFR (eg Breast Cancer), MUC16 and Folate Receptor alpha, Mesothelin and Folate Receptor alpha (eg Ovarian Cancer, Mesothelioma), and many' others. In some examples one might choose to target the tumor microenvironment (TME), e.g. eg, tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC) or tumor-associated fibroblasts. Examples of relevant target antigen pairs include, but are not limited to: FAP and CD45, FAP and CSFR1, and CD45 and CSFR1. It is understood that scFv and scFv epitope selection may be critical for successful recognition of some target antigens other than CAR-T cell recognition, in cases where the CAR-scFv receptor for the JAK / STAT construct and antigen-target overlap (eg, ERbB / EGFR receptors). Since the use of extracellular residues in the CAR-scFv receptor for the JAK / STAT construct may be limited by design, this is easily accomplished. In another embodiment, a T(i) cell expresses a first antigen-binding receptor (eg, including a bispecific antibody (or part) such as an antigen-binding domain and a transmembrane and / or cytoplasmic domain of a JAK / STAT-engaging receptor), wherein the bispecific antibody (or part) binds a B cell antigen, e.g. CD19, and a tumor antigen expressed on a tumor of interest, and (ii) by binding the first antigen-binding receptor to the first tumor antigen, the T cell is induced to express a second antigen-binding receptor that includes an scFv directed at a second tumor antigen expressed in the same type of tumor. In some embodiments, the first antigen-binding receptor utilizes both CD19 recognition (to facilitate expansion and / or persistence) and 'antigen pair' recognition to facilitate expansion and / or persistence and / or cytotoxicity. . Examples of such 'antigen pairs' include, but are not limited to CD56 and CD138, CD56 and BCMA, CD138 and BCMA (Multiple Myeloma), IL-3R (CD123), and CD33, CD123 and CLEC12A (Acute Myeloid Leukemia). , CD56 and c-KIT (eg, Small Cell Lung Cancer), CEA and PSMA, PSCA and PSMA, CEA and PSCA (Pancreatic Cancer), CA-IX and CD70 (Renal Cell Carcinoma), HER2 and EGFR, Epcam and c-MET, EGFR and IGFR (eg Breast Cancer), MUC16 and Folate Receptor alpha, Mesothelin and Folate Receptor alpha (eg Ovarian Cancer, Mesothelioma), and many others . In some examples one might choose to target the tumor microenvironment (TME), e.g. eg, tumor-associated macrophages (TAM) or myeloid-derived suppressor cells (MDSC) or tumor-associated fibroblasts. Examples of relevant target antigen pairs include, but are not limited to: FAP and CD45, FAP and CSFR1, and CD45 and CSFR1. It is understood that scFv and scFv epitope selection may be critical for successful recognition of some target antigens other than CAR-T cell recognition, in cases where the CAR-scFv receptor for the JAK / STAT construct and antigen-target overlap (eg, ERbB / EGFR receptors). Since the use of extracellular residues in the CAR-scFv receptor for the JAK / STAT construct may be limited by design, this is easily accomplished. Inducible Expression Constructs In some embodiments, an "inducible expression construct" as used herein may be or comprise a nucleic acid sequence that includes at least one promoter operably linked to a nucleotide sequence of interest, e.g. eg, a gene described herein. An inducible expression construct may comprise regulatory sequences such as transcription and translation initiation and termination codons. In some embodiments, said regulatory sequences are specific to the cell type into which an inducible expression construct is to be introduced, as appropriate. In some embodiments, such regulatory sequences are specific for a signaling pathway induced by a signaling domain described herein. An inducible expression construct may comprise a native or non-native promoter operably linked to a nucleotide sequence encoding the gene of interest. Preferably, the promoter is functional in immune cells. Operable linkage of a nucleotide sequence to a promoter is within the skill of the skilled person. The promoter can be a non-viral promoter or a viral promoter, e.g. eg, a cytomegalovirus (CMV) promoter, an SV40 promoter, an RSV promoter, or a promoter found in the murine stem cell virus long terminal repeat. In some embodiments, a promoter includes an NFAT, NF-kB, AP-1, or other recognition sequence, as examples. In some embodiments, a promoter included in an inducible expression construct described herein is an IL-2 promoter, cell surface protein promoter (eg, CD69 promoter), a cytokine promoter (eg, ., TNF promoter), a cell activation promoter (eg, CTLA4, 0X40, CD40L), or a cell surface adhesion protein promoter (eg, VLA-1 promoter). Selection of a promoter, e.g. eg, strong, weak, inducible, tissue-specific, developmental-specific, having specific kinetics of activation (eg, early and / or late activation), and / or having specific kinetics of expression of a gene induced (eg, short or long expression) is within the ordinary experience of the craftsman. In some embodiments, a promoter mediates rapid and sustained expression, measured in days (eg, CD69). In some embodiments, a promoter mediates delayed, inducible late expression (eg, VLA1). In some embodiments, a promoter mediates fast, transient expression (eg, TNF, immediate early response genes, and many others). Upon binding to antigen by an antigen-binding receptor, a signal can be transduced from a signaling domain of an antigen-binding receptor described herein to an inducible expression construct, e.g. using a known route (see, e.g., Chow et al., Mol. Cell. Biol. 19:2300-2307 (1999); Castellanos et al., J. Immunol. 159:5463-73 ( 1997), Kramer et al., JBC 270:6577-6583 (1995), Gibson et al., J. Immunol. 179:3831-40 (2007)); Tsytsykova et al., J. Biol. Chem. 271:3763-70 (1996); Goldstein et al., 1 Immunol. 178:201-10 (2007)). Thus, upon binding of an antigen, an antigen-binding receptor activates a signal transduction pathway that leads to induction of expression (eg, by binding of a transcription factor to a promoter described herein). memory). Genes for Expression Constructs Any gene may be included in an expression construct described herein (eg, a constitutive expression construct or an inducible expression construct), and the present disclosure is not limited to any particular gene. Illustrative, non-limiting, types of genes that can be included in an expression construct include, e.g. eg genes that encode polypeptides (eg. z polypeptide antigens and / or therapeutic peptides), antibodies (eg, antigen-binding fragments of antibodies and / or fusion proteins comprising an antibody or antigen-binding fragment(s), cytokines, chemokines, receptors for cytokines, chemokine receptors, toxins, agents that target the tumor microenvironment, and agents that support the growth / proliferation of immune cells. In some examples, a gene sequence included in an expression construct is transcribed and then translated. In other cases, transcribed therapeutics have utility as genes, as is known for RNAi, miRNA, shRNA, and other classes of regulatory RNAs, without limitation. 1. Expressed Polypeptides In some embodiments, a cellular therapeutic agent described herein may include an expression construct (eg, a constitutive expression construct or an inducible expression construct) that encodes a polypeptide antigen (or a fragment thereof, e.g. g., a fragment that includes an epitope). In some embodiments, an expression construct includes a nucleotide sequence that encodes a tumor antigen. Tumor antigens are known in the art and include, for example, glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin 0, alpha-fetoprotein (AFP), lecithin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX , human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-la, p53, prosternum , PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCIA-1), MAGE, ELF2M, neutrophil elastase, ephrinB2, CD22, insulin growth factor (IGF)-I, IGF- II, receptor for IGF-I and mesothelin. In some embodiments, a tumor antigen is or comprises one or more cancer antigen epitopes associated with a malignant tumor. Malignant tumor antigens that include such epitopes include, e.g. eg, tissue-specific antigens such as MART-1, tyrosinase, and GP 100 in melanoma and prosthetic acid phosphatase (PAP) prostate-specific antigen (PSA) in prostate cancer. Other tumor antigens belong to the group of transformation-related molecules such as the HER-2 / Neu / ErbB-2 oncogene. Still another group of tumor antigens are onco-fetal antigens such as carcinoembryonic antigen (CEA). In B-cell lymphoma the tumor-specific immunoglobulin constitutes a tumor-specific immunoglobulin antigen that is unique to the individual tumor. B-cell differentiation antigens such as CD19, CD20, and CD37 are other tumor antigens in B-cell lymphoma. Some of these antigens (eg, CEA, HER-2, CD19, CD20, idiotype) have been used with limited success as targets for passive immunotherapy with monoclonal antibodies. A tumor antigen described herein may be a tumor specific antigen (TSA) or a tumor associated antigen (TAA). A TSA is (or is believed to be) unique to tumor cells and is not produced by other cells in the body (eg, not produced to a significant degree by other cells). A TAA is not unique to a tumor cell and instead is also expressed on a normal cell (eg, expressed under conditions that fail to induce a state of immunological tolerance to the antigen). For example, TAAs may be antigens that are expressed on normal cells during fetal development when the immune system is immature and unable to respond, or they may be antigens that are normally present at extremely low levels on normal cells but are expressed at higher levels in tumor cells. Non-limiting examples of TSA or TAA antigens include differentiation antigens such as MART-l / MelanA (MART-I), gplOO (Pmel 17), tyrosinase, TRP-1, TRP-2, and tumor-specific multi-lineage antigens such as MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, p15; overexpressed embryonic antigens such as CEA; overexpressed oncogenes and mutated tumor suppressor genes such as p53, Ras, HER-2 / neu; unique tumor antigens resulting from chromosomal translocations such as BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR; and viral antigens such as Epstein Barr virus EBVA antigens and human papillomavirus (HPV) E6 and E7 antigens. Other tumor antigens include TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE, NY-ESO, erbB, p185erbB2, p180erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19 -9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-catenin, CDK4, Mum-1, p15, p16, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, beta-HCG, BCA225 , BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2 binding protein\cyclophilin C associated protein, TAAL6, TAG72, TLP, MUC16, IL13Ra2, FRo, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FOLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalyl cidase C, MUC- 1, CFC1B, integrin alpha 3 chain (from a3bl, a laminin receptor chain), and TPS. In some embodiments, a tumor antigen is CD19, CD20, CD22, CD30, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL- 1 / CLECK12A, ROR1, Glypican 3 (GPC3), Mesothelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glycolipid F77, EGFRvIII, GD-2, MY-ESO-1 or MAGE A3. Additional tumor antigens can be identified, e.g. eg, by sequencing of tumor and exorn genomes, and / or by high-sensitivity mass spectrometry analysis of the tumor proteome, any of which can be used in the methods described herein. In some embodiments, a tumor antigen is a membrane protein generic or "maintenance", e.g. i.e., found in every single cell. In some embodiments, a tumor antigen is a tumor stem cell marker. In some embodiments, a tumor antigen is a neoantigen (ie, an antigen that arises in a tumor itself, eg, due to aberrant proliferation). In some embodiments, an expressed polypeptide is included as part of a fusion protein, e.g. eg, a fusion protein that includes the polypeptide antigen and an antibody or antibody fragment described herein. In some embodiments, a fusion protein is or includes a polypeptide antigen fused to the amino (N) terminus of another protein, eg, a polypeptide antigen fused to the amino (N) terminus of an antigen-binding protein (eg. antibody or antibody fragment described herein, or a scaffold protein described herein (eg, Kunitz-like domain, ankyrin repeat domain, lipoclains, Type III fibronectin domain, CD19 variant protein, or variant specific marker for B cells described herein)). In some embodiments, a fusion protein is or includes a polypeptide antigen fused to the amino terminus of an antibody light chain, or a fragment thereof. In some embodiments, a fusion protein is or includes a polypeptide antigen fused to the amino terminus of an antibody heavy chain, or part thereof. In some embodiments, a fusion protein is or includes a polypeptide antigen fused to the carboxyl (C) terminus of another protein, eg, a polypeptide antigen fused to the carboxyl (C) terminus of an antigen-binding protein (eg. antibody or antibody fragment described herein, or a scaffold protein described herein (eg, fibronectin Type III domain, variant CD19 protein, or variant specific marker for B cells described herein) ). In some embodiments, a fusion protein is or includes a polypeptide antigen fused to the carboxy terminus of an antibody light chain, or a fragment thereof. In some embodiments, a fusion protein is or includes a polypeptide antigen fused to the carboxyl terminus of an antibody heavy chain, or part thereof. In some embodiments, an expressed polypeptide antigen (or a fragment thereof) is expressed on the surface of the cellular therapeutic agent and / or is secreted by the cellular therapeutic agent and / or binds to the surface of a tumor cell. Although any polypeptide can be expressed from an expression construct described herein, in particular embodiments a polypeptide is selected that is a target of (eg, binds to) an antigen-binding protein described herein ( eg, an antibody (eg, a bispecific antibody or multispecific antibody or fragment thereof), an antibody fusion protein, or an antibody-drug conjugate). In some embodiments, the antibody or antibody fusion protein can be e.g. eg, a known therapeutic antibody (eg, one displaying ADCC or CDC), a therapeutic fusion protein, or a therapeutic antibody-drug conjugate. In some embodiments, a nucleic acid encoding a polypeptide antigen that binds to one or more known antibodies or antibody-drug conjugates can be included in an expression construct described herein. Several review articles have been published describing useful anti-tumor antibodies (see, eg, Adler et al., Hematol. Oncol. Clin. North Am. 26:447-81 (2012); Li et al., Drug Discov Ther 7:178-84 (2013);Scott et al., Cancer Immun.12:14 (2012);and Sliwkowski et al., Science 341:1192-1198 (2013)). Table 1 presents a non-exhaustive list of certain human polypeptide antigens targeted by known, available antibody agents, and notes certain anticancer indications for which antibody agents have been proposed to be useful: TABLE 1 Human Antigen Antibody (commercial or scientific name) Indication against cancer CD2 Siplizumab Non-Hodgkin Lymphoma CD3 UCHT1 Peripheral or Cutaneous T-Cell Lymphoma CD4 HuMax-CD4 CD19 SAR3419, MEDI-551 Diffuse Large B-Cell Lymphoma CD19 and CD3 or CD22 Bispecific antibodies such as Blinatumomab, DT2219ARL Non-Hodgkin lymphoma CD20 Rituximab, Veltuzumab, Tositumomab, Ofatumumab, Ibritumomab, Obinutuzumab, Malignant B-cell tumors (non-Hodgkin lymphoma, Chronic lymphocytic leukemia) CD22 (SIGLEC2) Inotuzumab, tetraxetan,CAT-8015, DCDT2980S, DCDT2980S Chemotherapy-resistant hairy cell leukemia, Hodgkin lymphoma CD30 Brentuximab vedotin CD33 Gemtuzumab ozogamicin (Mylotarg) Acute myeloid leukemia CD37 TRU-016 Chronic lymphocytic leukemia CD38 Daratumumab Multiple myeloma, hematologic tumors CD40 Lucatumumab Non-Hodgkin lymphoma CD52 Alemtuzumab (Campath) Chronic lymphocytic leukemia CD56 (NCAM1) Lorvotuz umab CD66e Small Cell Lung Cancer (CEA) Labetuzumab Breast, colon and lung tumors CD70 SGN-75 Non-Hodgkin lymphoma CD74 Milatuzumab Non-Hodgkin lymphoma CD138 (SYND1) BT062 Multiple Myeloma CD152 (CTLA-4) Ipilimumab Metastatic melanoma CD221 (IGF1R) AVE1642, IMC-A12, MK-0646, R150, CP 751871 Glioma, lung, breast, head and neck, prostate and thyroid cancer CD254 (RANKL) Denosumab Breast carcinoma and prostate CD26Í (TRAILR1) Mapatumumab Colon, lung and pancreas tumors CD262 (TRAILR2) HGS-ETR2, CS-1008 and malignant hematological tumors CD326 (Epcam) Edrecolomab, 17-1A, IGN101, Catumaxomab, Adecatumumab Colon and rectal cancer, ascites malignant, epithelial tumors (breast, colon, lung) CD309 (VEGFR2) IM-2C6, CDP791 Solid tumors derived from epithelium CD319 (SLAMF7) HuLuc63 Multiple Myeloma CD340(HER2) Trastuzumab, Pertuzumab, Ado-trastuzumab emtansine Breast cancer CAIX (CA9 ) cG250 Renal cell carcinoma EGFR (c-erbB) Cetuximab, Panitumumab, nimotuzumab, and 806 Solid tumors, including glioma, lung, breast, colon, and head and neck tumors EPHA3(HEK) KB004, IIIA4 Tumors of the lung, kidney, and colon, melanoma, glioma and hematological malignancies Epsialin a Epitumomab Epithelial ovarian tumors FAP Sibrotuzumab and F19 Colon, breast, lung, pancreas and head and neck tumors HLA-DR beta Apolizumab Chronic lymphocytic leukemia, non-Hodgkin lymphoma FOLR-1 Farletuzumab Ovarian tumors 5T4 Anatumomab Non-small cell lung cancer GD3 / GD2 3F8, ch 14.18, KW-2871 Neuroectodermal and epithelial tumors gpA33 huA33 Colorectal carcinoma GPNMB Glembatumumab Breast cancer HER3(ERBB3) MM-121 Breast, colon, lung, ovarian and prostate tumors Integrin aV03 Etaracizumab Tumor vasculature Integrin 05 (31 Volociximab Tumor vasculature Lewis-Y antigen hu3S193, IgN311 Breast, colon, lung and prostate tumors MET (HGFR) AMG 102, METMAB, SCH900105 Breast, ovarian and lung tumors Mudna-l / CanAg Pemtumomab, oregovomab, Cantuzumab Tumors of breast, colon, lung and ovary PSMA ADC, J591 Prostate cancer Phosphatidylserine Bavituximab Solid tumors TAG-72 Minretumomab Breast, colon and lung tumors Tenascin 81C6 Glioma, tumors of breast and prostate VEGF Bevacizumab Tumor vasculature In some embodiments, a cellular therapeutic agent that includes an expression construct (eg, a constitutive expression construct or inducible expression construct) encoding one or more of said polypeptide antigens is administered to a subject in combination with one or more more of these (or other) known antibodies. Antibody-drug conjugates are known and include, e.g. eg, brentuximab vedotin (ADCETRIS®, Seattle Genetics); ado-trastuzumab-emtansine (KADCYLA ®, Roche); Gemtuzumab ozgamicin (Wyeth); CMC-544; SAR3419; CDX-011; PSMA-ADC; BT-062; and IMGN901 (see, e.g., Sassoon et al. Methods Mol. Biol. 1045: 1-27 (2013); Bouchard et al., Bioorganic Med. Chem Lett. 24: 5357-5363 (2014)). In some embodiments, a nucleic acid encoding a polypeptide antigen that binds to one or more of these known antibody-drug conjugates can be included in an expression construct described herein. In some embodiments, a cellular therapeutic agent including an expression construct encoding one or more of said polypeptide antigens is administered to a subject in combination with one or more of these (or other) known antibody-drug conjugates. In some embodiments, an expressed polypeptide is included as part of a fusion protein. For example, an expression construct may encode a fusion protein comprising an expressed polypeptide described herein (eg, a target polypeptide for an antibody, an antibody fusion protein, and / or an antibody-drug conjugate). ) and a second polypeptide (eg, a scaffold protein described herein (eg, fibronectin Type III domain, variant CD19 protein, or variant specific marker for B cells described herein), a antibody or fragment thereof, eg, Fab fragment, Fab' fragment, F(ab') fragment 2 , scFv fragment, Fv fragment, dsFv diabody, dAb fragment, Fd' fragment, Fd fragment, CDR region, a cameloid antibody, a masked antibody (eg, Probody®), a single-chain or Tandem diabody (TandAb®), a VHH, an Anticalin®, a single domain antibody (eg, Nanobody®), an ankyrin repeat protein or DARPIN®, an Avimer®, an Adnectin®, an Affilin®, an Affibody ®, a Fynomer®, or a Centyron®) that targets (eg, binds to) a tumor antigen such as a tumor antigen described herein. An illustrative cellular therapeutic agent is depicted in Figure 9. As shown in Figure 9, an illustrative cellular therapeutic agent includes an antigen-binding receptor, which includes an antigen-binding domain (eg, an antigen-binding domain). antigen-binding domain described herein) and a signaling domain (eg, a signaling domain described herein). The cellular therapeutic agent also includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes an scFv-CD30 fusion protein. Upon binding of the antigen-binding domain to an antigen in a tumor cell (eg, after administration to a subject), the signaling domain induces expression of the scFv-CD30 fusion protein. The scFv portion of the fusion protein binds to a second antigen on the tumor cell, localizing CD30 (ie, the scFv fusion partner) to the tumor cell. In this illustrative embodiment, ADCETRIS® (brentuximab vedotin; Seattle Genetics) is subsequently administered to target CD30. Upon binding to CD30 of the scFv-CD30 fusion protein (which binds to the tumor cell), ADCETRIS® leads to the killing of proliferating tumor cells. In another embodiment, a cellular therapeutic agent includes a chimeric antigen receptor (CAR) on its surface, which includes an antigen-binding domain (eg, an antigen-binding domain described herein) and an antigen-binding domain. signaling (eg, a signaling domain described herein). The cell therapeutic agent also includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes CD30. Upon binding of the antigen-binding domain to an antigen on a tumor cell (eg, after administration to a subject), the signaling domain induces expression of CD30 on its surface. In this illustrative embodiment, ADCETRIS is used (eg, administered to the subject) to target CD30 on the cell therapeutic agent and, upon binding to CD30 on a surface of the cell therapeutic agent, results in the local killing of CD30. proliferating tumor cells. These are a few illustrative cellular therapeutic agents, and do not limit the present disclosure. For example, any of the antigens listed in Table 1 can be encoded by an expression construct, either alone or as part of a fusion protein (eg, a fusion protein that includes a polypeptide that targets a tumor antigen). Any of these cellular therapeutic agents can be used alone or in combination with a corresponding antibody or antibody-drug conjugate listed in Table 1. In some embodiments, an expression construct (eg, a constitutive expression construct or inducible expression construct) can encode a fusion protein that comprises a polypeptide that is a target for (eg, binds to) one or more known radioactive antibodies (eg, a radioactive antibody used in radioimmunotherapy (RIT)) and a second polypeptide (eg, a scaffold protein described herein (eg, a domain Type III fibronectin protein, variant CD19 protein, or variant specific marker for B cells described herein), an antibody or fragment thereof, eg, Fab fragment, Fab' fragment, F(ab') fragment 2 , scFv fragment, Fv fragment, dsFv diabody, dAb fragment, Fd' fragment, Fd fragment, or CDR region) that targets (eg, binds to) a tumor antigen such as a described tumor antigen in this memory. Radioactive antibodies are known (eg, BEXXAR® (Corixa), ZEVALIN® (Spectrum Pharmaceuticals), Actimab-A (actinium-225-linked anti-CD33 lintuzumab antibody; Actinium Pharmaceuticals), and beta-emitting monoclonal antibodies, e.g. eg, Lul77 (see, eg, Nordic Nano). Furthermore, any antibody described herein may be linked, directly or indirectly, to a radioisotope including, e.g. g., beta emitters, Auger emitters, conversion electron emitters, alpha emitters, and low-energy photon emitters. Illustrative radioisotopes can include low range beta emitters such as 90 Y, 32 Q, 186 Re / 188 Re; 166 hey, 76 Ace / 77 Ace, 89 Mr, 153 YE; mid-range beta emitters such as 131 YO, 177 Lu, 67 wow, l61 Tb, 105 Rh; low energy beta emitters such as 45 Ca or 35 Yes; conversion or Auger issuers such as 51 Cr, 67 Ga, 99m ct, U1 ln, 114n Yum, 123 YO, 125 YO, 201 YOU; and alpha emitters such as 212 B, 213 B, 223 Ac, 225 Ac, 212 pb, 255 hm, 223 Ra, 149 Tb and 221 At. Suitable linkers are known in the art and include, for example, prosthetic groups, non-phenolic linkers (derivatives of N-succimidyl-benzoates; dodeca borate), chelating moieties of both macrocyclic and acyl chelators such as 1,4,7-acid derivatives. ,10-tetraazadchlorododecane-l,4,7,10,tetraacetic acid (DOTA), derivatives of diethylenetriaminepentaacetic acid (DTPA), derivatives of S-2-(4-isothodanatobenzyl)-l,4,7-tr acid l,4,7-tráacetic azacyclononane (NOTE) and derivatives of l,4,8,ll-tetraazacyclodocedan-1,4,8,ll-tetraacetic acid (TETA) and other chelating moieties. Radiolabeling of antibodies of this type is known in the art (see, e.g., Barbet et al., Methods Mol. Biol. 907:681-97 (2014); Steiner et al., Clin. Cancer Res. 17 :6406 (2011); Goldenberg, J. Nucí. Med. 43:693-713 (2002)). In some embodiments, an expression construct (eg, a constitutive expression construct or inducible expression construct) includes a gene that encodes a polypeptide antigen that is a target for one or more additional cellular therapeutic agents, e.g. eg, CAR-T cells. CAR-T cells are known in the art and include CAR-T cells that target e.g. eg, CD19, CD20, CD22, CD30, CD33, CD171, CD133, EphA2, estrogen receptor, progesterone receptor, EGF receptor (EGFR), EGFR mutants (eg, EGFRvIII), CEA, GPC3, HER-2, GD2, alpha-fetoprotein (AFP), CA19-9, prostate-specific antigen (PSA), and BCMA (see, e.g., Juno Therapeutics; Bellicum; Kite Pharma; Cellectis; Hillerdal et al., BioDrugs 29:75-89 (2015), Magee et al., Discov. Med. 18:265-71 (2014), Kakarla et al., Cancer J. 20:151-155 (2014)). CAR-T cells generally kill only cells that express a particular antigen recognized by a particular type of CAR-T cell. A known problem with the use of CAR-T cells involves tumor heterogeneity. Solid tumors, e.g. For example, they are characterized by a heterogeneous distribution of antigens. In some embodiments, methods and compositions of the disclosure increase the number and / or types of tumors that can be recognized by a particular CAR-T cell. For example, in some embodiments, an expression construct described herein expresses a target antigen for one or more known CAR-T cells. In some of these embodiments, following expression of a target antigen, said target antigen is secreted from of a cellular therapeutic agent and can bind on or near a tumor cell. Upon subsequent treatment with a CAR-T cell that targets the target antigen, said CAR-T cell binds to the target antigen expressed on or near the tumor cell. Some of these methods thus allow the use of a specific CAR-T cell to target a tumor cell that it would not otherwise target (ie, a tumor cell that does not express a relevant target antigen). In some embodiments, a cellular therapeutic agent described herein may include an expression construct (eg, a constitutive expression construct or an inducible expression construct) that encodes a polypeptide target (eg, a CAR dyne). ) for one or more additional therapeutic agents (eg, CAR-T). Without wishing to be bound by theory, it is believed that an expressed polypeptide target (eg, CAR target) may provide a targeting and / or killing advantage and / or may provide a proliferative and / or survival advantage for TIL and / or TCR T cells (eg, resulting in differentiation of a memory T cell subset and / or a long-lived NK cell subset). A polypeptide antigen to be expressed by an expression construct described herein is not limited to any particular polypeptide or part thereof, provided that an additional cellular therapeutic agent (eg, CAR-T cell) is available and / or can be genetically engineered to recognize and bind to said polypeptide target. In some embodiments, a polypeptide target is a polypeptide that is not a tumor-associated antigen. In some embodiments, the target is a tumor antigen described herein, e.g. g., CD19, CD20, CD22, ROR1, Glypican 3 (GPC3), mesothelin, CD33 / IL3Ra, c-Met, PSMA, glycolipid F77, EGFRvIII, GD-2, NY-ESO-1, or MAGE A3. In some embodiments, such a polypeptide target can be encoded by an expression construct, either alone or as part of a fusion protein (eg, a fusion protein that includes a polypeptide that targets an antigen). tumor as described herein). Any of these cellular therapeutic agents can be used alone or in combination with a corresponding additional cellular therapeutic agent (eg, CAR-T cell). In some embodiments, an expression construct encodes a therapeutic peptide. For example, a therapeutic peptide can block the interaction of TGF0 with a TGF0 receptor, and / or block the interaction of PD-1 with PD-L1. Additional therapeutic peptides are known in the art. In some embodiments, an expression construct encodes a TLR agonist, an NK ligand, and / or an NKT ligand. In some embodiments, an expressed polypeptide includes a signal sequence, e.g. eg, to drive secretion of the polypeptide from a cellular therapeutic. Signal sequences and their uses are known in the art. In some embodiments, a constitutive expression construct encodes one or more polypeptides described herein. In some embodiments, an induced expression construct encodes one or more polypeptides described herein. In some embodiments, a polypeptide described herein may be additionally or alternatively produced and / or purified using known methods. In some embodiments, such a produced and / or purified polypeptide as described herein can be used as a proteinaceous therapeutic. 2, Expressed Antibodies In some embodiments, a cellular therapeutic agent includes an expression construct (eg, a constitutive expression construct or an inducible expression construct) that encodes an antibody (or a fragment thereof) and / or a fusion protein that comprises an antibody or a fragment thereof. Antibodies include, e.g. intact IgG, IgE, and IgM, bi- or multi-specific antibodies (eg, Zybodies®, etc.), single-chain Fvs, polypeptide-Fc fusions, Fabs, cameloid antibodies, masked antibodies (eg, Probodies®), Small Modular ImmunoPharmaceuticals ("SMIPsTM"), Single or Tandem Chain Diabodies (TandAb®), VHHs, Anticalins®, Nanobodies©, Minibodies, BiTE©s, Ankyrin Repeat Proteins or DARPINs®, Avimers®, a DART, a TCR-like antibody, Adnectins®, Affilins®, Trans-bodies®, Affibodies®, a TrimerX®, MicroProteins, Fynomers®, Centyrins® and a KALBITOR®. Illustrative antibodies are listed in Table 1. In some embodiments, an antibody targets PD-1, TIM-3, LAG-3, IDO, A2AR, TGFbeta, CD47, or another protein involved in an immunosuppressive pathway. For example, an inducible expression construct can encode an antibody fragment (eg, anti-PDl scFv; anti-PD-LL scFv; anti-CD39 scFv; or anti-CD73 scFv). In some embodiments, a cellular therapeutic agent includes an expression construct that encodes a fusion protein comprising an antibody (or fragment thereof) and an additional polypeptide described herein. In some embodiments, an expression construct described herein encodes a fusion protein comprising an antibody (or antigen-binding fragment thereof) and a target for one or more additional cellular therapeutic agents (eg, a target CAR-T). An antibody (or fragment) can be selected to bind, e.g. eg, to a tumor antigen (eg, a TAA or TSA described herein), and its fusion partner may include a target for one or more additional cellular therapeutic agents. Antibodies (or antigen-binding fragments) of this type include, e.g. g., a monoclonal antibody (mAb), Fv, scFv, a VHH domain, a diabody, a nanobody, etc. In one example, an expression construct encodes a fusion protein of a mAb (eg, a mAb associated anti-tumor antigen or an antigen-binding fragment) and CD19 or a fragment thereof (eg, a CD19 Ig domain). In some embodiments, an antibody (or fragment) binds to an antigen expressed on various cell types. In some embodiments, an antibody (or fragment) binds to a tumor-selective antigen. In some embodiments, an antibody (or fragment) binds to a tumor-selective, but non-specific antigen. In some embodiments, an antibody (or fragment) binds to a tumor antigen associated with a hematologic malignancy. In some embodiments, an antibody (or fragment) binds to a tumor antigen associated with a solid tumor. In some embodiments, an antibody (or fragment) binds to one or more of CD3, CD16, CD19, CD20, CD22, CD72, CD180, ROR1, CCL-1, Glypican 3 (GPC3), mesothelin, CD33 / IL3Ra, c -Met, PSMA, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 and MAGE A3. In some embodiments, an antibody (or fragment) binds to a B cell-specific marker described herein, e.g. g., CD19, CD20, CD21, CD22, CD24, CD79a, CD79b, ROR1, or BCMA. In some embodiments, an antibody (or fragment) binds to a fragment or part of a B-cell-specific marker. For example, in some embodiments, an antibody (or fragment) binds to a large extracellular loop (eg, a large extracellular loop). , at least a part of amino acids 163-187) of CD20 (see Du et al JBC Vol. 282, No. 20, 2007, pp. 15073-15080). Some of these embodiments can be used, e.g. g., in combination with a cellular therapeutic agent, e.g. eg, a CAR-T cell that targets a specific marker for B cells (eg, to treat a B-cell tumor). Following administration of a cellular therapeutic agent (eg, a CAR-T cell) to a subject, expansion of the CAR-T cell may mediate efficacy, which in certain cases may require continuous antigen stimulation. For a CAR-T cell that targets a specific marker for B cells, normal B cells in a subject can provide the antigen target to the CAR-T cell, providing stimulation and expansion of CAR-T cells. However, B cells (expressing the B cell-specific marker) are killed by the CAR-T cell along with B cell tumors expressing the same B cell-specific marker. Thus, in some embodiments, a expression encodes a fusion protein comprising an antibody (or antigen-binding fragment thereof) and a marker specific for B cells. An antibody (or fragment) may be selected for binding, e.g. g., to a tumor antigen (eg, a TAA or TSA described herein), the B cell-specific marker may be a target for a further cellular therapeutic agent, e.g. eg, a CAR-T cell. In some of these embodiments, a fusion protein binds to a tumor antigen, and a B cell-specific marker (bound to the tumor antigen) provides cell stimulation and expansion for an additional cellular therapeutic agent, e.g. eg, a CAR-T cell, administered to a subject. An illustrative embodiment of a cellular therapeutic agent is depicted in Figure 2. As shown in Figure 2, a cellular therapeutic agent includes an antigen-binding receptor on its surface, which includes an antigen-binding domain (eg. eg, an antigen-binding domain described herein) and a signaling domain (eg, a signaling domain described herein). The cellular therapeutic agent also includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes a fusion protein of the IgC domain of scFv-CD19. Upon binding of the antigen-binding domain to a first antigen on a tumor cell, the signaling domain induces expression of the scFv-CD19 IgC domain fusion protein. The scFv portion of the fusion protein binds to a second antigen on the tumor cell (eg, a tumor-associated antigen, TAA), localizing CD19 (ie, the scFv fusion partner) to the tumor cell . The tumor cell is thus "decorated" with CD19. An additional cellular therapeutic agent (eg, a CAR-T that includes an antigen-binding domain that binds CD19) binds to CD19 of the scFv-CD19 fusion protein (which binds to the tumor cell) , and subsequently kills the tumor cell "decorated" with CD19. As depicted in Figure 2, the induced scFv-CD19 fusion protein can also bind to a second tumor cell, which does not express the first antigen, allowing the CAR-T cell to bind to and kill the second tumor cell. Figure 2 illustrates an illustrative method for overcoming tumor heterogeneity with respect to expressed antigens. Another illustrative embodiment of a cellular therapeutic agent is depicted in Figure 3. As shown in Figure 3, a cellular therapeutic agent includes an antigen-binding receptor on its surface, which includes an antigen-binding domain (eg. eg, an antigen-binding domain described herein) and a signaling domain (eg, a signaling domain described herein). The cellular therapeutic agent further includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes an scFv-EGFR fusion protein. Upon binding of the antigen-binding domain to a first antigen on a tumor cell, the signaling domain induces expression of the scFv-EGFR fusion protein. The scFv portion of the fusion protein binds to a second antigen on the tumor cell, localizing EGFR (ie, the scFv fusion partner) to the tumor cell. The tumor cell is thus "decorated" with EGFR. An additional cellular therapeutic agent (eg, a CAR-T that includes an EGFR-binding antigen-binding domain) can be used to bind the EGFR of the scFv-EGFR fusion protein (which binds to the tumor cell), and subsequently kills the EGFR-"decorated" tumor cell. Another illustrative cellular therapeutic agent is depicted in Figure 4. As shown in Figure 4, a cellular therapeutic agent includes a first antigen-binding receptor on its surface, which includes a first antigen-binding domain (eg, ., a binding domain to antigen described herein) and a signaling domain (eg, a signaling domain described herein). The cellular therapeutic further includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes two proteins: (i) an scFv-CD19 fusion protein; and (ii) a CAR that includes a second antigen-binding domain (which binds to CD19). Upon binding of the first antigen-binding domain to a first antigen on a tumor cell, the signaling domain induces expression of the scFv-CD19 fusion protein and CAR. The scFv portion of the scFv-CD19 fusion protein binds to a second antigen on the tumor cell, localizing CD19 (ie, the scFv fusion partner) to the tumor cell. The tumor cell is thus "decorated" with CD19. The cellular therapeutic agent subsequently binds to the scFv-CD19 fusion protein CD19 (which binds to the tumor cell), mediated by CAR expression. Alternatively or additionally, an additional cellular therapeutic agent (i.e., a CAR-T that includes an antigen-binding domain that binds CD19) can be used to bind to CD19 from the scFv-CD19 fusion protein (which binds to the tumor cell), and kills the tumor cell "decorated" with CD19. In some embodiments, the scFv-CD19 fusion protein and the CAR may be expressed at the same time (eg, using the same or separate promoters), or may be expressed at different times. In some embodiments, an inducible expression construct includes a first promoter for expressing the scFv-CD19 fusion protein, and includes a second promoter for expressing a second CAR. For example, a first promoter may mediate rapid expression of the scFv-CD19 fusion protein, and a second promoter may mediate delayed expression of the second CAR. In some embodiments, a CAR includes a second signaling domain that can drive constitutive or inducible expression of the scFv-CD19 fusion protein and / or the CAR (eg, to "self-amplify" the cellular therapeutic agent). ). Figure 5 depicts an illustrative cellular therapeutic agent encoding a constitutively expressed CAR. As shown in Figure 5, a cellular therapeutic agent includes a first antigen-binding receptor on its surface, which includes a first antigen-binding domain (eg, an antigen-binding domain described herein ) and a signaling domain (eg, a signaling domain described herein). The cellular therapeutic further constitutively expresses a CAR that includes a second antigen-binding domain (which binds CD19). The cellular therapeutic agent also includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes an scFv-CD19 fusion protein. Upon binding of the first antigen-binding domain to a first antigen on a tumor cell, the signaling domain induces expression of the scFv-CD19 fusion protein. The scFv part of the scFv-CD19 fusion protein binds to a second antigen on the tumor cell, localizing CD19 (ie, the scFv fusion partner) to the tumor cell. The tumor cell is thus "decorated" with CD19. The cellular therapeutic agent subsequently binds to the scFv-CD19 fusion protein CD19 (which binds to the tumor cell), mediated by the constitutively expressed CAR. In this embodiment, the cellular therapeutic agent is self-amplifying, because CD19 targeting CAR triggers the release of more scFv-CD19 fusion protein. Alternatively or additionally, an additional cellular therapeutic agent (i.e., a CAR-T that includes an antigen-binding domain that binds CD19) can be used to bind CD19 to the scFv-CD19 fusion protein (which binds to the tumor cell), and kills the tumor cell "decorated" with CD19. Another illustrative cellular therapeutic agent is depicted in Figure 6. As shown in Figure 6, a cellular therapeutic agent includes a first antigen-binding receptor on its surface, which includes a first antigen-binding domain (eg, ., an antigen-binding domain described herein) and a signaling domain (eg, the antigen-binding domain is not a CAR). The cellular therapeutic agent shown in Figure 6 (left) further includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes two proteins: (i) a fusion protein scFv-CD19; and (ii) a CAR that includes a second antigen-binding domain (which binds CD19). Upon binding of the first antigen-binding domain to a first antigen on a tumor cell, the signaling domain induces expression of the scFv-CD19 fusion protein and CAR. The scFv portion of the scFv-CD19 fusion protein binds to a second antigen on the tumor cell, localizing CD19 (ie, the scFv fusion partner) to the tumor cell. The tumor cell is thus "decorated" with CD19. The cellular therapeutic agent subsequently binds to the scFv-CD19 fusion protein CD19 (which binds to the tumor cell), mediated by CAR expression. The cellular therapeutic shown in Figure 6 (right) additionally constitutively expresses a CAR that includes a second antigen-binding domain (which binds CD19) and also includes an inducible expression construct (eg. , an inducible expression construct described herein), which encodes a scFv-CD19 fusion protein. Upon binding of the first antigen-binding domain to a first antigen on a tumor cell, the signaling domain induces expression of the scFv-CD19 fusion protein. The scFv portion of the scFv-CD19 fusion protein binds to a second antigen on the tumor cell, localizing CD19 (ie, the scFv fusion partner) to the tumor cell. The tumor cell is thus "decorated" with CD19. The cellular therapeutic agent subsequently binds to the scFv-CD19 fusion protein CD19 (which binds to the tumor cell), mediated by the constitutively expressed CAR. Figure 7 depicts additional illustrative cellular therapeutic agents that include inducible expression constructs that include various genes. Another illustrative cellular therapeutic agent includes an antigen-binding receptor described herein, and also includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes an scFv-CD19 fusion protein. . The scFv part of the fusion protein binds to a tumor antigen. Upon binding of the antigen-binding domain to an antigen on a tumor cell (eg, after administration to a subject), the signaling domain induces expression of the scFv-CD19 fusion protein. The scFv portion of the fusion protein binds to a second antigen on the tumor cell, localizing CD19 (ie, the scFv fusion partner) to the tumor cell. In this illustrative embodiment, BLINCYTO® (blinatumomab; Amgen) is subsequently administered to target T cells to CD19 (which binds to the tumor cell). In some embodiments, a constitutive expression construct encodes an Fc-based construct or fusion protein described herein that includes an antigen-binding protein (which targets a B cell antigen) fused to CD19, or a portion. In some embodiments, a constitutive expression construct encodes a B cell-specific antibody (or part thereof) / CD19 fusion protein, or a CD19 / B cell-specific antibody (or part) fusion protein. An antigen-binding protein (eg, B cell-specific antibody) can bind to any known B cell antigen, e.g. eg, an antigen described herein (eg, CD19, CD20, CD21, CD22, CD72, CD79a, CD79b, BCMA, or CD180). In some embodiments, a constitutive expression construct encodes a scFv / CD19 fusion protein, e.g. eg, an anti-CD20 scFv / CD19 fusion protein or an anti-CD20 scFv / CD19 fragment fusion protein. In some embodiments, a constitutive expression construct encodes a CD19 / scFv fusion protein, e.g. eg, a CD19 / anti-CD20 scFv fusion protein, or a CD19 fragment / anti-CD20 scFv fusion protein. In some embodiments, a constitutive expression construct encodes an Fc-based construct or fusion protein described herein that includes an antigen-binding protein (which targets a B cell antigen) fused to an antigen or cell part. B. In some embodiments, a constitutive expression construct encodes a B cell-specific antibody (or part thereof) / B cell antigen (or part) of the fusion protein, or a B cell antigen (or part) / B cell specific antibody fusion protein (or part). In some embodiments, a constitutive expression construct encodes a fusion protein that includes (i) CD22 or part (eg, one or more of domains 1-3), CD79 or part (eg, CD79a or CD79b), and (ii) a B cell-specific antibody or part (eg, an ari-CD19, CD20, CD21, CD22, CD72, CD79a, CD79b, BCMA, or CD180 scFv). In some embodiments, a constitutive expression construct encodes a fusion protein or Fe-based construct described herein that includes an antigen-binding protein (which targets a B cell antigen) fused to CD20 (or a part). In some embodiments, a constitutive expression construct encodes a fusion protein that includes a B cell-specific antibody (or a part thereof) and CD20 (or a part). In some embodiments, a constitutive expression construct encodes a fusion protein that includes a B cell-specific antibody (or a portion thereof) and a portion of CD20 that is or includes an epitope of CD20 (as described, e.g. ., in Natarajan et al., Clin. Cancer Res. 19:6820-9 (2013)). In some embodiments, a constitutive expression construct encodes an Fc-based construct or fusion protein described herein that includes an antigen-binding protein (which targets a TSA or TAA) and CD19 or part. In some embodiments, a constitutive expression construct encodes an anti-TSA antibody (or part thereof) / CD19 fusion protein, or CD19 antibody / anti-TSA fusion protein (or part thereof). An anti-TSA antibody can bind to any known TSA, e.g. eg, any TSA described herein. In some embodiments, a TSA is a splice variant of EGFRvIII. In some embodiments, a constitutive expression construct encodes a scFv / CD19 fusion protein, e.g. eg, an anti-EGFRvIII scFv / CD19 fusion protein or an anti-EGFRvIII scFv / CD19 fragment fusion protein. In some embodiments, a constitutive expression construct encodes a CD19 / scFv fusion protein, e.g. eg, an anti-EGFRvIII CD19 / scFv fusion protein, or a CD19 fragment / anti-EGFRvIII scFv fusion protein. In some embodiments, a constitutive expression construct encodes an Fc-based construct or fusion protein described herein that includes an antigen-binding protein (which targets a TSA or TAA) and a B cell antigen or part. In some embodiments, a constitutive expression construct encodes an anti-TSA antibody (or part thereof) / B cell antigen fusion protein, or a B cell antigen / anti-TSA antibody. An antigen-binding protein (eg, anti-TSA antibody) can bind to any known TSA, e.g. eg, any TSA described herein. In some embodiments, a TSA is a splice variant of EGFRvIII. In some embodiments, a constitutive expression construct encodes a fusion protein that includes (i) an anti-EGFRvIII scFv and (ii) a B cell antigen or portion (eg, CD20 or portion (eg, CD20). , an epitope as described, eg, in Natarajan et al., Clin. Cancer Res. 19: 6820-9 (2013), CD22 or part (eg, one or more of domains 1 -3), CD79 or part (eg, CD79a or CD79b)). In some embodiments, a constitutive expression construct encodes one or more antibodies (or fragments) described herein. In some embodiments, an inducible expression construct encodes one or more antibodies (or fragments) described herein. memory. In some embodiments, an antibody described herein, as encoded by an expression construct, may be additionally or alternatively produced and / or purified using known methods. In some embodiments, such a produced and / or purified antibody, as described herein, can be used as a proteinaceous therapeutic. 3. Expressed Cytokines In some embodiments, an expression construct described herein (eg, a constitutive expression construct or inducible expression construct) encodes one or more cytokines, e.g. g., one or more cytokines known in the art, e.g. eg, used in cancer therapy. In some embodiments, an expression construct that encodes one or more cytokines is an inducible expression construct. In some embodiments, an expression construct that encodes one or more cytokines is a constitutive expression construct. Illustrative non-limiting cytokines that can be included in an expression construct include, e.g. g., IFNa, IFNP, IFNγ, IL-1, IL-2, IL-7, IL-12, IL-15, IL-21, IL-36, TNF, LTa, GM-CSF, and G-CSF. Cytokines participate in immune responses by acting through various mechanisms, including the recruitment of T cells to a tumor. Nucleotide sequences encoding cytokines, and said nucleotide sequence may be from any animal such as human, monkey, rat, mouse, hamster, dog or cat. Known problems associated with cytokine therapy include, e.g. eg, high dose requirements, toxicity, and limited efficacy. Thus, in some embodiments, an expression construct described herein is used to deliver one or more cytokines at a specific site and / or at a specific dose (eg, to reduce or eliminate one or more risks associated with cytokine therapy). In some embodiments, an expression construct includes a promoter operably linked to a gene encoding a cytokine, and the promoter mediates rapid, sustained expression. In some embodiments, an expression construct includes a promoter operably linked to a gene encoding a cytokine, and the promoter mediates delayed, late-inducible expression. In some embodiments, an expression construct includes a promoter operably linked to a gene encoding a cytokine, and the promoter mediates rapid and transient expression. In some embodiments, expression of a cytokine (eg, an immunostimulatory cytokine) on or near a surface of a tumor induces an immune response to the tumor. In some embodiments, an expressed cytokine may be a target for one or more additional cellular therapeutic agents (eg, one or more additional CAR-T cells). In some embodiments, expression of a cytokine near a surface of a tumor induces a immune response to the tumor and is also used as a target for one or more additional cellular therapeutic agents (eg, one or more additional CAR-T cells). For example, IL-21 release can be used to induce effector expansion and / or differentiation of CD8+ T cells and / or support NK cell activation and cytolytic activity. In an illustrative method, a cellular therapeutic agent includes an expression construct that includes a CD69 promoter and a nucleic acid encoding IL-21. In some embodiments, upon binding of an antigen to a tumor cell, a cellular therapeutic agent described herein exhibits sustained release of IL-21. In some embodiments, IL-21 is constitutively expressed by the cellular therapeutic agent following administration of the cellular therapeutic agent to a subject. Illustrative cellular therapeutic agents include, e.g. eg, CAR-T cells, CAR-NK cells, TCR-T cells, TIL cells, allogeneic NK cells, and autologous NK cells. In another illustrative method, IL-15 release can be used to support NK cell expansion and / or to recruit NK cells to promote an antitumor response. Figure 8 depicts an illustrative cellular therapeutic agent including an inducible expression construct that includes a TNF promoter and a nucleic acid encoding IL-15. Upon binding of an antigen to a tumor cell, the cellular therapeutic agent exhibits secretion (eg, rapid secretion) of IL-15. Illustrative cellular therapeutic agents include, e.g. eg, CAR-T cells, CAR-NK cells, TCR-T cells, TIL cells, allogeneic NK cells, and autologous NK cells. In some embodiments, one or more cytokines encoded by an expression construct bind to cells with high affinity (eg, KD of approximately 10' 7 , 10‘ 8 , 10’ 9 , 1O' 10 ,10' 11 or less) and / or have low internalization rates (eg, less than about 10, 10 2 , 10 3 , 10 4 or 10 5 cytokine molecules per cell per day). The binding affinity and internalization rates of various cytokines are known in the art and / or can be measured using known methods. In some embodiments, an expression construct described herein (eg, a constitutive expression construct or inducible expression construct) encodes a cytokine fusion protein, e.g. eg, a fusion protein of a cytokine (eg, an anti-tumor cytokine) and a target for one or more additional cellular therapeutic agents described herein (eg, a CAR-T target). Such an expression construct can provide both a target for one or more additional cellular therapeutic agents (eg, a CAR-T target) and a stimulatory cytokine on a tumor surface. For example, an expression construct may encode a cytokine-CD19 fusion protein, or a fusion of a cytokine and a CD19 fragment, e.g. eg, a fragment of CD19 to which a CD19-CAR-T cell binds. In some embodiments, a CD19 fragment is an IgC domain of CD19. Without Wishing to be bound by theory, a single expression construct encoding such a fusion protein advantageously allows a cellular therapeutic agent to be genetically engineered using (eg, a single) minimal transgene. In some embodiments, a non-inducible expression construct encodes one or more of the cytokines or cytokine fusion proteins described herein. In some embodiments, an inducible expression construct encodes one or more of the cytokines or cytokine fusion proteins described herein. In some embodiments, a cytokine fusion protein described herein, as encoded by an expression construct, may additionally or alternatively be produced and / or purified using known methods. In some embodiments, such a produced and / or purified fusion protein, as described herein, can be used as a protein therapeutic. 4. Expressed Scaffold Fusion Proteins In some embodiments, an expression construct described herein (eg, a constitutive expression construct or inducible expression construct) encodes a fusion protein comprising a scaffold polypeptide (or fragment thereof) and a target for one or more additional cellular therapeutic agents described herein (eg, a CAR-T target). A scaffold polypeptide (or fragment) can be selected for attachment, e.g. eg, to a tumor antigen (eg, a tumor antigen described herein). Such scaffold polypeptides (or fragments) include, e.g. eg, a fibronectin domain (eg, a Type III fibronectin domain), a DARPin, an adhiron, a lipocalin / anticalin, a protein A, an affibody, a thioredoxin, etc. For example, an expression construct may encode a fibronectin Type III domain-CD19 fusion protein, or a fusion of a fibronectin Type III domain and a CD19 fragment, e.g. eg, a CD19 fragment to which a CD19-CAR-T cell binds. In some embodiments, a CD19 fragment is an IgC domain of CD19. In some embodiments, a constitutive expression construct encodes one or more scaffold fusion proteins described herein. In some embodiments, an inducible expression construct encodes one or more scaffold fusion proteins described herein. In some embodiments, a scaffold fusion protein described herein may be additionally or alternatively produced and / or purified using known methods. In some embodiments, such a produced and / or purified scaffold fusion protein, as described herein, can be used as a protein therapeutic. 5. CD19 as a Scaffold for Expressed CD19 Variant Proteins and CD19 Variant Fusion Proteins CD19 is a 95 kd transmembrane glycoprotein that belongs to the Ig superfamily and includes two extracellular C2-type Ig domains (see, e.g., Tedder Nature Rev. Rheum. 5:572-577 (2009); Wang et al., Exp. Hematol. Oncol. Nov 29 2012;l(l):36.doi:10.1186 / 2162-3619-1-36.)). In some embodiments, the extracellular domain (ECD) of CD19, and / or one or both of the C2-type Ig domains are used as scaffolds for mutagenesis, and CD19 variants (eg, CD19 or a part of which includes one or more mutations within the ECD and / or one or both C2-type Ig domains) can be screened and selected for binding to a target antigen described herein. The nucleotide sequence of human CD19 is known (see Genbank Accession No. M84371.1). To provide variant nucleic acid sequences encoding CD19 variants that bind a particular antigen, a number of methods known in the art can be used. In some embodiments, a screening method is used that allows identification and / or isolation of nucleic acids encoding CD19 variants that bind a particular antigen. Illustrative methods include a so-called bioadsorption step, known from technologies such as phage display (Kang, A.S. et al. 1991. Proc Natl Acad Sci USA 88, 4363-4366), ribosome display (Schaffitzel, C. et al. 1999. J. Immunol. Methods 231, 119-135), DNA display (Cull, M. G. et al. 1992. Proc Nati Acad Sci USA 89, 1865-1869), RNA peptide display (Roberts, R. W., Szostak, J. W., 1997. Proc Nati Acad Sci USA 94, 12297-12302), covalent display (WO 98 / 37186), bacterial surface display (Fuchs, P. et al. 1991. Biotechnology 9, 1369-1372), display of yeast surfaces (Boder, E. T., Wittrup, K. D., 1997. Nat Biotechnol 15, 553-557) and presentation of eukaryotic viruses (Grabherr, R., Ernst, W., 2001. Comb. Chem. High Throughput. Screen 4, 185-192). FACS and magnetic bead sorting are also applicable for enrichment (adsorption) purposes using labeled antigen. Immunodetection assays such as ELISA (Dreher, M. L. et al. 1991. J. Immunol. Methods 139, 197-205) and ELISPOT (Czerkinsky, C. C. et. al. 1983. J Immunol Methods. 65, 109-21) are also used. they can be used either after an adsorption step or alone. Thus, in some embodiments, an expression construct described herein (eg, a constitutive expression construct or inducible expression construct) encodes a variant (or fragment) of CD19, either alone or as part of a protein. melting described herein. For example, an expression construct described herein may encode a variant (or fragment) of CD19 selected to bind to a tumor agent and which, upon expression, may bind to tumor antigen and which itself may be a target for an additional cellular therapeutic agent (eg, a CD19-binding CAR-T cell). In some embodiments, a CD19 variant (or fragment) may comprise one or more mutations, relative to wild-type CD19, within the ECD and / or one or both Ig domains. In some embodiments, an expression construct described herein encodes a CD19 variant that includes an ECD variant or a C2-like Ig domain variant selected for binding to a tumor antigen. Upon expression of the CD19 variant, the ECD domain or C2-type Ig domain binds to tumor antigen on a tumor cell. Subsequently, treatment with (eg, administration to a subject of) a CD19-recognizing CAR-T cell kills the tumor cell to which the CD19 variant binds. An example of such a CD19 variant is depicted in Figure 12A. In some embodiments, an expression construct described herein encodes a CD19 variant that includes variants of both C2-type Ig domains, each of which is selected to bind a tumor antigen (eg, different epitopes of the tumor antigen). Upon expression of the CD19 variant, the C2-type Ig domain binds to tumor antigen on a tumor cell. Subsequently, treatment with (eg, administration to a subject of) a CD19-recognizing CAR-T cell kills the tumor cell to which the CD19 variant binds. An example of such a CD19 variant is depicted in Figure 12B. In some embodiments, a CD19 variant selected to bind to a target antigen is included in a fusion protein. For example, a CD19 variant that includes an ECD variant or a C2-type Ig domain variant selected for binding to tumor antigen can be fused to an antibody or fragment thereof that also binds to tumor antigen (eg. g., to a different epitope on the tumor antigen). Illustrative fusion proteins include, e.g. eg, CD19 variant / scFv fusion proteins and CD19 / VHH variant fusion proteins. An expression construct described herein may encode a CD19 variant / antibody fusion protein and, upon expression, the CD19 variant and the fusion protein antibody bind to tumor antigen on a tumor cell. Subsequently, treatment with (eg, administration to a subject of) a CAR-T cell that recognizes CD19 kills the tumor cell to which the CD19 variant / antibody fusion protein binds. An example of such a CD19 variant is depicted in Figure 12C. In some embodiments, a constitutive expression construct encodes one or more CD19 variant proteins or CD19 variant fusion proteins described herein. In some embodiments, an inducible expression construct encodes one or more CD19 variant proteins or CD19 variant fusion proteins described herein. In some embodiments, a CD19 variant protein or CD19 variant fusion protein described herein may be additionally or alternatively produced and / or purified using known methods. In some embodiments, a purified CD19 variant protein or CD19 variant fusion protein, as described herein, can be used as a proteinaceous therapeutic. Additional non-limiting examples of fusion proteins that include CD19 variants (or fragment) as a scaffold include, e.g. eg, CD19 variant / cytokine fusion proteins and CD19 variant / TLR agonist fusion proteins 6. Specific Markers of B Cells and Additional Proteins as Scaffolds In addition to CD19, other B-cell-specific markers belonging to the Ig superfamily can also be used as scaffolds for mutagenesis, and B-cell-specific marker variants can be screened and selected to bind to a target antigen described herein. memory. In some embodiments, a specific marker for B cells is CD19, CD20, CD21, CD22, CD23, CD24, CD40, CD72, CD180, ROR1, BCMA, CD79a, or CD79b (see, e.g., LeBien et al., Blood 112:1570-1580 (2008)). For example, CD22 contains 7 Ig domains, each of which can be mutated individually or in combination with one or more of the other CD22 Ig domains and screened using the methods described herein for binding to tumor antigen. In some embodiments, a CD22 variant or fragment includes the first 1, 2, 3, 4, 5, 6, or all 7 Ig domains (eg, domains 1-3). In some embodiments, a CD22 variant (or fragment) may comprise one or more mutations, relative to wild-type CD22, within each of one or more Ig domains of CD22 (eg, domains 1 and 2). of CD22 or domains 1 to 3 of CD22, etc.). Thus, in some embodiments, an expression construct described herein encodes a variant (or fragment) of CD22, either alone or as part of a fusion protein described herein. For example, an expression construct described herein may encode a CD22 variant (or fragment) selected to bind to a tumor agent and which, upon expression, may bind to tumor antigen and which itself may be a target for an additional cellular therapeutic agent (eg, a CAR-T cell that binds CD22). Similarly, CD79a and CD79b each consist of a single Ig domain, each of which can be mutated and screened using the methods described herein to bind a tumor antigen. Thus, in some embodiments, an inducible expression construct described herein encodes a variant of CD79a or CD79b, either alone or as part of a fusion protein described herein. For example, an expression construct described herein may encode a CD79 variant selected to bind to a tumor agent and which, upon expression, may bind to tumor antigen and itself may be a target for a cellular therapeutic agent. (eg, a CAR-T cell that binds CD79a or CD79b). Additional B cell-specific proteins that can be used as a scaffold as described herein include the C-type lectins CD23 and CD72 (see, e.g., LeBien et al., Blood 112:1570-1580 (2008 )). As precedent, another C-type lectin tetranectin (see, eg, Byla et al. JBC 285: 12096-12100 (2010)) has been used successfully as a scaffold protein. Accordingly, in some embodiments, an expression construct described herein encodes a variant (or fragment) of CD23 or CD72, either alone or as part of a fusion protein described herein. For example, an expression construct described herein may encode a fusion protein that comprises a variant (or fragment) of CD23 or CD72 selected to bind to a tumor antigen and which, upon expression, is capable of binding to the tumor antigen. The fusion protein may further comprise a polypeptide target for an additional cellular therapeutic agent (eg, a CAR-T cell that binds to the polypeptide target). 7, Toxins Expressed In some embodiments, an expression construct described herein (eg, a constitutive expression construct or inducible expression construct) encodes one or more toxins. In some of these embodiments, an expression construct is designed so as to control the timing of expression of the encoded toxin (eg, production of a "smart bomb" cellular therapeutic agent). For example, an expression construct may include a promoter appropriate to mediate delayed expression of an encoded toxin (eg, a VLA1 promoter), or an expression construct may include a promoter appropriate to mediate rapid expression and / or transient (eg, a TNF promoter)). A nucleotide sequence encoding any known protein toxin may be included in an inducible expression construct, e.g. eg, bacterial toxins such as diphtheria toxin and plant toxins such as ricin. Additional enzymatically active toxins and fragments thereof that can be used include diphtheria A chain, diphtheria toxin non-binding active fragments, anthrax toxin, shiga toxin, exotoxin A chain (from Pseudomonas aeruginosa) , ricin A chain, abrin A chain, modeccin A chain, alpha-sarcin, Aleurites fordii proteins, diantin proteins, Phytolaca americana proteins (PAPI, PAPII and PAP-S), momordica charanda inhibitor, curcin, cretin, sapaonaria officinalis inhibitor, gelonin, mitogelin, restricted na, phenomycin, enomycin, and the trichotrecenes. See, for example, WO 93 / 21232. In some embodiments, expression and / or delivery of a toxin to a target cell is controlled by administering or contacting a target cell with a defined number of cellular therapeutic cells that include an expression construct encoding a toxin. For example, a population of cellular therapeutic cells can be administered to a subject and / or contacted with a target cell. In some embodiments, said population includes a list of cellular therapeutic cells including, for example, an expression construct and cellular therapeutic cells that do not include an expression construct. For example, a population having a ratio of expression construct-containing therapeutic cell cells and therapeutic cell cells lacking an expression construct of about 1:10,1:100,1:1000, 1:10000 can be administered. ,1:100000, or more. In some embodiments, delivery of a toxin by a cellular therapeutic agent induced to express a toxin can kill, e.g. eg, 10, 50, 100, 250, 500, 750, 1000, 1500, 2000 or more cells in close proximity to the target cell. In some embodiments, an expression construct may include a "kill switch" in tandem with the nucleic acid encoding a toxin, thereby stopping expression of the toxin by the cellular therapeutic agent after a defined period of time. (eg, after 1, 2, 4, 8, 12 hours, or more). Safety "switches" can be used to turn off cellular therapeutic agents, e.g. eg, when they cause life-threatening inflammation or attack normal healthy tissue. For example, such a "switch" can induce caspase 9-dependent apoptosis when a CAR-T cell is exposed to rimiducid (a pill that can be given to patients if they develop life-threatening side effects; Bellicum Pharmaceuticals Inc. .). Many of these switches are known in the context of the present disclosure and may be used in the preclinical and clinical development of the present disclosure (see, eg, Tey, 2014. Adoptive T-cell therapy: adverse events and safety switches. Clinical & Translational Immunology 3, el7; doi:10.1038 / cti.2014.11). Figure 10 depicts an illustrative cellular therapeutic agent encoding an inducibly expressed toxin (eg, diphtheria toxin, anthrax toxin, shiga toxin). As shown in Figure 10, a cellular therapeutic agent includes an antigen-binding receptor on its surface, which includes an antigen-binding domain (eg, an antigen-binding domain described herein) and a signaling domain (eg, a signaling domain described herein). The cellular therapeutic agent also includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes diphtheria toxin. Upon binding of the antigen-binding domain to a first antigen on a tumor cell, the signaling domain induces expression of diphtheria toxin, leading to cell death. 8. Other Genes Expressed In some embodiments, an expression construct (eg, a constitutive expression construct or inducible expression construct) encodes an agent that targets the microenvironment of a tumor. The microenvironment of certain cancers and / or tumors is known to provide tumor protection against cellular therapeutic attack. For example, Such protective microenvironments may include an extracellular matrix (ECM) that prevents or reduces the efficiency of cellular attack, may include hypoxic and / or acidic pH conditions, and / or may include immunosuppressive signals. In some embodiments, an expression construct encodes a protein that targets and / or mediates degradation of a tumor microenvironment. Such proteins are known in the art. For example, an expression construct may encode a hyaluronidase, a heparinase, a matrix metalloproteinase (MMP), and / or an ADAM (a disintegrin and metalloproteinase, eg, ADAMsl-20, eg, ADAM8, ADAM10, ADAM17) (see, e.g., Edwards et al., Mol. Aspects Med. 29:258-89 (2008); Decock et al., J. Cell. Mol. Med. 15:1254-65 ( 2011); McAtee et al., Adv. Cancer Res. 123:1-34 (2014); Stanton et al., Biochim. Biophys. Acta 1812:1616-1629 (2011)). Figure 11 depicts an illustrative cellular therapeutic agent which encodes inducibly expressed genes. As shown in Figure 11, a cellular therapeutic agent includes an antigen-binding receptor on its surface, which includes an antigen-binding domain (eg, an antigen-binding domain described herein) and a signaling domain (eg, a signaling domain described herein). The cellular therapeutic agent also includes an inducible expression construct (eg, an inducible expression construct described herein), which encodes a gene (eg, a gene depicted in Figure 11). Upon binding of the antigen-binding domain to an antigen on a tumor cell, the signaling domain induces expression of the gene. In some embodiments, an inducible expression construct encodes factors for T cell and / or NK cell function and / or survival (eg, leukocyte expansion molecule (LEM); see, eg, Leavy, Nat Rev Immunol 15:334 (2015)). 9. Fusion Proteins Expressed with Cleavage Linkers In some embodiments, any of the fusion proteins described herein (eg, an scFv-CD19 fusion protein) can include a linker between fusion partners. A variety of linkers and suitable methods for preparing fusion proteins including linkers are known in the art. The linker may be cleavable, e.g. g., under physiological conditions, e.g. eg, under intracellular conditions, such that cleavage of the linker releases the fusion partners. The linker may be, for example, a peptidyl cleavage linker, e.g. eg, by a plasma peptidase or protease enzyme, including, but not limited to aminopeptidase, plasmin, and quinine-kallikrein. In some embodiments, the linker can be cleaved by a tumor-associated protease, e.g. matriptase, Cathepsin B. In some embodiments, cleavage by a tumor-associated protease induces a conformational change in CD19, allowing binding and / or expression of the epitope of CAR to allow extermination. In some embodiments, the peptidyl linker is at least two amino acids long or at least three amino acids long. 10. Constructions based on Expressed Faith In some embodiments, an expression construct described herein (eg, a constitutive expression construct or inducible expression construct) encodes an Fe-based construct. In some embodiments, an Fe-based construct is a fusion protein CD19-Fc, e.g. eg, a construct depicted in Figure 52A. As shown in Figure 52A, a CD19-Fc fusion protein can be a dimer of two monomers, each of which includes all or part of an antibody heavy chain Fc region fused to a form containing an extracellular C2-type Ig domain of CD19. In some embodiments, a CD19-Fc fusion protein includes an ECD variant or one or two C2-like Ig domain variants described herein. In some embodiments, one or both of the extracellular Ig-type C2 domains of CD19 are variants of the Ig-type C2 domain described herein. In the illustrative embodiment depicted in Figure 51A, both Ig-type C2 domains are Ig-type C2 domain variants (represented with "**"). In some embodiments, such a construct binds both a tumor antigen (eg, a TSA or TAA described herein) through one or both of the C2-type Ig domain variants (or C2 domain variant). of ECD), and presents CD19 as a target for one or more additional therapeutic agents described herein (eg, CART, ADC, etc.). In some embodiments, an Fe-based construct is schematically depicted in Figure 51B, where the construct is a CD19-scFv-Fc fusion protein. As shown in Figure 51B, an illustrative construct is a heterodimer, where a monomer includes all or part of an antibody heavy chain Fc region fused to an scFv (eg, an scFv described herein). memory), and a monomer includes all or part of a heavy chain Fc region of an antibody fused to all or part of CD19. In some embodiments, such a construct binds to a tumor antigen (eg, a TSA or TAA described herein) via scFv, and presents CD19 as a target for one or more additional therapeutic agents described in this memory (eg, CART, ADC, etc.). In some embodiments, an Fe-based construct is the one schematically depicted in Figure 51C, where the construct is a CD19-scFv-Fc fusion protein. As shown in Figure 51C, an illustrative construct is a heterodimer, where a monomer includes all or part of an antibody heavy chain Fc region fused to an scFv (eg, an scFv described herein). memory), and a monomer includes all or part of a heavy chain Fe region fused to a C2-type Ig domain variant extracellular described herein (represented with "**"). In some embodiments, such a construct may be bivalent, in that the scFv and C2-type Ig domain variant (or ECD variant) that bind to the same target (eg, a TSA or TAA described herein), or can be bispecific, in that the domain variant of scFv and Ig of type C2 (eg, TSA or TAA described herein). Furthermore, such a construct presents CD19 as a target for one or more additional therapeutic agents described herein (eg, CART, ADC, etc.). In some embodiments, an Fe-based construct is or includes a bispecific antibody, or part thereof, that binds to different targets (eg, a TSA or TAA described herein). Various bispecific antibodies are known in the art (see, e.g., Kontermann et al. Drug Disc. Today 20:838-847 (2015); Spiess et al., Mol. Immunol. 67:95-106 (2015) ), and can be used in a construct described herein. Illustrative bispecific antibodies include, e.g. e.g., trioab, button-in-hole (kih) IgG, crossMab, ortho-Fab IgG, dual variable domain immunoglobulins (DVD-Ig), 2-in-1-IgG, IgG-scFv, tandem scFv, scFv 2-Fc, bi-nanobody, BiTE, tandAbs, DART, DART-Fc, scFv-HAS-scFv, dock-and-lock (DNL)-Fab3, ImmTAC, DAF, HAS-body, IgG finomer, and ART-Ig. Additional examples include XmAb5574, XmAb5871, XmAb7195, Xtend-TNF, XmAbl4045, XmAbl3676, XmAbl3551 (Xencor). An illustrative construct that includes heterodimeric heavy chains is depicted in Figure 52A, and in which one arm of the construct includes a VH / VL and the other arm includes an scFv fused to the Fe region. In some embodiments, a construct depicted in FIG. Figure 52A is monovalent, in that the VH / VL arm binds a tumor antigen (eg, a TSA or TAA described herein), and the scFv binds a T cell antigen described herein. (eg, CD3). Another illustrative construct is depicted in Figure 52B, in which the scFv of the construct depicted in Figure 52A is replaced by one or two extracellular C2-like Ig domains from CD19. In addition, the construct depicted in Figure 52B features CD19 as a target for one or more additional therapeutic agents described herein (eg, CART, ADC, etc.). Another illustrative construct is depicted in Figure 52C, in which one or both of the CD19 extracellular Ig-type C2 domains are variants of the Ig-type C2 domain described herein (represented by "**"). In some embodiments, such a construct may be bivalent, in that the VH / VL and C2-type Ig domain variant (or ECD variant) bind to the same target (e.g., a TSA or TAA described herein), or it can be bispecific, in that the VH / VL and C2-like Ig domain variant (or ECD variant) bind to different targets (e.g., a TSA or TAA described in this memory). Furthermore, such a construct depicted in Figure 53C presents CD19 as a target for one or more additional therapeutic agents described herein (eg, CART, ADC, etc.). In some embodiments, an Fe-based construct includes an Fc-Ig "swap." Figure 53A schematically depicts an antibody in which each of the Fe heavy chains includes two Ig constant domains, one designated CH2 (blue) and the other designated CH3 (red). In some embodiments, an Fe-based construct includes an antibody as depicted in Figure 53B, which includes one or two heavy chains including CH2 (blue) fused to one or more CD19 extracellular C2-like Ig domains described herein. specification, one or more CD22 Ig domains described herein and / or one or more CD79a or CD79b Ig domains described herein (represented in green in Figure 53B). In some embodiments, an Fe-based construct includes a fusion protein (as described herein) and includes an Ig constant domain, or a Type III fibronectin domain, and one or more "loops" of a CD19 extracellular C2-like Ig domain described herein. The structure of the extracellular C2-type Ig domains of CD19 is known to include three "loops". An illustrative construct is depicted in Figure 54A, in which a loop in one or both Fe CH3 domains is replaced by a loop from the CD19 extracellular C2-like Ig domain. Another illustrative construct is depicted in Figure 54B, in which 1, 2 or 3 loops of the extracellular type C2 Ig domain of CD19 are grafted onto VH, Type III fibronectin domain or scFv. In some embodiments, a constitutive expression construct encodes one or more Fe-based constructs described herein. In some embodiments, an inducible expression construct encodes one or more Fe-based constructs described herein. In some embodiments, an Fe-based construct described herein may be additionally or alternatively produced and / or purified using known methods. In some embodiments, such produced and / or purified Fe-based constructs, as described herein, can be used as a protein therapeutic. 11. Expressed Polyeptides with Inducible Function In some embodiments, an expression construct described herein (eg, a constitutive expression construct or inducible expression construct) encodes one or more polypeptides, which exhibit one or more inducible functions. In some embodiments, a polypeptide is or comprises, e.g. eg, an antibody or enzyme, one or more functions of which are reversibly reduced, blocked or inhibited, and whose function can be induced, e.g. e.g., by unlocking or disinhibition. A variety of polypeptides with inducible function are known in the art and include, e.g. eg, polypeptides that include ligand-binding sites (eg, inducible hormone-binding domain function (see, eg, Eilers et al Nature 340, 66-68 1989) or masked polypeptides (eg, antibodies, enzymes). In some embodiments, an inducible function is the inducible binding of a target antigen (eg, a TAA or TSA described herein). Masked Constructions In some embodiments, an expressed polypeptide is or includes a masked version of an antigen-binding protein described herein (eg, antibody or antibody fragment described herein, or a scaffold protein described herein ( eg, Type III fibronectin domain, CD19 variant protein, or B-cell specific marker variant described herein)). In some embodiments, an expressed polypeptide includes a masked version of an antibody or antibody fragment described herein (eg, a Probody® as described, eg, in Sandersjoo et al. Cell. Mol Life Sci. (2015) 72:1405-1415; US 2015 / 0183875; US 8,513,390; and US 9,120,853). In some embodiments, a masked construct comprises an antibody, or fragment thereof, or a scaffold protein described herein (eg, the Type III fibronectin domain, CD19 variant protein, or specific marker variant for B cells described herein), a masking moiety, a cleavable moiety, and / or a linker. In some embodiments, a masked construct includes an antigen-binding protein that targets one or more of the TSAs described herein. In some embodiments, a masked construct includes an antigen-binding protein that targets one or more TAAs described herein. In some embodiments, a masked construct includes an antigen-binding protein, which targets one or more TSAs and one or more TAAs described herein. In some embodiments, an induced expression construct encodes one or more masked constructs. In some embodiments, a constitutive expression construct encodes one or more masked constructs. In some embodiments, a masked construct comprises an antigen-binding protein (eg, antibody, or fragment thereof, or a scaffold protein described herein (eg, fibronectin Type III domain, variant protein CD19, or B-cell-specific marker variant described herein), and a masking moiety. In some embodiments, a masking moiety is an amino acid sequence coupled to the antigen-binding protein, and positioned in such a manner which reduces the ability of the protein to specifically bind to its target ("masking" the antigen-binding protein).In some embodiments, a masking moiety is coupled to the antigen-binding protein via a linker.In some embodiments, a masking moiety is coupled to the antigen-binding protein via a linker. embodiments, the specific binding of a masked antigen-binding protein to its target is reduced or inhibited, compared to the specific binding of an "unmasked" antigen-binding protein, or and n comparison with the specific binding of the precursor antigen-binding protein, to the target. In some embodiments, a masked antigen-binding protein demonstrates no measurable binding or substantially no measurable binding to the target, and / or demonstrates no more than 0.001%, 0.01%, 0.1%, 1%, 2%, 3% , 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, or 50% binding to target, compared with the binding of an unmasked antigen-binding protein, or in comparison with the binding of the precursor antigen-binding protein to the target, e.g. g., for at least 2, 4, 6, 8, 12, 28, 24, 30, 36, 48, 60, 72, 84, 96 hours, or 5, 10, 15, 30, 45, 60, 90, 120, 150, 180 days, or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 months or more, e.g. eg, when measured in vivo or in an in vitro Target Displacement immunosorbent assay (described in US 8,513,390). In some embodiments, the specific binding of a masked antigen-binding protein to its target is reduced or inhibited, as compared to the specific binding of the unmasked antigen-binding protein, or as compared to the specific binding of the unmasked antigen-binding protein. binding of precursor antigen to the target. The Kd of the masked antigen binding protein towards the target can be at least 5, 10, 25, 50, 100, 250, 500, 1,000, 2,500, 5,000, 10,000, 50,000, 100,000, 500,000, 1,000,000, 5,000, 5,000,000 , 50,000,000 or greater, or between 5-10, 10-100, 10-1,000, 10-10,000, 10-100,000, 10-1,000,000, 10-10,000,000, 100-1,000, 100-10,000, 10,000-0100 , 100-10,000,000, 1,000-10,000, 1,000-100,000, 1,000-1,000,000, 1000-10,000,000, 10,000-100,000, 10,000-1,000,000, 10,000-10,000,000, 100,000-1,000,000, or 100,000-10,000,000 times greater than the protein of union to antigen unmasked or than the precursor antigen-binding protein. Conversely, the binding affinity of the masked antigen-binding protein towards the target can be at least 5, 10, 25, 50, 100, 250, 500, 1,000, 2,500, 5,000, 10,000, 50,000, 100,000, 500,000 , 1,000,000, 5,000,000, 10,000,000, 50,000,000 or greater, or between 5-10, 10-100, 10-1,000, 10-10,000, 10-100,000, 10-1,000,000, 10-10,000,000, 100-1,000, 100-10,000, 100, 100, 100, 100 -100,000, 100-1,000,000, 100-10,000,000, 1,000-10,000, 1,000-100,000, 1,000-1,000,000, 1000-10,000,000, 10,000-100,000, 10,000-1,000,000, 10,000-10,000,000, 100,000-1,000,000 or 100,000-10,000,000 less than protein unmasked antigen-binding protein or than the precursor antigen-binding protein. Masking moieties are known in the art and include, e.g. eg, known binding partners of antibodies, or fragments thereof. In some embodiments, a masking moiety is an amino acid sequence at the N-terminus, C-terminus, and / or within an internal site (eg, an antigen-binding loop) of the antigen-binding protein. . In some embodiments, a masking moiety is or includes one or more pairs of cysteine ​​residues, e.g. g., resulting in the formation of a disulfide bond between cysteine ​​pairs. In some of these embodiments, the disulfide bonds result in a conformationally constrained structure, which can be "unmasked" by cleavage of the disulfide bond, e.g. eg, by a reducing agent. Illustrative masking moieties are described in, p. eg, Sanersjoo et al. Cell. Mol. Life Sci. (2015) 72:1405-1415; US 2015 / 0183875; US 8,513,390; and US 9,120,853. In some embodiments, an expressed polypeptide is an antibody fusion protein described herein that includes a masking moiety, e.g. eg, a masked scFv-CD19 or masked CD19-scFv fusion protein described herein. In some embodiments, a masked scFv-CD19 fusion protein includes a masking moiety at the N-terminus of the fusion protein. In some embodiments, a masked scFv-CD19 fusion protein includes a masking moiety at the C-terminus of the fusion protein. In some embodiments, a masked CD19-scFv fusion protein includes a masking moiety at the N-terminus of the fusion protein. In some embodiments, a masked CD19-scFv fusion protein includes a masking moiety at the C-terminus of the fusion protein. In some embodiments, an expressed polypeptide is a masked fusion protein that includes an scFv described herein at the N-terminus and a CD19 fragment at the C-terminus (an scFv fragment-CD19 fusion protein), or a CD19 fragment protein. masked fusion including a CD19 fragment at the N-terminus and a scFv described herein at the C-terminus (a CD19 scFv fragment fusion protein). In some embodiments, a masked scFv-CD19 fragment fusion protein includes a masking moiety at the N-terminus of the fusion protein. In some embodiments, a masked scFv-CD19 fragment fusion protein includes a masking moiety at the C-terminus of the fusion protein. In some embodiments, a masked CD19 fragment-scFV fusion protein includes a masking moiety at the N-terminus of the fusion protein. In some embodiments, a masked CD19 fragment-scFV fusion protein includes a masking moiety at the C-terminus of the fusion protein. In some embodiments, an expressed polypeptide is or includes a masked antibody (or fragment thereof) known in the art, including but not limited to a masked version of cetuximab, panitumumab, infliximab, adalimumab, efalizumab, ipilimumab, tremelimumab, adecatumumab, Hu5c8, alemtuzumab, ranibizumab, tositumomab, ibritumomab tiuxetan, rituximab, infliximab, bevacizumab, or figitumumab, or a fragment thereof (eg, a masked scFv fragment). Additional antibodies that can be masked are described, e.g. eg, in documents US 8,513,390, US 9,120,853, US 9,127,053, US 20150183875, US 20140363430, US 20140045195, US20130101555 and US 20100189651. In some embodiments, a masked antibody or fusion protein further includes one or more cleavage moieties. In some embodiments, a cleavable moiety is or includes e.g. eg, one or more amino acid sequences that can serve as a substrate for one or more proteases such as one or more extracellular proteases. In some embodiments, a cleavage moiety is or includes a cysteine-cysteine ​​pair capable of forming a disulfide bond, which can be cleaved by the action of a reducing agent. In other embodiments, a cleavable moiety is or includes a substrate capable of being cleaved upon photolysis. In some embodiments, a cleavable moiety is selected for the presence of a protease or a protease in proximity to tissue with a desired target of an antibody, or fragment thereof. In some embodiments, the target tissue is cancerous tissue. Proteases that have substrates in a number of cancers, e.g. solid tumors, are known in the art (see, eg, La Rocca et al, (2004) British J. of Cancer 90(7):1414-1421). In some embodiments, a cleavage moiety is or includes a target for, e.g. eg, legumain, plasmin, TMPRSS-3 / 4, MMP-9, MT1-MMP, ADAM (a disintegrin and metalloproteinase, eg, ADAMsl-20, eg, ADAM8, ADAM10, ADAM17), cathepsin (eg, cathepsin A, B, C, D, E, F, G, H, L, K, O, S, V, or W (Tan et al., World J. Biol. Chem. 4: 91-101 (2013)), caspase, human neutrophil elastase, beta-secretase, matriptase, uPA, or PSA. In some embodiments, a masked construct described herein includes a linker, e.g. eg, C-terminally and / or N-terminally with a masking moiety and / or cleavage moiety. In some embodiments, a linker can provide flexibility for the masking moiety to reversibly inhibit binding of the antigen-binding protein to its target. Suitable linkers can be easily selected and can be of any of several lengths, such as 1 amino acid (eg, Gly) to 20 amino acids, 2 amino acids to 15 amino acids, 3 amino acids to 12 amino acids, including 4 amino acids. to 10 amino acids, 5 amino acids to 9 amino acids, 6 amino acids to 8 amino acids, or 7 amino acids to 8 amino acids, and can be 1, 2, 3, 4, 5, 6, or 7 amino acids. In some embodiments, a masking moiety is coupled to an antigen-binding protein via a polypeptide linker. In some embodiments, a linker used to fuse a masking moiety to an antigen-binding protein is a cleavage moiety described herein. In some embodiments a masking moiety is fused, directly or via a linker, to the N-terminus of an antigen-binding protein. In some embodiments, a masking moiety is fused, directly or via a linker, to the C-terminus of an antigen-binding protein. A masked construct can include any expressed polypeptide described herein. A set of illustrative masked constructs is depicted in Figure 56, showing fusion of a masking moiety to the constructs described in Figures 51B and 51C. In some embodiments, as depicted in Figure 55, a masking moiety can be fused to the N-terminus of the scFv. Another illustrative set of masked constructs is depicted in Figure 57, showing the fusion of a masking moiety to the constructs described in Figures 52B and 52C. In some embodiments, as depicted in Figure 56, a masking moiety may be fused to the N-terminus of the VH and / or VL in the VH / VL arm. Another illustrative set of masked constructs is depicted in Figure 57, showing the fusion of a masking moiety to the construct depicted in Figure 53B. In some embodiments, as depicted in Figure 57, a masking moiety may be fused to the N-terminus of each of the heavy chains, each including CH2 (blue) fused to one or more extracellular C2-type Ig domains. CD19 domains described herein, one or more CD22 Ig domains described herein, and / or a CD79a or CD79b Ig domain described herein (represented in green). In some embodiments, a masking moiety can be fused to the N-terminus of one or both heavy chains. Additionally or alternatively, in some embodiments, a masking moiety may be fused to the N-terminus of one or both light chains. A further illustrative masked construct is depicted in Figure 58, showing fusion of a masking moiety to the constructs described in Figures 54A and 54B. In some embodiments, as depicted in Figure 58, a masking moiety can be fused to the N-terminus of a heavy chain and / or the VH scFv. In some embodiments, a constitutive expression construct encodes one or more masked constructs described herein. In some embodiments, an inducible expression construct encodes one or more masked constructs described herein. In some embodiments, a constitutive expression construct encodes a masked construct described herein (eg, a masked construct depicted in Figure 55, 56, 57, or 58). In some embodiments, a constitutive expression construct encodes a masked fusion protein or masked Fe-based construct described herein that includes an antigen-binding protein (that targets a TSA or TAA) fused to a target for a cell. CART, an ADC, etc., described herein. In some embodiments, a constitutive expression construct encodes a masked fusion protein or masked Fe-based construct described herein that includes an antigen-binding protein (that targets a TSA or TAA) fused to a B cell antigen. or part described herein. In some embodiments, a constitutive expression construct encodes a fusion protein that includes a masked anti-TAA and / or anti-TSA antibody (or part thereof) and CD19 or fragment. A masked (when unmasked) antigen-binding protein can bind any known TAA and / or TSA, e.g. eg, any TAA and / or TSA described herein. In some embodiments, a masked construct described herein may be additionally or alternatively produced and / or purified using known methods. In some embodiments, masked and / or purified constructs of this type, as described herein, can be used as a protein therapeutic agent. Methods of Producing Cellular Therapeutic Agents In general, a cellular therapeutic agent described herein can be produced from an immune cell, e.g. eg, a cell useful in or capable of being used in adoptive cell therapy. In some embodiments, a cellular therapeutic agent is produced from a cell type selected from a group consisting of TILs, T cells, CD8 cells + , CD4 cells + NK cells, delta-gamma T cells, regulatory T cells, or peripheral blood mononuclear cells. As used herein, "tumor infiltrating lymphocytes" or TILs refer to white blood cells that have left the bloodstream and migrated into a tumor. Lymphocytes can be divided into three groups, including B cells, T cells, and natural killer cells. As used herein, "V cells" refers to CD3 cells + , including CD4 helper cells + , CD8 cytotoxic T cells + and delta-gamma T cells. In certain embodiments, a cellular therapeutic agent is produced by genetically modifying (eg, transforming) a cell, e.g. eg, an immune cell, with a nucleic acid encoding an antigen-binding receptor and / or an expression construct described herein (eg, (i) a first recombinant expression vector including a nucleic acid encoding an antigen-binding receptor and a second recombinant expression vector including an inducible expression construct (ii) a single recombinant expression vector including both an antigen-encoding nucleic acid and an antigen-binding receptor and an inducible expression construct; or (Ni) a recombinant expression vector including a constitutive expression construct). The recombinant expression vector may comprise any type of nucleotides, including, but not limited to DNA and RNA, which may be single-stranded or double-stranded, synthesized or obtained in part from natural sources, and may contain natural, non-natural nucleotides. natural or altered. A recombinant expression vector may comprise naturally occurring or non-naturally occurring internucleotide linkages, or both types of linkages. A recombinant expression vector can be any suitable recombinant expression vector. Suitable vectors include those designed for propagation and expansion or for expression or both, such as plasmids and viruses. For example, a vector can be selected from the pUC series (Fermentas Life Sciences, Glen Burnie, Md.), the pBluescript series (Stratagene, LaJolla, Calif.), the pET series (Novagen, Madison, Wis.), the pGEX series (Pharmacia Biotech, Uppsala, Sweden), and the pEX series (Clontech, Palo Alto, Calif.). Bacteriophage vectors such as AGT10, AGT11, AZapII (Stratagene), AEMBL4 and ANM1149 can also be used. Examples of plant expression vectors useful in the context of the disclosure include pBIO1, pBI101.2, pBI101.3, pBI121 and pBIN19 (Clontech). Examples of useful animal expression vectors in the context of the disclosure include pcDNA, pEUK-CI, pMAM and pMAMneo (Clontech). In some embodiments, a bicistronic IRES vector (eg, from Clontech) is used to include both a nucleic acid encoding an antigen-binding receptor and an inducible expression construct described herein. In some embodiments, a recombinant expression vector is a viral vector. Suitable viral vectors include, without limitation, retroviral, alphaviral, vaccinal, adenoviral, adeno-associated viral, herpes viral, and fowlpox viral vectors, and preferably have a native or genetically engineered ability to transform an immune cell (eg. g., T cell). Recombinant expression vectors can be prepared using standard recombinant DNA techniques described, for example, in Sambrook et al., Molecular Cloning: A Laboratory Manual, 3 a ed., Cold Spring Harbor Press, Cold Spring Harbor, N.Y. 2001; and Ausubel et al., Current Protocols in Molecular Biology, Greene Publishing Associates and John Wiley & Sons, NY, 1994. Expression vector constructs, which are circular or linear, can be prepared to contain a functional replication system in a cell. prokaryotic or eukaryotic host. Replication systems can be derived, e.g. eg, from ColEI, plasmid 2p, A, SV40, bovine papillomavirus, and the like. A recombinant expression vector may include one or more marker genes, which allow selection of transformed or transfected hosts. Marker genes include biocide resistance, e.g. eg, resistance to antibiotics, heavy metals, etc. complementation in an auxotrophic host to provide prototrophin, and the like. Suitable marker genes for recombinant expression vectors include, for example, neomycin / G418 resistance genes, puromycin resistance genes, hygromycin resistance genes, histidinol resistance genes, tetracycline resistance genes, ampicillin. Useful vectors in the context of the disclosure may be "naked" nucleic acid vectors (ie, vectors that have little or no encapsulating protein, sugars, and / or lipids), or vectors complexed with other molecules. Other molecules that can be suitably combined with the vectors include, without limitation, viral coats, cationic lipids, liposomes, polyamines, gold particles, and targeting moieties such as ligands, receptors, or antibodies that target cellular molecules. Vector DNA can be introduced into a cell, e.g. eg, an immune cell, by conventional transformation or transfection techniques. As used herein, the terms "transformation" and "transfection" are intended to refer to a variety of art-recognized techniques for introducing foreign nucleic acid (eg, DNA) into a cell, including calcium phosphate or calcium chloride co-precipitation, DEAE-dextran mediated transfection, lipofection, gene gun or electroporation. Protein Therapeutic Agents In some aspects, gene-encoded polypeptides that can be included in an expression construct described herein can be produced and used as therapeutic agents instead of, or in addition to being produced by, a cellular therapeutic agent described herein. Such polypeptides may be included in a composition, e.g. g., a pharmaceutical composition, and used as a protein therapeutic agent. For example, a protein therapeutic agent that includes a polypeptide that is or comprises a target for a cellular therapeutic agent, e.g. eg, a CAR-T cell or ADC, may be administered in combination with said cellular therapeutic agent, e.g. eg, a CAR-T cell or ADC. In one example, a therapeutic protein includes an antibody fusion protein that contains an antigen-binding fragment of an antibody (eg, one or more of the types described herein) that binds an antigen (eg, eg, one or more of the types described herein). In another example, an antibody fusion protein includes a bispecific antibody (or fragment) that binds two antigens. In some embodiments, such a bispecific antibody binds to one or more TAA and / or TSA targets, e.g. i.e., that together define a specific tumor type. Examples of such combinations of TAA and / or TSA targets that allow specific recognition of a tumor type include, e.g. eg, CD70 and carbonic anhydrase IX (renal cell carcinoma), MUC16 and mesothelin (ovarian cancer), and many others. Antigen-binding fragments of this type (eg, bispecific) are in turn fused to a polypeptide antigen recognized by a cellular therapeutic agent, e.g. eg, a CAR-T cell. An illustrative polypeptide antigen is an Ig domain of CD19 that is recognized by CAR-CD19 T cells. The modular characteristics of antibody antigen recognition domains allow consideration of many combinations of antigen recognition domains fused to target polypeptides for a cellular therapeutic agent. In some embodiments, a polypeptide antigen, e.g. eg, one recognized by a cellular therapeutic agent, is fused to the amino (N) terminus of an antigen-binding fragment. In some embodiments, a polypeptide antigen is fused to the carboxy (C) terminus of an antigen-binding fragment. In particular embodiments, a proteinaceous therapeutic agent is or includes an Fe-based construct described herein. A variety of methods for making polypeptides are known in the art and can be used to make a polypeptide for inclusion in a protein therapeutic agent. For example, a polypeptide can be produced recombinantly using a host cell system designed to express a nucleic acid encoding the polypeptide. Recombinant expression of a gene may include construction of an expression vector containing a polynucleotide encoding the polypeptide. Once a polynucleotide has been obtained, a vector for the production of the polypeptide can be produced by recombinant DNA technology using techniques known in the art. Known methods can be used to construct expression vectors containing appropriate polypeptide coding sequences and transcriptional and translational control signals. These methods include, for example, in vitro recombinant DNA techniques, synthetic techniques, and in vivo genetic recombination. An expression vector can be transferred into a host cell by conventional techniques, and the transfected cells can then be cultured by conventional techniques to produce the polypeptide. A variety of host expression vector systems can be used (see, eg, US Patent No. 5,807,715). Host expression systems of this type can be used to produce polypeptides and, where desired, subsequently purified. Host expression systems of this type include microorganisms such as bacteria (eg, E. coli and B. subtilis) transformed with recombinant bacteriophage DNA, plasmid DNA, or cosmid DNA expression vectors containing nucleotide coding sequences. polypeptides; yeast (eg, Saccharomyces and Pichia) transformed with recombinant yeast expression vectors containing polypeptide-encoding sequences; insect cell systems infected with recombinant virus expression vectors (eg, baculovirus) containing polypeptide-encoding sequences; plant cell systems infected with recombinant virus expression vectors (eg, cauliflower mosaic virus, CaMV; tobacco mosaic virus, TMV) or transformed with recombinant plasmid expression vectors (eg, cauliflower mosaic virus, TMV). , Ti plasmid) containing polypeptide coding sequences; or mammalian cell systems (eg, COS, CHO, BHK, 293, NSO, and 3T3 cells) harboring recombinant expression constructs containing promoters derived from the mammalian cell genome (eg, metallothionein promoter ) or from mammalian viruses (eg, adenovirus late promoter; vaccinia virus 7.5K promoter). For bacterial systems, a number of expression vectors can be used, including, but not limited to the E. coli expression vector pU278 (Ruther et al., 1983, EMBO 12:1791); pIN vectors (Inouye & Inouye, 1985, Nucleic Adds Res. 13:3101-3109; Van Heeke & Schuster, 1989, J. Biol. Chem. 24:5503-5509); and the like. pGEX vectors can also be used to express foreign polypeptides as fusion proteins with glutathione 5-transferase (GST). For expression in mammalian host cells, virus-based expression systems can be used (see, eg, Logan 8i Shenk, 1984, Proc Natl Acad Sci USA 8 1:355-359). The efficiency of expression can be enhanced by the inclusion of appropriate transcriptional enhancer elements, transcriptional terminators, etc. (see, eg, Bitner et al. 1987, Methods In Enzymol. 153:516-544). In addition, a host cell strain can be chosen that modulates the expression of inserted sequences, or modifies and processes the gene product in the specific manner desired. Different host cells have characteristic and specific mechanisms for post-translational processing and modification of proteins and gene products. Appropriate cell lines or host systems can be chosen to ensure correct modification and processing of the expressed polypeptide. Such cells include, for example, established mammalian cell lines and insect cell lines, animal cells, fungal cells, and yeast cells. Mammalian host cells include, e.g. eg, the BALB / c mouse myeloma line (NSO / 1, ECACC No: 85110503); human retinoblasts (PER.C6, CruCell, Leiden, The Netherlands); monkey kidney CV1 line transformed by SV40 (COS-7, ATCC CRL 1651); human embryonic kidney line (293 or 293 cells subcloned for growth in suspension culture, Graham et al., J. Gen Virol., 36:59, 1977); human fibrosarcoma cell line (eg, HT1080); baby hamster kidney cells (BHK, ATCC CCL 10); Chinese hamster ovary cells + / -DHFR (CHO, Urlaub and Chasin, Proc. Natl. Acad. Sci. USA, 77:4216, 1980); mouse sertoli cells (TM4, Mather, Biol. Reprod., 23:243-251, 1980); monkey kidney cells (CV1 ATCC CCL 70); African green monkey kidney cells (VERO-76, ATCC CRL-1 587); human cervical carcinoma cells (HeLa, ATCC CCL 2); canine kidney cells (MDCK, ATCC CCL 34); buffalo rat liver cells (BRL 3A, ATCC CRL 1442); human lung cells (W138, ATCC CCL 75); human liver cells (Hep G2, HB 8065); mouse mammary tumor (MMT 060562, ATCC CCL51); TRI cells (Mather et al., Annals N.Y. Acad. Sel., 383:44-68, 1982); MRC 5 cells; FS4 cells; and a human hepatoma line (Hep G2). For long-term, high-yield production of recombinant proteins, host cells are genetically engineered to stably express a polypeptide. Host cells can be transformed with DNA controlled by appropriate expression control elements known in the art, including promoters, enhancers, sequences, transcription terminators, polyadenylation sites, and selectable markers. Methods commonly known in the art of recombinant DNA technology can be used to select a desired recombinant clone. Once a protein described herein has been produced by recombinant expression, it can be purified by any method known in the art for purification, for example, by chromatography (eg, ion exchange, affinity, and liquid chromatography). column by sizes), centrifugation, differential solubility, or by any other standard technique for protein purification. For example, an antibody can be isolated and purified by appropriately selecting and combining affinity columns such as a Protein A column with columns for chromatography, filtration, ultrafiltration, desalting procedures, and dialysis (see Antibodies: A Laboratory Manual, Ed Harlow, David Lane, Cold Spring Harbor Laboratory, 1988). Also, as described herein, a polypeptide can be fused to heterologous polypeptide sequences to facilitate purification. Alternatively or additionally, a polypeptide may be partially or fully prepared by chemical synthesis. Alternatively or additionally, a polypeptide can be purified from natural sources. Management Certain embodiments of the disclosure include methods of administering to a subject a cellular therapeutic agent described herein (or a population thereof), a proteinaceous therapeutic agent described herein, a composition comprising a cellular therapeutic agent, and / or a composition comprising a proteinaceous therapeutic agent, e.g. eg, in an amount effective to treat a subject. In some embodiments, the method effectively treats cancer in the subject. In some embodiments, an immune cell is obtained from a subject and transformed, e.g. eg, is transduced, with an inducible expression construct or a constitutive expression construct described herein, e.g. eg, an expression vector comprising an inducible expression construct or a constitutive expression construct described herein, to obtain a cellular therapeutic agent. Thus, in some embodiments, a cellular therapeutic agent comprises an autologous cell that is administered to the same subject from which an immune cell was obtained. Alternatively, an immune cell is obtained from a subject and transformed, e.g. eg, is transduced, with an inducible expression construct or a constitutive expression construct described herein, e.g. eg, an expression vector comprising an inducible expression construct or a constitutive expression construct described herein, to obtain a cellular therapeutic agent that is allogeneically transferred to another subject. In some embodiments, a cellular therapeutic agent is autologous to a subject, and the subject may be immunologically untreated, immunized, diseased, or in another state prior to isolation of an immune cell from the subject. In some embodiments, additional steps may be performed prior to administration to a subject. For example, a cellular therapeutic agent can be expanded in vitro after contacting (eg, transducing or transfecting) an immune cell with an inducible expression construct or a constitutive expression construct described herein (eg, transducing or transfecting). , an expression vector comprising an inducible expression construct or a constitutive expression construct), but before administration to a subject. In vitro expansion may continue for 1 day or more, e.g. eg, 2 days or more, 3 days or more, 4 days or more, 6 days or more, or 8 days or more, before administration to a subject. Alternatively, or in addition, in vitro expansion may proceed for 21 days or less, e.g. eg, 18 days or less, 16 days or less, 14 days or less, 10 days or less, 7 days or less, or 5 days or less, before administration to a subject. For example, in vitro expansion may proceed for 1-7 days, 2-10 days, 3-5 days, or 8-14 days prior to administration to a subject. In some embodiments, during in vitro expansion, a cellular therapeutic agent may be stimulated with an antigen (eg, a TCR antigen). Antigen-specific expansion may optionally be supplemented by expansion under conditions that non-specifically stimulate lymphocyte proliferation such as, for example, anti-CD3 antibody, anti-Tac antibody, anti-CD28 antibody, or phytohemagglutinin (PHA). The expanded cellular therapeutic agent may be administered directly to a subject or may be frozen for future use, ie, subsequent administrations to a subject. In some embodiments, a cellular therapeutic agent is treated ex vivo with interleukin-2 (IL-2) prior to infusion into a cancer patient, and the cancer patient is treated with IL-2 after infusion. Furthermore, in some embodiments, a cancer patient may undergo preparative lymphodepletion-the temporary ablation of the immune system-prior to the administration of a cellular therapeutic agent. A combination of IL-2 treatment and preparative lymphodepletion can enhance the persistence of a cellular therapeutic agent. In some embodiments, a cellular therapeutic agent is transduced or transfected with a nucleic acid encoding a cytokine, which nucleic acid can be engineered to provide constitutive, regulatable, or temporally controlled expression of the cytokine. Suitable cytokines include, for example, cytokines that act to increase T cell survival during the contraction phase, which may facilitate the formation and survival of memory T cells. In certain embodiments, a cellular therapeutic agent is administered prior to, substantially simultaneously with, or after the administration of another therapeutic agent, such as a cancer therapeutic. The anticancer therapeutic agent may be, e.g. eg, a chemotherapeutic agent, a biological agent, or radiation treatment. In In some embodiments, a subject receiving a cellular therapeutic agent is not administered treatment that is sufficient to cause immune cell depletion, such as lymphodepleting chemotherapy or radiation therapy. A cell therapeutic agent described herein may be formed as a composition, e.g. eg, a cellular therapeutic agent and a pharmaceutically acceptable carrier. In certain embodiments, a composition is a pharmaceutical composition comprising at least one cellular therapeutic agent described herein and a pharmaceutically acceptable carrier, diluent, and / or excipient. Pharmaceutically acceptable carriers described herein, for example, carriers, adjuvants, excipients, and diluents, are well known and readily available to those skilled in the art. Preferably, the pharmaceutically acceptable carrier is chemically inert to the active agent(s), e.g. eg, a cellular therapeutic agent, and does not cause harmful side effects or toxicity under the conditions of use. A composition may be formulated for administration by any suitable route such as, for example, intravenous, intratumoral, intraarterial, intramuscular, intraperitoneal, intrathecal, epidural, and / or subcutaneous routes of administration. Preferably, the composition is formulated for a parenteral route of administration. A composition suitable for parenteral administration may be an isotonic aqueous or nonaqueous sterile injection solution, which may contain antioxidants, buffers, bacteriostatic agents and solutes, for example, which render the composition isotonic with the blood of the intended recipient. A sterile aqueous or non-aqueous suspension may contain one or more suspending agents, solubilizers, thickening agents, stabilizers and preservatives. The dosage administered to a subject, particularly a human, will vary with the particular embodiment, the composition employed, the method of administration, and the particular site and subject being treated. However, one dose must be sufficient to provide a therapeutic response. A physician skilled in the art can determine the therapeutically effective amount of a composition to be administered to a human or other subject for the purpose of treating or preventing a particular medical condition. The precise amount of the composition required to be therapeutically effective will depend on numerous factors, e.g. eg, such as the specific activity of the cellular therapeutic agent, and the route of administration, as well as many subject-specific considerations, which are within those of skill in the art. Any suitable number of cellular therapeutic cells can be administered to a subject. While a single cell therapeutic cell described herein is capable of expanding and providing therapeutic benefit, in some embodiments 10 2 or more, e.g. eg 10 3 or more, 10 4 or more, 10 5 or more, or 10 8 or more cellular therapeutic cells. Alternatively or additionally, 10 12 or less, e.g. eg 10 11 or less, 10 9 or less, 10 7 or less, or 10 5 or less cellular therapeutic cells described herein are administered to a subject. In some embodiments, 10 2 -10 5 , 10 4 -10 7 , 10 3 -10 9 or 1O 5 -1O 10 cellular therapeutic cells described herein. A dose of a cellular therapeutic agent described herein may be administered to a mammal at one time or in a series of sub-doses administered over a suitable period of time, e.g. eg, on a daily, semi-weekly, weekly, bi-weekly, semi-monthly, bi-monthly, semi-annual or yearly basis, as required. A dosage unit comprising an effective amount of a cellular therapeutic agent in a single daily dose, or the total daily dosage may be administered in two, three, four or more divided doses administered daily, as needed. A polypeptide described herein can be incorporated into a pharmaceutical composition (eg, for use as a protein therapeutic agent). Pharmaceutical compositions comprising a polypeptide can be formulated by methods known to those of skill in the art (see, eg, Remington's Pharmaceutical Sciences pp. 1447-1676 (Alfonso R. Gennaro, ed, 19 a ed 1995)). The pharmaceutical composition may be administered parenterally in the form of an injectable formulation comprising a sterile solution or suspension in water or other pharmaceutically acceptable liquid. For example, a pharmaceutical composition can be formulated by suitably combining a polypeptide with pharmaceutically acceptable carriers or media such as sterile water and physiological saline, vegetable oil, emulsifier, suspending agent, surfactant, stabilizer, flavoring excipient, diluent, carrier, preservative, etc. binder, followed by mixing in a unit dosage form required for generally accepted pharmaceutical practices. The amount of active ingredient included in the pharmaceutical preparations is such that a suitable dose within the designated range is provided. The sterile composition for injection can be formulated in accordance with conventional pharmaceutical practices using distilled water for injection as a vehicle. For example, physiological saline or an isotonic solution containing glucose and other supplements such as D-sorbitol, D-mannose, D-mannitol and sodium chloride can be used as an aqueous solution for injection, optionally in combination with an agent. suitable solubilizer, for example alcohol such as ethanol, and polyalcohol such as propylene glycol or polyethylene glycol, and a nonionic surfactant such as polysorbate 80™, HCO-50 and the like. Non-limiting examples of the oily liquid include sesame oil and soybean oil, and it may be combined with benzyl benzoate or benzyl alcohol as a solubilizing agent. Other items that may be included are a buffer such as a phosphate buffer, or sodium acetate buffer, a calming agent such as procaine hydrochloride, a stabilizer such as benzyl alcohol or phenol, and an antioxidant. The formulated injection can be packaged in an ampoule adequate. The route of administration may be parenteral, for example, administration by injection, transnasal administration, transpulmonary administration, or transcutaneous administration. Administration can be systemic or local by intravenous injection, intramuscular injection, intraperitoneal injection, subcutaneous injection. A suitable means of administration can be selected based on the age and condition of the subject. A single dose of a pharmaceutical composition containing a polypeptide can be selected from a range of 0.001 to 1000 mg / kg of body weight. On the other hand, a dose in the range of 0.001 to 100,000 mg / body weight can be selected, but the present disclosure is not limited to such ranges. The dose and the method of administration may vary depending on the weight, age, condition and the like of the subject, and may be appropriately selected as necessary by those skilled in the art. tumors The present disclosure provides technologies useful in the treatment of any tumor. In some embodiments, a tumor is or comprises a hematologic malignancy, including but not limited to acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, AIDS-related lymphoma, Hodgkin's lymphoma, non-Hodgkin's lymphoma, Langerhans cell histiocytosis, multiple myeloma, or myeloproliferative neoplasms. In some embodiments, a tumor is or comprises a solid tumor, including but not limited to breast carcinoma, squamous cell carcinoma, colon cancer, head and neck cancer, ovarian cancer, lung cancer, mesothelioma , genitourinary cancer, rectal cancer, gastric cancer, or esophageal cancer. In some particular embodiments, a tumor is or comprises an advanced tumor and / or a refractory tumor. In some embodiments, a tumor is characterized as advanced when certain pathologies are observed in a tumor (eg, in a tissue sample, such as a biopsy sample, obtained from a tumor) and / or when cancer patients with such tumors are typically considered non-candidates for conventional chemotherapy. In some embodiments, pathologies that characterize tumors as they progress may include tumor size, altered expression of genetic markers, invasion of adjacent organs and / or lymph nodes by tumor cells. In some embodiments, a tumor is characterized as refractory when patients having said tumor are resistant to one or more known therapeutic modalities (eg, one or more conventional chemotherapy regimens) and / or when a particular patient has demonstrated resistance. (eg, no response) to one or more of said known therapeutic modalities. Melanoma Melanoma is the fifth most common type of newly diagnosed cancer in American men and the seventh most common type in American women. Incidence and mortality rates for invasive melanoma are highest in whites, who have a much higher risk of developing melanoma than African Americans. Among people younger than 45 years, incidence rates are higher in women than in men. By age 60, melanoma incidence rates in men are more than double those in women; By the age of 80, men are nearly three times more likely to develop melanoma than women. The annual incidence rate of melanoma among whites increased by more than 60 percent from 1991 to 2011. The incidence of melanoma has increased more rapidly among whites age 65 and older than any other group. Risk factors for melanoma include having fair skin that burns easily, high lifetime exposure to natural or artificial sunlight, a history of sunburn blistering (particularly at a young age), many common tumors , a personal or family history of nevi or dysplastic melanoma, and being white. Standard treatments for melanoma include surgery, chemotherapy, radiation therapy, targeted therapy, and biological therapy. Lung cancer Lung cancer is the second most common cancer and the leading cause of cancer-related death in both men and women in the United States. The total mortality rate for lung and bronchial cancers rose steadily throughout the 1980s, peaked in the 1990s, and has been slowly declining since 2001. Trends in lung cancer incidence and rates of mortality have closely mirrored historical patterns of smoking prevalence, after accounting for a lag period. Because smoking prevalence peaked later in women than in men, lung cancer incidence and death rates began to decline later in women than in men. The incidence rate has been declining since the mid-1980s in men, but only since the mid-2000s in women; the mortality rate began to decline in 1991 in men and not until 2003 in women. Incidence and mortality rates are highest among African-American men, followed by white men. Although smoking is the leading cause of lung cancer, the risk of breast cancer lung is also increased by exposure to secondhand smoke; environmental exposures, such as radon, workplace toxins (eg, asbestos, arsenic), and air pollution. Standard treatments for lung cancer include surgery, radiation therapy, chemotherapy, targeted therapy, laser therapy, photodynamic therapy, cryosurgery, endoscopic stenting, and electrocautery. Head and neck cancer Head and neck cancers, which include cancers of the oral cavity, larynx, pharynx, salivary glands, and nose / nasal passages, account for approximately three percent of all malignancies in the United States. Alcohol and tobacco are the two most important risk factors for head and neck cancers, with at least 75 percent of head and neck cancers caused by alcohol and tobacco use. Other risk factors may include infection with the human papillomavirus, especially HPV-16; consumption of pann (betel chewing), mate, and certain canned or salted foods; poor oral health, occupational or radiation exposure; Epstein-Barr virus infection; and ancestry. Colorectal cancer Colorectal cancer is the third most common non-skin cancer in both men and women. It is the second leading cause of cancer-related mortality in the United States. Over the past decade, colorectal cancer incidence and death rates have decreased in all racial / ethnic populations except American Indians / Alaska Natives. Men and women have similar incidence rates up to age 39 years; at age 40 and older, rates are higher in men. There are differences between racial / ethnic groups in both incidence and mortality. African Americans have higher death rates than all other racial / ethnic groups and higher incidence rates than all American Indians / Alaska Natives. Incidence and mortality rates are lowest among Hispanics and Asian / Pacific Islanders. The global incidence of colorectal cancer and mortality rates have decreased over the last two decades; these declines have been largely attributed to the increased use of screening assays. Risk factors for colorectal cancer, including increasing age, colorectal polyps, a family history of colorectal cancer, certain genetic mutations, excessive alcohol use, obesity, being physically inactive, cigarette smoking, and a history of inflammatory bowel disease. Standard treatments for colorectal cancer include surgery, chemotherapy, radiation therapy, cryosurgery, radiofrequency ablation, and targeted therapy. lymphoma Lymphoma, including Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL), is the most common blood cancer in the United States and is estimated to account for approximately 5 percent of all new cancers diagnosed in the United States in 2014. Nearly 71,000 new cases of NHL and nearly 9,200 new cases of Hodgkin lymphoma are estimated in 2014. Incidence rates for Hodgkin lymphoma are higher for whites and African Americans; death rates are higher for whites, Hispanics, and African Americans. Risk factors for Hodgkin lymphoma and NHL include being male, having a weakened immune system, or being infected with the human immunodeficiency virus (HIV) or Epstein-Barr virus. Infection with Helicobacter pylori or human T-cell leukemia / lymphoma virus type 1 (HTLV-1) increases the risk of certain types of NHL. The risk of NHL increases with age, while the risk of Hodgkin's lymphoma is higher in both early adulthood and later life. Standard treatments for both types of lymphoma are chemotherapy, radiation therapy, and stem cell transplantation. Additional standard therapies include surgery for Hodgkin's lymphoma and targeted therapy, plasmapheresis, watchful waiting, and biologic therapy for NHL. B cell tumors In some embodiments, a B cell-specific antibody (or portion thereof) / CD19 fusion protein or CD19-specific antibody (or portion thereof) / B cell fusion protein described herein is used to treat a subject. having a B cell tumor. In some embodiments, an scFv / CD19 fusion protein, e.g. eg, an anti-CD20 scFv / CD19 fusion protein or an anti-CD20 scFv / CD19 fragment fusion protein to treat a subject having a B cell tumor. In some embodiments, a CD19 / CD19 fusion protein is used. scFv, e.g. eg, an anti-CD20 CD19 / scFv fusion protein or an anti-CD20 CD19 / scFv fragment fusion protein for treating a subject having a B-cell tumor. In some embodiments, a B cell-specific antibody (or part thereof) / B cell antigen fusion protein or a B cell antigen (or part) / B cell-specific antibody (or part) fusion protein is used to treat a subject having a B cell tumor. In some embodiments, a fusion protein that includes (i) CD22 or part (eg, one or more of domains 1-3), CD79 or part (eg, CD79a or CD79b), and (ii) an antibody specific for B cells or part (eg, an anti-CD19, CD20, CD21, CD22, CD72, or CD180 scFv) is used to treat a subject with a B-cell tumor. In some embodiments, a fusion protein including a B cell-specific antibody (or part thereof) and CD20 (or part) is used to treat a subject having a B cell tumor. In some embodiments, a fusion protein is used that includes a B cell-specific antibody (or part thereof) and a portion of CD20 that is or includes an epitope of CD20 (as described, e.g. ., in Natarajan et al., Clin. Cancer Res. 19:6820-9 (2013)) to treat a subject having a B-cell tumor. In some embodiments, a subject having a B cell tumor is treated with one or more of these fusion proteins as a proteinaceous therapeutic. In some embodiments, a subject having a B cell tumor is treated with a cellular therapeutic agent that includes a constitutive expression construct described herein that encodes one or more of these fusion proteins. In some embodiments, a subject having a B cell tumor is treated with a naked nucleic acid encoding one or more of these fusion proteins, or is treated with a viral vector described herein that includes a nucleic acid encoding said fusion protein. fusion protein. Hematotologic Malignant Tumors In some embodiments, a fusion protein described herein that includes (i) an antigen-binding protein that binds a TSA and (ii) CD19 or a portion thereof is used to treat a subject having a hematologic malignancy. In some embodiments, a TSA-binding protein (eg, an anti-TSA antibody (or part thereof) / CD19 fusion protein or a CD19 / TSA-binding protein fusion protein (eg. , anti-TSA antibody) is used to treat a subject having a hematologic malignancy In some embodiments, a hematologic malignancy is a hematologic malignancy of cells not defined by CD19 expression In some embodiments, a hematologic malignancy may be a non-B cell lineage malignancy. In some embodiments, a hematologic malignancy may include, for example, a myeloid malignancy (eg, acute myeloid malignancy), plasma cell malignancy, and malignant tumor. myelodysplastic.In some embodiments, a TSA-binding protein (eg, an anti-TSA antibody) can bind to any known TSA, eg, any TSA described herein.In some embodiments, a TSA is ROR1, BCMA, CS1, CD33, CD123 , CD38, CD138 or CLL-1 / CLECK12A. In some embodiments, a fusion protein described herein that includes (i) an antigen-binding protein that binds to a TSA and (ii) a B cell antigen or a portion thereof is used to treat a subject who has a hematologic malignancy. In some embodiments, a TSA binding protein (eg, an anti-TSA antibody (or part thereof) / B cell antigen fusion protein or a B cell antigen / B cell antigen binding protein fusion protein). TSA (eg, anti-TSA antibody) is used to treat a subject having a hematologic malignancy In some embodiments, a fusion protein includes an antigen or B-cell part (eg, CD20 or part (eg, an epitope) as described, eg, in Natarajan et al., Clin. Cancer Res. 19:6820-9 (2013 ), CD22 or part (eg, one or more of domains 1-3), or CD79 or part (eg, CD79a or CD79b)). In some embodiments, a subject having a hematologic tumor is treated with one or more of these fusion proteins as a proteinaceous therapeutic. In some embodiments, a subject having a hematologic malignancy is treated with a cellular therapeutic agent that includes a constitutive expression construct described herein that encodes one or more of these fusion proteins. In some embodiments, a subject having a hematologic malignancy is treated with a naked nucleic acid encoding one or more of these fusion proteins, or is treated with a viral vector described herein that includes a nucleic acid encoding said protein. of fusion. Solid Tumors In some embodiments, a cellular therapeutic agent described herein that includes a constitutive expression construct can be used to treat a subject having a solid tumor. In some embodiments, the constitutive expression construct encodes a fusion protein described herein that includes (i) an antigen-binding protein that targets a TSA, and (ii) a target for a second cellular therapeutic agent, antibody or antibody-drug conjugate. In some embodiments, a cellular therapeutic agent described herein that includes an inducible expression construct can be used to treat a subject having a solid tumor. In some embodiments, the inducible expression construct encodes a fusion protein described herein that includes (i) an antigen-binding protein that targets a TSA or TAA, and (ii) a target for a second therapeutic agent. cell, antibody, or antibody-drug conjugate. In some embodiments, a fusion protein that is or includes a masked construct or part thereof (described herein) is used to treat a subject having a solid tumor. In some embodiments, a fusion protein that includes a masked antigen-binding protein (which, when unmasked, binds TAA described herein) and CD19 or fragment is used to treat a subject having a solid tumor. . In some embodiments, a subject having a solid tumor is treated with one or more of these fusion proteins as a proteinaceous therapeutic. In some embodiments, a subject having a solid tumor is treated with a cellular therapeutic agent that includes a constitutive expression construct described herein that encodes one or more of these fusion proteins. In some embodiments, a subject having a solid tumor is treated with a naked nucleic acid encoding one or more of these fusion proteins, or is treated with a viral vector described herein including a nucleic acid encoding said fusion protein. Combination Therapy As described herein, in some embodiments a cell therapeutic agent and / or a protein therapeutic agent is administered in combination with a second cell therapeutic agent, an antibody-drug conjugate, an antibody and / or a polypeptide. In some embodiments, the degree of targeting and / or killing of a tumor by a second cellular therapeutic agent (eg, a CAR-T cell) is greater than a level observed or measured in the absence of combination therapy. with a cellular therapeutic agent or a protein therapeutic agent described herein. A pharmaceutical composition comprising a cellular therapeutic agent and / or a protein therapeutic agent described herein may optionally contain and / or may be administered in combination with one or more additional therapeutic agents such as a cancer therapeutic, e.g. . eg, a chemotherapeutic agent or a biological agent. Examples of chemotherapeutic agents that can be used in combination with a cellular therapeutic agent described herein include platinum compounds (eg, cisplatin, carboplatin, and oxaliplatin), alkylating agents (eg, cyclophosphamide, ifosfamide, chlorambucil, mustard nitrogen, thiotepa, melphalan, busulfan, procarbazine, streptozocin, temozolomide, dacarbazine, and bendamustine), antitumor antibiotics (eg, daunorubicin, doxorubicin, idarubicin, epirubicin, mitoxantrone, bleomycin, mitomycin C, plicamycin, and dactinomycin), taxanes ( eg, paclitaxel and docetaxel), antimetabolites (eg, 5-fluorouracil, cytarabine, premetrexed, thioguanine, floxuridine, capecitabine, and methotrexate), nucleoside analogs (eg, fludarabine, clofarabine, cladribine, pentostatin and nelarabine), topoisomerase inhibitors (eg, topotecan and irinotecan), hypomethylating agents (eg, azacitidine and decitabine), proteasome inhibitors (eg, bortezomib), ep ipodophyllotoxins (eg. eg, etoposide and teniposide), DNA synthesis inhibitors (eg, hydroxyurea), vinca alkaloids (eg, vicristine, vindesine, vinorelbine, and vinblastine), tyrosine kinase inhibitors (eg, imatinib, dasatinib, nilotinib, sorafenib, and sunitinib), nitrosoureas (eg, carmustine, fotemustine, and lomustine), hexamethylmelamine, mitotane, angiogenesis inhibitors (eg, thalidomide and lenalidomide), steroids (eg, thalidomide, and lenalidomide). , prednisone, dexamethasone, and prednisolone), hormonal agents (eg, tamoxifen, raloxifene, leuprolide, bicaluathmide, granisetron, and flutamide), aromatase inhibitors (eg, letrozole and anastrozole), arsenic trioxide, tretinoin, inhibitors of nonselective cyclooxygenase (eg, nonsteroidal anti-inflammatory agents, salicylates, aspirin, piroxicam, ibuprofen, indomethacin, naprosin, diclofenac, tolmetin, ketoprofen, nabumetone, and oxaprozin), selective cyclooxygenase-2 (COX-2) inhibitors , or any combination of the themselves. Examples of biological agents that can be used in the compositions and methods described herein include monoclonal antibodies (eg, rituximab, cetuximab, panetumumab, tositumomab, trastuzumab, alemtuzumab, gemtuzumab ozogamicin, bevacizumab, catumaxomab, denosumab, obinutuzumab, ofatumumab , ramucirumab, pertuzumab, ipilimumab, nivolumab, nimotuzumab, lambrolizumab, pidilizumab, siltuximab, BMS-936559, RG7446 / MPDL3280A, MEDI4736, tremelimumab, or others listed in Table 1 herein), enzymes (eg, L-asparaginase ), cytokines (eg, interferons and interleukins), growth factors (eg, rj-z colony-stimulating factors and erythropoietin), cancer vaccines, gene therapy vectors, or any combination thereof. In some embodiments, treatment methods described herein are performed on subjects who have failed other treatments of the medical condition or have been less successful in treatment through other means. Additionally, the methods of treatment described herein may be performed in conjunction with one or more additional treatments for the medical condition. For example, the method may comprise administering an anticancer regimen, e.g. eg, non-myeloablative chemotherapy, surgery, hormonal therapy, and / or radiation, before, substantially with, or after administration of a cellular therapeutic agent and / or a protein therapeutic agent described herein, or composition thereof. In certain embodiments, a subject administered a cellular therapeutic agent and / or a proteinaceous therapeutic agent described herein may also be treated with antibiotics and / or one or more additional pharmaceutical agents. Illustrative nucleotide and amino acid sequences of the disclosure are listed in the following Table: Amino Acid SEQ ID NO: Nucleotide SEQ ID NO: Name 1 201 Heavy Chain (HC) of Panitumumab 2 202 Light Chain (LC) of CD19-D1-Panitumumab 3 203 HC of CD19-Dl-Panitumumab 4 204 LC of Panitumumab 5 205 LC -Panitumumab CD19-D1 6,206 Panitumumab HC-CD19-D1 7,207 LY2875358 HC 8,208 CD19-D1-LY2875358 LC 9,209 CD19-D1-LY2875358 HC 10,210 LY2875358 LC 11 211 LC-CD19-D1 from LY2875358 12 212 HC-CD19-D1 from LY2875358 13 213 Construction FMC63 CAR-19 14 214 CD19-D1 15 215 CD19-Dl-huIgGFc 16 216 Trastuzumab scFv (VH / VL) MOC12sc 17 (VH / VL) 18,218 MOC31 scFv (VL / VH) 19,219 LY2875358 scFv (VH / VL) 20,220 LY2875358 scFv (VL / VH) 21,221 Panitumumab scFv (VH / VL) 22,222 Panitumumab scFv) (VL / VH) 23 223 TNF soluble in CD19-D1+2 24 224 Trastuzumab scFv (VH / VL)-CD19-D1 25 225 Trastuzumab scFv (VH / VL)- CD19-D1-huIgGFc 26 226 CD19-Dl-Trastuzumab scFv (VH / VL ) 27 227 CD19-Dl-Trastuzumab scFv (VH / VL)-huIgFc 28 228 CD19-D1+2 29 229 CD19-Dl+D2-huIgGFc 30 230 CD19-D2 31 231 CD19-D2-huIgGFc 32 232 LC of CD19- Dl+2-Panitumumab 33 233 HC of CD19-Dl+2-Panitumumab 34 234 LC-CD19-D1+2 of Panitumumab 35 235 HC-CD19-D1+2 of Panitumumab 36 236 LC of CD19-D1+2-LY2875358 37 237 HC of CD19-D1+2-LY2875358 38 238 LC-CD19-D1+2 of LY2875358 39 239 HC-CD19-D1+2 of LY2875358 40 240 Trastuzumab scFv (VH / VL)-CD19-Dl+2 41 241 Trastuzumab scFv (VH / VL)-CD19-D1 +2-huIgGFc 42 24 2 CD19-Dl+2-Trastuzumab scFv (VH / VL) 43 243 CD19-Dl+2-Trastuzumab scFv (VH / VL)-huIgFc 46 246 human CD69 tGFP-promoter 47 247 human TNFalpha tGFP-promoter 48 248 promoter Mouse CD25-tGFP 49 249 NFAT element x 6 promoter-tGFP 50 250 CD19-ECD-Panitumumab HC 51 251 CD19-ECD-LY2875358 HC 52 252 CD19-ECD-MOC31 scFv (VH / VL) 53 253 CD19-ECD-LY2875358-scFv (VH / VL) 54 254 CD19-ECD -Panitumumab scFv (VH / VL) 55 255 CD19-ECD-Trastuzumab scFv (VH / VL) 56 256 CD19-ECD-huIgGFc-Trastuzumab scFv (VH / VL) 57 257 Her2-ECD-Panitumumab scFv (VH / VL) 58 258 Her2-D4-Panitumumab scFv (VH / VL) 63 263 CD19-ECD-Leul6 scFv (VH / VL) 64 264 CD22-D123-FMC63 scFv (VH / VL) 65 265 CD22-D123-Leul6 scFv (VH / VL) ) 66 266 CMV tGFP-promoter 67 267 CD19-ECD-anti-EGFRvIII scFv (VL / VH) 68 268 CD22-D123-anti-EGFRvIII scFv (VH / VL) 71 271 1-tagged CAR-19 FMC63 construct 72 272 FMC63 CAR-19 construct tagged-2 73 273 CD 19 FMC63 CAR and CMV-n°42 74 274 CD19 FMC63 CAR and CD25-n°42 promoter 75 275 CD19 FMC63 CAR and CD69-n°42 promoter 76 276 CD19 FMC63 CAR and TNFalpha-n°42 promoter 77 277 CD19 FMC63 CAR and NFAT-n°42 promoter 78 278 Leul6 scFv (VH / VL)-huIgFc 79 279 Leul6 scFv (VH / VL) 80 280 Leul6 scFv (VL / VH)-huIgGFc 81 281 Leul6 scFv (VL / VH) 82 282 CD19-Dl+2-Leul6 scFv (VH / VL)-huIgFc 83 283 CD19-Dl+2-Leul6 scFv (VH / VL) 84 284 CD19-Dl+2-Leul6 scFv (VUVH)-huIgGFc 85 285 CD19-Dl+2-Leul6 scFv (VH / VL) 86 286 CD19-D1+2-MOC31 SCFV (VH / VL) 87 287 CD19-Dl+2-Ly2875358 scFv (VH / VL ) 88 288 CD19-Dl+2-Panitumumab scFv (VH / VL) 89 289 C11D5.3 scFv (VL / VH) 90 290 C11D5.3 scFv (VH / VL) 91 291 CD19-D1+2-C11D5.3 scFv (VH / VL) 92 292 CD19-D1+2-C11D5.3 scFv (VH / VL) 93 293 CD19-Dl+2-huIgGFc-Trastuzumab (VH / VL) 94 294 CD19-Dl+D2-Trastuzumab scFv (VH / VL)-Panitumumab scFv (VH / VL) bispecific 95 295 CD19-Dl+D2-Trastuzumab scFv (VH / VL)-Panitumumab scFv (VL / VH) bispecific 96 296 Trastuzumab scFv-Panitumumab scFv (VH / VL) bispecific 97 297 Trastuzumab scFv -Panitumumab scFv (VL / VH) bispecific 98 298 CMV lentiviral promoter- #42 99 299 CD25 lentiviral promoter- #42 100 300 CD69 lentiviral promoter- #42 101 301 TNFa lentiviral promoter- #42 102 302 promoter of NFATx6 lentiviral- n°42 103 303 Trastuzumab scFv (VH / VL)-huIgFc 104 304 CD19-Dl+2-extended linker-Leul6 scFv (VH / VL)-huIgGFc 105 305 CD19-Dl+2-extended linker-Leul6 scFv (VH / VL) 106 306 CD19-Dl+2-huIgGFc-Leul6 scFv (VH / VL) 107 307 Leul6 SCFV (VH / VL)-CD19-Dl+2-huIgGFc 108 308 EFla - n°72 - T2A - n°42 109 309 EFla - n°42 - T2A - n°72 110 310 N°98 EFla promoter and CMV (variant) 111 311 N°42 EFla promoter (pCDH-EFla) 112 312 CD19 ECD complete In any of the embodiments described herein, a protein and / or construct described herein has an amino acid sequence that is at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a disclosed amino acid sequence, and / or is encoded by a nucleotide sequence that has at least 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity to a nucleotide sequence described herein. All publications, including Gen Bank sequences, cited herein are expressly incorporated herein by reference. EXEMPLIFICATION EXAMPLE 1 Construction and expression of antibody-CD19 fusion proteins Fusion proteins containing CD19 and either full-length antibodies or scFvs were produced using anti-EGFR monoclonal antibody panitumumab, humanized anti-c-MET monoclonal antibody LY2875358 (emibetuzumab), or trastuzumab anti-HER2 monoclonal antibody. The extracellular domain of CD19 that lacks 13 amino acids at the C-terminus and includes the two C2-type Ig domains of CD19 ("CD19-D1 + D2", which includes the non-coding and coding sequences of exons 1-4 in CD19 gene) were fused to full-length antibodies in various orientations as schematically depicted in Figure 13. In some constructs, only CD19 domain 1 ("CD19-D1") or domain 2 ("CD19-D1") was used. CD19-D2") for the fusion protein. In some constructs, the full-length extracellular domain of CD19 ("CD19-ECD"; SEQ ID NO: 112) was used. Panitumumab-CD19 fusion proteins were produced in 293T cells by expression of vectors containing nucleic acids encoding panitumumab-CD19 fusion proteins. The coding sequences for the panitumumab heavy and light chains described herein were used to design synthetic gene sequences in vectors derived from pcDNA-1. The synthetic gene sequences encoded the panitumumab antibody sequences in which the CD19 D1+D2 domain was fused, in frame, to the N-terminus of the heavy chain or the C-terminus of the heavy chain or the N-terminus of the light chain or at the C-terminus of the light chain. The LY2875358-CD19 fusion proteins were produced by expressing vectors containing nucleic acids encoding LY2875358-CD19 fusion proteins in 293T cells. The coding sequences for the heavy and light chains of LY2875358 (described herein) were used to design synthetic gene sequences in vectors derived from pcDNA-1. The synthetic gene sequences encoded the LY2875358 antibody sequences in which the CD19 D1+D2 domain was fused, in frame, to the N-terminus of the heavy chain or the C-terminus of the heavy chain or the N-terminus of the light chain or at the C-terminus of the light chain. In some constructions, only CD19-D1 or CD19-D2 was used for the fusion protein. CD19-ECD was used in some constructs. 293T cells were grown to be 90-95% confluent at the time of transfection. On Day 0, cells were seeded at IxlOeo in 2 ml / well (6 wells per plate) and grown overnight. Cells reached ~90% confluence on day 1. Vector DNAs encoding heavy and light chains were mixed with the transfection reagent. On day 1, 150 µl of Opt¡MEM tm (Gibco) serum-free with 10 pl of Lipofectamine 2000^ (Invitrogen) and incubated at room temperature for 5 minutes (Part A). In another tube, 2.5 pg each of the vector DNAs (heavy and light chains) (Part B) were mixed and then 150 pl serum-free OptiMEM^ was added. Parts A and B were then gently mixed and incubated at room temperature for 20 minutes. The transfection reagent was then added directly to the well with cells in 2 ml of cell culture medium. Cell culture supernatant was collected after 48 hours. Expression levels of panitumumab-CD19 and LY2875358-CD19 fusion proteins were determined by Western blot analysis from cultures of cells expressing the fusion proteins. 1 ml of cell culture supernatant was taken 48 hours after transfection. The cell culture medium was mixed with 20 μl of 50% rProtein A Sepharose Fast Flow slushies in PBS (GE Healthcare) for 3 hours at room temperature, with gentle rocking. Protein A beads, with bound captured antibodies, were centrifuged and washed with PBS. The washing step was repeated. Next, 20 μl of 2x Laemmli sample buffer (Bio-Rad), including DTT as a reducing reagent, was added to remove any antibodies that had been captured by the beads. Usados ​​(10 pl) were loaded onto a 4-20% polyacrylamide gel from Bio-Rad in order to separate proteins under reducing conditions. Heavy and light chains were identified using a peroxidase-coupled anti-human IgG polyclonal antibody. The peroxidase signal was detected enzymatically using Femto West SuperSignal Maximum Sensitivity Substrate (Thermo Fisher), and the resulting bands were imaged using the Chemi Doc MP Imaging System (Bio-Rad) and Image Lab software. Expression levels are depicted in Figures 14A and 14B. Figures 14A and 14B show expression of the following constructs: panitumumab heavy chain (SEQ ID NO:1) and panitumumab light chain (SEQ ID NO:4) ("1+4" construct); Panitumumab CD19-D1+2-LC (SEQ ID NO:32) and Panitumumab HC (SEQ ID NO:1) ("32+1" construct); Panitumumab CD19-D1+2-HC (SEQ ID NO:33) and Panitumumab LC (SEQ ID NO:4) ("33+4" construct); CD19-D1+2 panitumumab LC (SEQ ID NO:34) and panitumumab HC (SEQ ID NO:1) ("34+1" construct); Panitumumab-CD19-Dl+2 HC (SEQ ID NO:35) and Panitumumab LC (SEQ ID NO:4) ("35+4" construct); CD19-D1+2-LC from LY2875358 (SEQ ID NO:36) and HC from LY2875358 (SEQ ID NO:7) ("36+7" construct); CD19-D1+2-HC from LY2875358 (SEQ ID NO:37) and LC from LY2875358 (SEQ ID NO:10) ("37+10" construct); LY2875358-CD19-D1+2 LC (SEQ ID NO:38) and LY2875358 HC (SEQ ID NO:7) ("38+7" construct); LY2875358-CD19-D1+2 HC (SEQ ID NO:39) and LY2875358 LC (SEQ ID NO:10) ("39+10" construct); LY2875358 HC (SEQ ID NO:7) and LY2875358 LC (SEQ ID NO:10) (construction 7+10"). As shown in Figure 14, the CD19-containing heavy and light chains were detectable and passed at a higher molecular weight than the unmodified heavy and light chains (compare, e.g., lanes 1 and 3 in Figure 14A (panituzumab) and lanes 7 and 10 in Figure 14B (LY2875358)). The scFv-CD19 fusion proteins were produced using trastuzumab anti-HER2 antibody scFv and CD19 fused to the N-terminus or C-terminus of the scFv (i.e., the linked VH and VL sequences of the parent antibody), as depicted schematically in Figure 15. The scFv-CD19 fusion proteins were designed to include a C-terminal HIS tag (eg, constructs #40 and 42) or a human IgG ("hulgGFc")-CH2-CH3-hinge ( eg, construction nos. 41 and 43). In some constructions, only CD19-D1 or CD19-D2 was used for the fusion protein. CD19-ECD was used in some constructs. The scFv-CD19 fusion proteins were expressed in 293T cells using the same methods as described above, except that only one vector encoding the sequences to be expressed was used, since the construct is linear. Expression levels of the scFv fusion proteins were determined by Western blot analysis. The Fe-tagged scFv fusion proteins were immunoprecipitated using protein A-coated beads, run on a reducing gel and detected by anti-human IgG peroxidase staining and enzymatic detection. HIS-tagged scFv fusion proteins were immunoprecipitated using anti-HIS resin (R8iD Systems) and detected with a polyclonal anti-HIS antibody-peroxidase conjugate and enzymatic detection. The expression of trastuzumab scFv-CD19 fusion proteins is shown in Figure 16. EXAMPLE 2 Antibody-CD19 fusion proteins are recognized by anti-CD19 antibody The ability of an anti-CD19 antibody (FMC63) to bind to the various antibody-CD19 fusion proteins described in Example 1 was determined using a variety of methods to demonstrate specific binding. Figures 17A-17D depict the binding to FMC63 of the panitumumab-CD19 fusion proteins described in Example 1. ELISA plates (Pierce) were coated with 1 pg / ml anti-human CD19 antibody FMC63 (Millipore) at 4°C. C overnight. The plate was blocked with 0.3% NF milk powder in TBS for 1 hour at room temperature. Cell culture supernatants were added directly to wells in ELISA buffer, followed by serial dilution from 1:3 to 1:2187. ELISA plates were gently washed with TBST (50 mM Tris, 150 NaCl). mM, 0.05% Tween20) in ELISA buffer, three times, and then peroxidase-conjugated polyclonal anti-human IgG was added to detect bound human antibodies. In this assay format, human antibodies are retained by CD19 binding to FMC63 coated on the surface of the plate. Additional controls were performed to demonstrate specificity (represented in Figure 18). "mAb alone" indicates the addition of the parent antibody that does not carry a CD19 fusion, and "mock Tfx" indicates the addition of media from wells that were treated with the transfection protocol, but without added vectors. Binding was shown to be above background for all four fusion proteins tested (corresponding to the N- and C-terminal fusions of CD19 to the heavy and light chains; Figure 18 ). The intensity of binding appeared to reflect the amount of protein expression as demonstrated by Western blots (FIG. 14A). Figures 19A-19D depict the binding of the LY2875358-CD19 fusion proteins described in Example 1 to FMC63 using the same methods as described for the panitumumab-CD19 fusion proteins. As shown in Figure 20, FMC63 binding to LY2875358-CD19 fusion proteins was specific when compared to "mAb alone" and "mock Tfx" controls, as described for the fusion protein example. panitumumab-CD19. This example demonstrates that an anti-CD19 antibody is capable of recognizing antibody-CD19 fusion proteins. Table A summarizes the expression of, and binding of, FMC63 to the antibody-CD19 fusion proteins described in Example 1. TABLE A Shows a summary of the expression of, and FMC63 binding to, various antibody-CD 19 fusion proteins. Figure 21 depicts the binding of the CD19-Dl+2-Trastuzumab scFv (VH / VL) fusion protein (construct #42 described in Example 1) to an ELISA plate coated with FMC63. Bound scFv fusion protein was detected with a peroxidase-coupled anti-HIS antibody. Note that 3B10, an anti-CD19 mAb that binds to the C-terminus of CD19 (lacking construct #42), did not bind. EXAMPLE 3 LY2875358-CD19 fusion proteins bind to A549 carcinoma cells and bind anti-CD19 antibody The ability of a LY2875358-CD19 fusion protein ("37+10" construct described in Example 1) to bind to A549 carcinoma cells and to FMC63 (anti-CD19 antibody) was tested by Fluorescence Activated Cell Sorting (also known as "FACS" or "Flow Cytometry"). A549 cells express the cancer cell-associated protein c-MET that is specifically recognized by LY2875358. LY2875358 HC (SEQ ID NO: 7) and LY2875358 LC (SEQ ID NO: 10) were expressed in 293T cells and cell culture supernatant was incubated with A549 cells. After a 30 min incubation on ice, cells were washed with FACS buffer (PBS with 1% BSA and 0.1% sodium azide). Bound antibody was then detected by incubating the cells with an IgG anti-human IgG-fluorescein isothiocyanate (FITC) conjugate, which emits a fluorescent signal when activated by a specific laser in the flow cytometer. The resulting FACS signal can be seen as an increase in the mean fluorescence intensity (MFI) detected by the instrument, causing the signal to shift further (a right shift as depicted in Figure 22A). A similar shift was detected when the supernatant containing the "37+10" fusion protein construct was incubated with A549 cells. Importantly, the A549 cell-bound "37+10" fusion protein construct could be detected with the anti-CD19 antibody FMC63, as a PE conjugate, in which phycoerythrin (PE) is activated by the Flow Cytometer or as a post-purified antibody bound to a FITC anti-human IgG (Figure 22B to 22C). These results demonstrate that the LY2875358-CD19 fusion protein bound to A549 cells by recognition of c-MET by the antibody binding domains, and was in turn recognized by the anti-CD19 antibody FMC63. Therefore, both the antibody binding domain and CD19 were intact. This example demonstrates that a LY2875358-CD19 fusion protein was able to bind to cells expressing c-MET and to an anti-CD19 antibody. EXAMPLE 4 Trastuzumab scFv-CD19 fusion proteins bind to Her2 and anti-CD19 antibody The capacity of two trastuzumab scFv-CD19 fusion proteins (CD19-Dl+2-Trastuzumab scFv (VH / VL); construction n°42 described in Example 1; and CD19-D1+2-Trastuzumab scFv (VH / VL)-huIgGFc; construct #43 described in Example 1) to bind Her2 and anti-CD19 antibody (FMC63). ELISA plates were coated with 1 pg / ml anti-CD19 FMC63 antibody and cell culture supernatant containing HIS-tagged construct #42 or Fc-fusion construct #43 was added at different dilutions. After incubation for 1 hour at room temperature and washing, purified biotinylated HER2 protein (ACRO Biosystems) at a concentration of 1 pg / ml was added for an additional hour at room temperature, the plate was then washed again and streptavidin-peroxidase was added. to detect HER2-conjugated bound biotin (Figure 23A to 23B). In an additional set of experiments to demonstrate specificity, irrelevant biotinylated proteins were substituted for biotinylated HER2 ("bio-EpCAM", "bio-EGFR"), or the unconjugated form of trastuzumab scFv was used instead of a fusion protein. of trastuzumab scFv-CD19 ("#17-bio-HER2"), or medium alone was added in place of the trastuzumab scFv-CD19 fusion proteins ("medium-bio-HER2"). The results demonstrated the specificity of biotinylated HER2 binding to trastuzumab scFv-CD19 fusion proteins captured on the ELISA plate by anti-CD19 (Figure 24A to 24B). As shown in Figure 24A, construct #42 bound both FMC63 and the Her2 antigen. Figure 24B demonstrates that fusion protein construct #43 also bound FMC63 and the Her2 antigen. This example demonstrates that trastuzumab scFv-CD19 fusion proteins were able to bind the Her2 antigen and an anti-CD19 antibody. EXAMPLE 5 ELISA Analysis of Various Fusion Proteins Methods An ELISA was performed on various fusion proteins described below. Briefly, 96-well plates (Pierce, Cat #15041) were coated with 1.0 pg / ml reagent in 0.1 M carbonate, pH 9.5 overnight at 4C. Plates were then blocked with 0.3% skimmed milk powder (NFD) in TBS (200 µl / well) for 1 h at RT. Plates were then washed 3 times with wash buffer (lx TBST: 0.1 M Tris, 0.5 M NaCl, 0.05% Tween 20). Titrations were performed from undiluted cell culture supernatant or purified protein at 1.0 pg / ml with 3x serial dilutions, 100 µl per well and incubated for 1 h at RT. the tampon dilution is 1% BSA in 1x TBS (0.1 M Tris, 0.5 M NaCl) followed by 3x wash with wash buffer. Secondary reagents (if needed) such as biotinylated reagents were added at a concentration of 1 pg / ml at RT for 1 hour. HRP-conjugated reagents were added at a ratio of 1:2000, applied 100 μl per well, incubated at RT in the dark for 1 h. 100 pl of 1-Step Ultra TMB-ELISA (Thermo Fisher, Prod #34028) was added per well. Plates were read at 405nm when color developed. The following reagents were used: • Human CD19 protein (20-278), Fe Label: ACRO Biosystems, Cat # CD9-H5255 • Human CD19 protein (20-291), His-Tag: ACRO Biosystems, Cat # CD9-H5226 • Anti-CD 19 (3B10): NOVUS, Cat No. NBP2-46116 • Anti-CD 19 (MFC63): Millipore, Cat no. MAB1794 • Human Her2 / ErbB2 Protein, Fe Label: ACRO Biosystems, Cat # HE2-H5253 • Human EGF R Protein, Fe Label: ACRO Biosystems, Cat # EGR-H5252 • Human protein BCMA, Label Fe: R&D Systems. Cat #193-BC-050 • Goat anti-human IgG (H+L) secondary antibody: Thermo Fisher, Cat #31130 • 6x-His Epitope tag antibody: Thermo Fisher, Cat # PA1-983B • 6x-His epitope tag antibody, HRP conjugate: Thermo fisher, Cat no. MA 1-21315-HRP • Pierce-HRP High Sensitivity Streptavidin: Thermo Fisher, Cat #21130 • Goat anti-Mouse IgG (H+L), HRP conjugate: Jackson ImmunoResearch, Cat # 115-035-062 • Goat anti-Human IgG (H+L), HRP conjugate: Jackson ImmunoResearch, Cat # 109-035-088 The following table lists the various fusion proteins tested in this Example: Construction No Description Amino Acid SEO ID NO: Nucleotide SEO ID NO: 28 CD19-D1+2 28 228 29 CD19-Dl+D2-huIgGFc 29 229 33+4 Panitumumab CD19-D1+2-HC and Panitumumab LC 33 / 4 233 / 204 42 CD19-Dl+2-Trastuzumab scFv (VH / VL) 42 242 43 CD19-Dl+2-Trastuzumab scFv (VH / VL)-huIgFc 43 243 52 CD19-ECD-MOC31 scFv (VH / VL) 52 252 53 CD19-ECD-LY2875358-scFv (VH / VL) 53 253 54 CD19- ECD-Panitumumab scFv (VH / VL) 54 254 55 CD19-ECD-Trastuzumab scFv (VH / VL) 55 255 56 CD19-ECD-huIgGFc-Trastuzumab scFv (VH / VL) 56 256 57 Her2-ECD-Panitumumab scFv (VH / VL) 57 257 58 Her2-D4-Panitumumab scFv (VH / VL) 58 258 63 CD19-ECD-Leul6 scFv (VH / VL) 63 263 64 CD22-D123-FMC63 scFv (VH / VL) 64 264 65 CD22- D123-Leul6 scFv (VH / VL) 65 265 67 CD19-ECD-anti-EGFRvIII scFv (VL / VH) 67 267 68 CD22-D123-anti-EGFRvIII scFv (VH / VL) 68 268 82 CD19-Dl+2- Leul6 scFv (VH / VL)-huIgFc 82 282 83 CD19-Dl+2-Leul6 scFv (VH / VL) 83 283 89 C11D5.3 scFv (VL / VH) 89 289 90 C11D5.3 scFv (VH / VL) 90 290 91 CD19-D1+2-C11D5.3 scFv (VH / VL) 91 291 92 CD19-D1+2-C11D5.3 scFv (VH / VL) 92 292 93 CD19-Dl+2-huIgGFc-Trastuzumab (VH / VL) 93 293 94 CD19-Dl+D2-Trastuzumab scFv (VH / VL)-Panitumumab scFv (VH / VL) bispecific 94 294 95 CD19-Dl+D2-Trastuzumab scFv (VH / VL)-Panitumumab scFv (VL / VH) bispecific 95 295 96 Trastuzumab scFv- Panitumumab scFv (VH / VL) bispecific 96 296 97 Trastuzumab scFv Panitumumab scFv (VL / VH) bispecific 97 297 Results Figure 25 shows fusion proteins captured on ELISA plates coated with anti-His antibody. As shown in Figure 25, the binding capabilities were demonstrated of C-terminal His-tagged CD19-scFv fusion proteins (FIG. 25, arrows). CD19-ECD-M0C31 scFv (VH / VL) (build n°52) and CD19-ECD-Leul6 scFv (VH / VL) (build n°63) were captured on the ELISA plate through an antibody directed at the C-terminal His tag. Once bound, the fusion proteins were detected using an HRP-coupled anti-CD19 monoclonal antibody 3B10 that recognizes the CD19 protein. Thus, a positive signal demonstrated that both the C-terminus and the N-terminus of the fusion protein were intact and capable of binding. Figure 26 shows fusion proteins captured on ELISA plates coated with anti-His antibody. As shown in Figure 26, the binding capabilities of the C-terminal His-tagged CD19-scFv fusion proteins were demonstrated. A His-tagged CD19 protein (D1+D2; construct #28) was created as a positive control for CD19 recognition. Fusion proteins were captured on the ELISA plate via an antibody directed at the C-terminal His tag. Once bound, the fusion proteins were detected using the anti-CD19 mouse monoclonal antibody FMC63. Bound FMC63 was detected using an HRP-coupled polyclonal antibody to the Fe domain of murine IgG. Thus, a positive signal demonstrated that both the C-terminus and the N-terminus of the fusion protein were intact and capable of binding. Figure 27 shows fusion proteins captured on plates coated with anti-FMC63 (anti-CD19), then detected with anti-His-HRP. As shown in Figure 27, the binding capabilities of the C-terminal His-tagged CD19-scFv fusion proteins were demonstrated. The fusion proteins were captured on the ELISA plate coated with the anti-CD19 mouse monoclonal antibody FMC63. FMC63 captures the fusion proteins by binding to the N-terminal CD19 protein. Once bound, the fusion proteins were detected using HRP-coupled anti-His antibody that recognizes the C-terminal His tag on the fusion proteins. Thus, a positive signal demonstrated that both the C-terminus and the N-terminus of the fusion protein were intact and capable of binding. Figures 64A, 64B, and 64C depict the binding of additional CD19-containing fusion proteins (#42, #43, #56, #82, #83, #91, #92, #93 , #94) to an FMC63-coated plate as described for Figure 28. Fusion proteins were detected with peroxidase-coupled anti-His antibody or peroxidase-coupled anti-hlgG antibody. Figure 64D demonstrates estimates of fusion protein construct titers by titration against purified construct #42. Figure 64C demonstrates that the CD19 bispecific fusion protein (construct #94) was expressed, bound by anti-CD19 antibody FMC63, and detected by an anti-His antibody that bound to the C-terminal His tag. This indicates that the protein was intact and that the N and C termini were present. Controls show strong binding by the fusion protein containing the Trastuzumab scFv only (build #42) and by the Trastuzumab scFv-huIgGFc fusion protein (build #43). Moving hulgGFc to a position only C-terminal to the CD19 protein domain resulted in fusion proteins with reduced binding to the FMC63 mAb (build #56 and #93). Figure 28 shows the detection of CD19-anti-Her2 trastuzumab scFv-human Fe fusion proteins (builds #29, 43, 56) in a "sandwich ELISA" format. The human Fc domain was bound to the plate using a polyclonal anti-human IgGFc antibody. Once bound, the fusion proteins were detected using a different anti-human IgGFc polyclonal antibody coupled to HRP. The results demonstrated that these fusion proteins were expressed and that the human Fe domain was present. Figures 29 and 30 show fusion proteins detected by various ELISA formats. Figure 29 shows the capture by anti-CD19 monoclonal antibody FMC63 of multiple fusion proteins (constructs #52, 53, 54, 63) and their detection by HRP-coupled anti-His antibody. Furthermore, Figure 30 shows that the CD19-ECD-Leul6 scFv (VH / VL) fusion protein (construct #63) was detected using the reverse format, in which the protein was captured by the C-terminal His tag and it was then detected by the anti-CD19 mouse monoclonal antibody FMC63 and then anti-mouse IgG-HRP. These results demonstrate that the desired binding properties of these fusion proteins were maintained. Figure 31 shows the results for fusion proteins incorporating CD22 protein domains, or anti-EGFRvIII scFv. Figure 31 demonstrates that two formats in which a CD22 protein, an optimized truncated form encoding the first three N-terminal domains of the extracellular portion of the protein, and specific mutations, can be successfully fused to scFvs. Constructs #64 and #65 were captured via the C-terminal His tag, and CD22 was detected at the N-terminus. In contrast, an identical CD22 protein fused to an anti-EGFRvIII protein was not successfully detected (#68) and neither was a CD19 protein fused to anti-EGFRvIII scFv (#67). Figure 32 shows the results for a protein-antibody fusion protein (construct "33+4") and scFv-protein fusion proteins (constructs #57 and 58) derived from the same antibody, panitumumab. The plate was coated with anti-His antibody, and bound protein was detected with biotinylated EGFR protein and streptavidin-HRP. Figure 32 demonstrates that the panitumumab-derived scFv and panitumumab fusion proteins were competent to bind their antigenic ligand, EGFR, when bound to the plaque via the C-terminal His tag. Figure 32 also shows that Her2 extracellular domains (full-length or domain 4 (D4)-only) do not disrupt panitumumab- and scFv-derived binding function. panitumumab. The Her2 fusion proteins were similar in this respect to the CD19 fusion proteins. Figures 65A to 65D show the capture of various fusion proteins (construct #42, #52, #89, #90, #91, #92, #94, #95, #96). , n°97) by the antigen bound to the plate and its detection by the anti-His antibody coupled to HRP. human BCMA-Fc (Fig. 65A), Her2-Fc (#42, #94) or EGFR-Fc (nO94, #57) (Fig. 65B), and Her-2-Fc or EGFR-Fc, as indicated (FIG. 65D), they were bound to the plate using a polyclonal anti-human IgGFc antibody. Supernatants generated from transfections with the indicated fusion proteins (purified or expressed) were added to the coated plate and allowed to incubate. After washing, bound protein was detected using an HRP-conjugated anti-HIS antibody. This demonstrates that the fusion proteins retain the ability to bind their respective antigens. In addition, fusion protein #94 (Figs. 65B and 65C) and fusion proteins #95, #96, and #97 (Figs. 65C and 65D) were captured via Her2- and EGFR-encoded scFvs , showing that both scFvs were functional in the fusion protein produced. EXAMPLE 6 Analysis of the Target Affinities of Various Fusion Proteins The binding affinities of the fusion protein CD19-Dl+2-Trastuzumab scFv (VH / VL) (construct n°42) for the binding of the CD19 protein to an anti-CD19 monoclonal antibody and for the binding of Trastuzumab scFv to purified Her2 protein. Methods A 96-well ELISA plate was coated with 2 pg / ml anti-CD19 monoclonal antibody FMC63 in PBS. The plate was allowed to incubate overnight at 4°C. The coated plate was washed with PBS and then blocked with PBS / 0.3% skimmed milk powder (NFD) for 30 min at 37°C. Purified CD19-Dl+2-Trastuzumab scFv (VH / VL) fusion protein was diluted in PBS / NFD and added in amounts varying from 0.005 pg / ml to 1 pg / ml, covering more than three logs of final concentration. The fusion protein was allowed to incubate for 1 hour at 37°C, then the plate was washed and the HRP-coupled anti-His antibody was added for 30 minutes at 37°C, then used for enzymatic detection, following instructions. manufacturer. Apparent EC50 was calculated using the 4-parameter curve fitting function of Softmax software. The Her2 binding affinity of the CD19-D1+2-Trastuzumab scFv (VH / VL) fusion protein bound to FMC63 was then assessed. The ELISA plate was coated, washed and incubated with the fusion protein as described above. Then, a Her2-Fc titration was added purified to the wells and allowed to incubate for 1 hour at 37°C. After a wash with PBS, HRP-coupled anti-hlgGFc antibody was added and incubated for 30 minutes at 37°C. HRP was detected by enzymatic reaction following the manufacturer's instructions. The Her2 binding affinity of the CD19-DI+2-Trastuzumab scFv (VH / VL) fusion protein was also compared to the Her2 binding affinity of the parent scFv (trastuzumab) (build #16). The ELISA plate was coated with 2 pg / ml HER2-hFc in PBS overnight at 4°C. The plate was washed with PBS, then blocked with PBS / NFD for 1 hour at 37°C. After another wash with PBS, the proteins or supernatants were added in a titration to the plate and allowed to bind for 1 hour at 37°C. The plate was washed again with PBS and HRP-coupled anti-His antibody was added for 30 minutes at 37°C, and then developed using the manufacturer's instructions. Apparent EC50's were calculated as described above. Results Purified CD19-Dl+2-Trastuzumab scFv (VH / VL) fusion protein bound to FMC63 antibody with an apparent EC50 of 0.14 nM (Figure 33), which was very similar to the EC50 of 0.4 nM reported for CD19 binding purified to the FMD63-derived CAR scFv construct (Nicholson, I.C. Et al. 1998. Mol. Immunol., 34:1157-1165). The binding affinity of the fusion protein FMC63-CD19-Dl+2-Trastuzumab scFv (VH / VL) to Her2 was evaluated in ELISA format. As shown in Figure 34, the apparent affinity in this format was 0.18 nM (circles show purified CD19 protein control, which did not bind to Her2 and thus was not detected). The affinity of the scFv in the fusion protein was compared to the expressed anti-Her2 scFv. The apparent affinities of the protein supernatants were very similar for Her2, with the expressed fusion protein binding having an apparent affinity of 0.33 nM compared to the apparent affinity of the expressed scFv of 0.77 nM (Figure 35). The affinity of the purified fusion protein was 0.4 nM, showing that the purification had no impact on the binding capacity of the Her2 fusion protein (FIG. 35). These affinities are very similar to those reported for the trastuzumab scFv (0.3 nM, Zhao et al. 2009 J. Immunol. 183:5563-5574). EXAMPLE 7 Analysis of Various Fusion Proteins by Flow Cytometry Methods If necessary, cells to be analyzed were detached with 0.5 mM EDTA in PBS followed by washing 2x with ice-cold FACS buffer (1% BSA + 0.1% Sodium Azide in PBS). The Cells were resuspended in FACS buffer (5xl0 5 / 100pl / test). Purified protein (up to 10 pg / ml as final concentration) or 200 µl of supernatant was added to cells suspended in 100 µl of FACS buffer followed by incubation at 4°C for 30 minutes. After washing 2x with ice-cold FACS buffer, cells were resuspended in FACS buffer (5x105 / 100 pl / test) and incubated with detection antibody in FACS buffer at 4°C for 30 minutes. If a secondary antibody was needed, the cells were washed and the secondary antibody was added at the desired concentration for 30 minutes at 4°C for the detection step. Samples were then washed 2 times with ice-cold FACS buffer, cells were fixed with 2% paraformaldehyde in PBS and analyzed on the Accuri Flow Cytometer (BD Biosciences). Several constructs described in Example 5 were tested. Additional constructs are listed in the following table: Construction N° Description Amino acid SEO ID NO: Nucleotide SEO ID NO: 84 CD19-Dl+2-Leul6 scFv (VL / VH)-huIgGFc 84 284 85 CD19-Dl+2-Leul6 scFv (VH / VL) 85 285 Results The stable transferring line 293-CD20 was incubated with 200 μl of CD19-ECD-Leul6 scFv (VH / VL) fusion protein (build #63) and then FMC63-PE conjugated anti-CD19 monoclonal antibody (also known as " 293-CD20 + n°63 + FMC63-PE"). As shown in Figure 35, a small positive shift was observed in the Flow Cytometry (FACS) profile relative to controls. Figure 37 shows the analysis of 293-CD20 + 200 pl CD19-Dl+2-Leul6 scFv (VH / VL) fusion protein (build #83). FMC63-PE was used to detect the fusion protein bound to 293-CD20 cells. The results showed a better shift in the FACS profile than did #63. This is because the truncated CD19 protein (DI + D2, i.e. exons 1 to 4 scrambled and lacking the last 13 amino acids of the extracellular domain) binds more efficiently to FMC63 in this fusion protein format (comparing #63 and #83) which makes it the full-length extracellular domain. Additionally, Figure 66A shows analysis of varying concentrations of construct #83 bound to 293-CD20 cells detected by α-HIS-PE. Figure 66B shows analysis of varying concentrations of construct #83 bound to 293-CD20 cells detected by FMC63-PE. These results further support the conclusion that the fusion protein successfully bound CD20 on the cell surface and presented the CD19 domains to be recognized by the detection antibody. Figure 38 shows analysis of 293-CD20 + 200 pl of CD19-Dl+2-Leul6 scFv (VL / VH) fusion protein (build #85). FMC63-PE was used to detect the fusion protein bound to 293-CD20 cells. This result showed a fusion protein in which the Ieul6 scFv was encoded in the reverse direction of #83: thus, #85 encodes VL then VH, while #83 encodes VH then VL. The VL-VH Ieul6 scFv did not bind to the cell and therefore CD19 (the N-terminal component of the fusion protein) was not detected. Figure 39 shows the analysis of 293-CD20 + 200 pl CD19-Dl+2-Leul6 scFv (VH / VL)-huIgGFc fusion protein (build #82). The anti-huIgG-FITC antibody was used to detect the fusion protein bound to 293-CD20 cells. Figure 40 shows the analysis of the anti-huIgG-FITC negative control: 293-CD20 cells + anti-huIgG-FFTC antibody (2 pl). This experiment demonstrated that CD19-Dl+2-Leul6 scFv (VH / VL)-huIgGFc (Figure 39) bound at least 1 log above the negative control (Figure 40) by mean fluorescence intensity (MFI) and that 91.7 % of 293-CD20 cells stained positively on the FACS profile. This demonstrates that the fusion protein that was bound to a human IgG Fe (hinge-CH2-CH3) successfully bound CD20 on the cell surface and presented the C-terminal human IgGFc domain to be recognized by the detection antibody ( anti-human IgG-FITC-conjugate). Additionally, Figure 67A shows analysis of varying concentrations of construct #82 bound to 293-CD20 cells as detected by a-hlgG-FITC. Figure 67B shows analysis of varying concentrations of construct #82 bound to 293-CD20 cells detected by FMC63-PE. These results further support the finding that the fusion protein that bound to a human IgG Fe (hinge-CH2-CH3) successfully bound CD20 on the cell surface and presented the C-terminal IgGFc domain to be recognized by the detection antibody. Figure 41 shows the analysis of 293-CD20 + 200 μl of CD19-Dl+2-Leul6 scFv (VH / VL)-huIgGFc fusion protein (construct #84). The anti-huIgG-FITC antibody was used to detect the fusion protein bound to 293-CD20 cells. This experiment demonstrated that, as with the fusion protein of construct #85, the scFv could not be successfully encoded as VL-VH in this fusion protein format. Figure 42 shows the analysis of 293-CD20 + 200 pl CD22-D123-Leul6 scFv (VH / VL) fusion protein (build #65) + anti-His-PE antibody. Figure 43 demonstrates that the fusion protein CD22-D123-Leul6 scFv (VH / VL), in which the first three domains of CD22 (which were further mutated) were fused with the Leu 16 scFv, was detected on the surface of 293-CD20 cells via an antibody against the C-terminal His tag. Figures 43-45 demonstrate that a fusion protein bridges trastuzumab to Her2-negative / EGFR-positive cells through EGFR binding by the scFv panitumumab. Figure 44 shows the detection control for Her2 cells - A431 + Trastuzumab-PE, showing the background level of binding (A431 cells are Her2-low / negative). Figure 45 shows the analysis of the fusion protein A431 + Her2-ECD-Panitumumab scFv (VH / VL) (build #57) + Trastuzumab conjugated with PE. Figure 45 shows the analysis of fusion protein A431 + Her2-D4-Panitumumab scFv (VH / VL) (build #58) + Trastuzumab conjugated with PE. These results demonstrate that Her2-anti-EGFR scFv fusion proteins bound to an EGFR-positive cell and presented Her2 such that, in turn, it bound to the anti-Her2 monoclonal antibody trastuzumab. Figures 72A through 75B further demonstrate that fusion proteins can bridge antigen-binding domains with other antigen-binding domains. 293T cells were transiently transfected with HER2 or EGFR cDNA expression constructs (Genscript) using lipofectamine 2000 reagent (ThermoFisher), following the manufacturer's instructions. 48 hours after transfection, cells were gently detached from the tissue culture plate using EDTA solution. After washing with FACs buffer, transfected cells were incubated with supernatants containing indicated expressed fusion proteins. All incubations were performed at 4°C. After washing the cells in cold FACs buffer, 2 pg / ml of HER2-huIgGFc or EGFR-huIgGFc was added and incubated with the cells. Bound fusion proteins were detected with anti-huIgGFc-FITC conjugated antibody (Jackson immunoResearch Laboratories, cat no: 100-096-098) in a flow cytometer (Accuri, BD Biosciences). Figures 72A and 72B show control samples that were stained with anti-EGFR or anti-HER2 antibodies to confirm expression. Figures 73A through 73D show the fusion protein expressed by construct #43 binding to cells expressing 293T-Her2. An increase in signal was observed when a fluorescently labeled anti-CD19 antibody (FMC63-PE) (Fig. 73A vs. 73C) or a fluorescently labeled anti-human IgG-Fc (anti-huIgG-Fc-FITC) was present (Fig. 73B). vs. 73D). Figures 74A to 74D show binding of cells expressing constructs #94 and #95 to 293T-Her2. An increase in fluorescent signal for fusion protein #94 was observed when recombinant Fe-tagged EGFR (EGFR-Fc) was incubated with cells bound to fusion protein #94, demonstrating that both anti-HER2 and anti-HER2 scFv -EGFR were functional in the expressed fusion protein. In contrast, construct #95, in which the anti-EGFR scFv is included as VL / VH instead of VH / VL, appeared to bind poorly or not at all to HER2-positive cells. Figures 75A and 75B demonstrate binding of cells expressing fusion protein #94 to 293T-EGFR detected via purified soluble HER2-Fc and detection of huIgG-Fc. EXAMPLE 8 CAR19 T cell targeting and oor art activation of fusion proteins Activation and cytotoxicity of CAR19 T cells was evaluated in the presence of various fusion proteins derived from the expression of specific constructs (described in Example 5) and target cell lines described below. Methods 1, CAR19 T cells targeting BT474 cells by fusion proteins that bind to Her2 BT474 cells were used as target cells expressing Her2. The following samples, expressed by the indicated constructs, were run in duplicate, including: • BT474 + fusion protein construct #42 + CAR-T • BT474 + protein construct #28 + CAR-T • BT474 + CAR-T • BT474 + fusion protein construct #42 or protein construct #28 • BT474 only • CAR-T + fusion protein construct #42 or protein construct #28 • CAR-T only On day 1, the BT474 tumor cell line was seeded at lxlO 4 per well of a flat-bottom 96-well plate (Thermo Fisher, Cat. No. 130188) in cell culture media (RPMI 1640, 10% FBS). A plate for culture and analysis of 24 hours and a second plate for culture and analysis of 48 hours were seeded. On day 2, fusion protein from construct #42 (described in Example 5) or control protein (construct #28 described in Example 5) was added at 0.5 pg / well when indicated, then allowed to incubate at 37°C for 1 hour using the cell culture incubator. CAR-CD19-driven T cells (from Promab) were freshly thawed from previously aliquoted vials kept in liquid nitrogen and washed once with medium to remove DMSO. CAR19 T cells were then added to the 96-well plate where indicated, using a T cell:target (also known as target) ratio of 10:1 or 1:1, where the target was BT474 cells. On day 3, the 24 hour culture plate was harvested for analysis. Cell culture supernatant was removed and frozen at -20° for further interferon gamma measurement. Plates were gently washed x2 with RPMI 1640, then 100 pl medium was added to each well before performing the XTT cytotoxicity assay. On day 4, the 48 hour culture plate was harvested for analysis using the same procedure as that used for the 24 hour plate. XTT Cell Proliferation Assay (ATCC Cat # 30-101110 An aliquot of the XTT reagent and activating reagent was quickly thawed at 37 °C before use. Next, 0.1 ml of activating reagent was added to 5.0 ml of XTT reagent. Next, 50 µl of the activated XTT solution was added to each of the wells. The plate was placed in the cell culture incubator for 2-4 hours and the color development was monitored. The absorbance of the plate was read at a wavelength of 450 nm. The % cell death (also known as cytotoxicity) was calculated as follows: % kill = [1-OD (experimental wells-corresponding number of T cells) / OD (tumor cells without T-cell medium)]X100 Interferon gamma concentration assay by ELISA A 96-well plate (Pierce, product #15041) was coated with 1.0 pg / ml mouse anti-human IFNγ (BD Pharmingen, Cat #551221) in 0.1 M carbonate buffer, pH 9.5, overnight at 4 °C The plate was blocked with 0.3% non-fat dry milk solution in tris buffered saline (TBS) using 200 pl / well for 1 hour at room temperature. The plate was washed x3 with wash buffer (lx TBS / Tween: 0.1 M Tris, 0.5 M NaCl, 0.05% Tween 20). 100 μl of culture supernatant from the 24 hour or 48 hour culture plates (see above) was added to the ELISA plate. Recombinant human IFNγ (Thermo Fisher, Cat # RIFNG100) was also titrated on the same plate from 300 ng / ml with 3x serial dilutions down to 2 pg / ml to generate a standard curve. The plate was then incubated for 1 hour at room temperature. Dilution buffer was 1x TBS (0.1 M Tris, 0.5 M NaCl) plus 1% BSA. The plate was washed x3 with wash buffer. Biotinylated mouse anti-human IFNγ (BD Pharmingen, Cat #554550) was added at a concentration of 1 pg / ml and the plate was incubated at room temperature for 1 hour. The plate was washed x3 again with wash buffer. HRP-conjugated streptavidin (Thermo Fisher, Cat #21130) was added at a 1:2000 dilution of the stock, adding 100 pl per well. The plate was then incubated for 1 hour at room temperature in the dark. The plate was washed x3 again with wash buffer. I know added 100 pl per well of 1-Step Ultra TMB-ELISA Developing Solution (Thermo Fisher, Cat #34028) per well. The plate was read at a wavelength of 405nm when the color developed sufficiently. 2. Analysis of CAR19 T Cells Targeting 293-CD20 Cells by CD20-Binding Fusion Proteins 293 cells expressing CD20 were used as target cells and analyzed using the same XTT assay as described above. 3. Analysis of CAR19 T Cells Targeting A431 Cells by Fusion Proteins that Bind to EGFR A431 cells were used as target cells expressing EGFR and assayed using the same XTT assay described above. Results Summary IFNγ ELISA results at 24 hours for fusion protein construct #42 are shown in Figure 46 (10:1 effector:target ratio) and Figure 47 (1:1 effector:target ratio). . The increase in IFNγ concentration in both cases was >2-fold higher than background. Summary IFNγ ELISA results at 24 hours for construct #83 are shown in Figure 68A (10:1 effector:target ratio) and Figure 68B (2:1 effector:target ratio). Summary IFNγ ELISA results at 48 hours for fusion protein construct #83 are shown in Figure 68C (10:1 effector:target ratio) and Figure 68D (2:1 effect:target ratio). . Summary IFNγ ELISA results at 24 hours for construct #33-4 are shown in Figure 70 (2:1 target effect ratio). Figure 48 shows summary XTT cytotoxicity results for 10:1 effecton target ratio after 48 hours with construct #42 fusion protein and BT474 cells, showing >3-fold increase in cytotoxicity over background. . These results demonstrate that addition of the fusion protein from construct #42 successfully redirected CAR19 T cell targeting activity to kill a Her2-positive (and CD19-negative) cell. Additional IFNγ concentration controls are provided in Figures 49 and 50. Figure 70A shows summary XTT cytotoxicity results for 10:1 effecton target ratio after 48 hours with construct #83 fusion protein and 293-CD20 cells. Figure 70B shows summary XTT cytotoxicity results for the 2:1 effecton target ratio after 48 hours with the fusion protein from construct #83 and the 293-CD20 cells. A negative value indicates active cell growth throughout the course of the assay. These results demonstrate that the addition of the fusion protein (#83) successfully redirected CAR19 T cell targeting activity to kill a CD20-positive (and CD19-negative) cell by fusion of the anti- -CD20 scFv-CD19. Figure 71A shows summary XTT cytotoxicity results for 10:1 effector target ratio after 24 hours with fusion protein from constructs #33+#4 and A4321 cells. Figure 71B shows summary XTT cytotoxicity results for the 2:1 effector target ratio after 24 hours with the fusion protein from constructs #33 + #4 and A4321 cells. These results demonstrate that addition of the fusion protein (of construct #33 + #4, co-expressed) successfully redirected CAR19 T-cell targeting activity to kill an EGFR-positive (and CD19-) cell. negative) through the anti-EGFR-CD19 protein fusion. Figure 76A shows the expression and secretion of fusion protein construct #42 secreted from transfected Jurkat cells stably expressing a CAR CD19 construct (SEQ ID NO: 71: 1-tagged CAR-19 FMC63 construct). Detection of fusion protein secretion was performed by ELISA procedures described herein using FMC63 antibody to capture and HRP-conjugated anti-His antibody to detect. Figure 76B shows CAR19-mediated cytotoxicity redirected to HER2+ cells by CAR19 T cell secretion of fusion protein encoded by construct #42. 1x104 BT474 HER2+ cells were plated in each well of a plate. 12-well cell culture. The Jurkat-n stable line 0 71 with or without #42 inserted was added to wells containing BT474 cells in a 2:1 ratio for cytotoxicity analysis using the XTT assay. The assay was performed after 24 hours of co-culture of the T cells with the BT474 cells. Positive controls for the assay were the use of purified fusion protein from fusion protein bridging of construct #42 with Jurkat-71, and the use of purified fusion protein from fusion protein bridging of construct #42 with Jurkat-71. 42 with CAR19 T cells (Promab). Jurkat cells stably transfected with CAR19 construct #71 and then transiently transfected with construct #42 were able to secrete the encoded #42 fusion protein and mediate redirected killing of BT474 HER2+ cells. EXAMPLE 9 Analysis of Constitutive and Inducible Promoters in Jurkat Cells Methods Jurkat cells were grown in RPMI medium containing 10% Fetal Bovine Serum. (Gibco) and transfected using the Invitrogen Neon electroporation system as follows. All steps were performed at room temperature. Approximately 1.4x10 7Cells were centrifuged at 1000 rpm for 3 minutes. The supernatant was removed and the cells washed twice with PBS without calcium and magnesium (Gibco) and then centrifuged as above. Cells were resuspended in 1.3 ml of resuspension buffer R, provided in the Neon Transfection System kit, 100 pl (cat. no. MPK10096). 100 µl of the cell suspension containing approximately 10 6 Jurkat cells were used for each of the electroporations. A maximum volume of 10 μl for each DNA construct (minimum DNA concentration 0.73 pg / μl, maximum DNA concentration 1.48 pg / μl) was added to a 1.5 ml tube prior to cell distribution. The mixture was gently mixed and stopped at a tip of the Neon. Cells plus DNA mix were electroporated at the 1600 volt, 10 ms, 3-pulse setting in the Neon electroporation tubes filled with 3 mL E2 electrolyte buffer, provided in the Neon Transfection System kit. Cells were then placed in 2 mL RPMI / 10% FBS in a 6-well plate and incubated overnight at 37°C and 5% CO. 2 . On day 2, cells from each well were pipetted up and down and transferred to 2 wells of a 12-well plate (1 mL each). One well remained unstimulated and the other well stimulated with PMA (50 ng / ml) and ionomycin (1 pg / ml) for various periods of time. GFP reporter expression was read in the FL1 channel by a Flow Cytometer (Accuri, BD Biosystems) at 6 h, 18 h or 48 h. The activation state of the cells was determined using anti-human CD69 staining (Browning, J.L et al. 1997. J. Immunol. 159:3288-3298). The following constructs were evaluated: CMV-tGFP promoter (SEQ ID NO: 266); human CD69-tGFP promoter (SEQ ID NO: 246); human TNFalpha promoter-tGFP (SEQ ID NO: 247); and NFAT element x 6 promoter-tGFP (SEQ ID NO: 249). Electroporation without DNA was used as a control. Flow cytometry was performed using 5xl0 5 cells / test, blocked in FL1 to detect tGFP. Anti-CD69-PE conjugated antibody was used at 10 μl / test in 100 μl (BD Biosystems). Fluorescent dye PE (phycoerythrin) conjugated antibody to CD69 was read in the FL2 channel. The FACS buffer was PBS containing 1% BSA and 0.1% Sodium Azide. After a final wash, cells were fixed in 2% paraformaldehyde. Results As shown in Figures 61B and 61D, the constitutive CMV promoter was modestly impacted by Jurkat cell activation, with approximately 4% more cells present at the tGFP gate at increased MFI. However, constitutive activation was sufficient, as shown by non-activated samples having 14.7-17.9% cells in the positive gate (see Figures 60A and 60C). For inducible promoters, cells were activated using PMA and lonomycin to mimic canonical T cell activation. Under these activation ("P+I") conditions the TNF promoter had a marked impact on MFI at 6 hours (see Figures 62A-D), and the CD69 promoter had a dramatic impact on both % positive cells as on MFI at 48 hours (see Figures 61A-61D). These findings were consistent with the known kinetics of TNF and CD69 upregulation after T cell activation, in that TNF has rapid but short-lived activation, while CD69 arises gradually and then remains elevated (Sareneva, T. et al 1998. Immunology 93:350-357; Browning, IL et al. 1997. J. Immunol. 159:3288-3298). CD69 cell surface expression shows upregulation at 18 hours continuing at 48 hours (see Figures 63A to 63B), in support of the CD69-tGFP promoter data. NFATx6 had a moderate impact at 6 hours only and appeared to be the weakest promoter shown here (see Figures 62A to 62D). The results are summarized in the following Table: promoter activation 6hr % 6hr MFI 18hr % 18hr MFI 48hr % 48hr MFI post post post constitutive CMV - 14.7 1.3 17.9 0.5 CMV + 19 1.6 22 1.1 Inducible TNF - 33.8 1.5 0.1 0.02 TNF + 39.3 2.2 0.1 0.60 NFAT0.60 NFAT0x02 - 4 NFAT0x02 + 5.6 0.7 0.1 0.025 CD69 - 20.5 0.6 7.6 1.3 CD69 + 24 1 16.3 3.4 %Pos refers to the percentage of cells in gate R2 (tGFP-positive) on FACS plots; MFI is the mean fluorescence of cells within gate R2 (number of cells x 10 6 ). Negative control cell cultures without DNA averaged a "%Pos" value of less than 0.5 and an "MFI" of less than 0.03. EXAMPLE 10 Analysis of Heteromeric Fusion Proteins Methods The co-expression of CD19-Dl+D2-huIgGFc (construct no. 29 described in Example 5) and Trastuzumab scFv (VH / VL)-huIgGFc (amino acid SEQ ID NO: 103; nucleotide SEQ ID NO: 303; construct #103) were tested in 293T cells. 293T cells were transfected using Lipofectamine 2000 with nucleotide sequences encoding construct #29 only or #29 plus #103; supernatants were harvested after 3 days. An ELISA plate was coated with mAb FMC63 for the detection of homodimers of construct #29 and with HER2-huIgGFc for the detection of heterodimers of construct #29 + #103. Supernatants were added to the coated plate and allowed to incubate for 1 hour. After washing, bound protein was detected using an HRP-conjugated anti-huIgG antibody to the homodimer of #29. The #29 + #103 heterodimer was detected via the binding of mAb FMC63 followed by HRP-conjugated mouse IgG antibody. Figure 77 shows co-transfectant construct #29 (expressing CD19-Dl+D2-huIgGFc) together with construct #103 (expressing Trastuzumab scFv (VH / VL)-huIgGFc) resulting in the formation of homodimers and a heterodimer, where one arm is CD19-Dl+D2-huIgGFc and the other arm is Trastuzumab scFv (VH / VL)-huIgGFc. Heterodimer formation was detected by capturing the complex using the ligand for Trastuzumab (Her2-Fc) and detection using the anti-CD19 mAb, FMC63. EXAMPLE 11 Visualization of Yeast CD19 v Variants As discussed in the disclosure, in some embodiments, CD19 can be used as a scaffold to produce CD19 variants that can bind to targets of interest. This example demonstrates the production of yeast display libraries to select for such CD19 variants. Visualization of Yeasts of! Wild Type CD19 Extracellular Domain The extracellular domain of human wild-type CD19 (amino acids 1-272) was genetically fused, either C-terminally or N-terminally to Aga2p, through a polypeptide linker. Fusion constructs, with C-terminal c-myc epitope tags, were expressed within the yeast Saccharomyces cerevisiae EBY100. Yeast expression of CD19 was assessed by flow cytometry after labeling with fluorescein-conjugated mouse anti-c-myc epitope antibody (Bethyl). Experiments were performed as described in Chao et al., isolating and engineering human antibodies using a yeast surface display. Nat. Protoc. 1, 755-768 (2006)). As shown in Figure 78A to 78B, the extracellular domain of wild-type CD19 was visualized effectively on the yeast surface as a fusion to Aga2p in the format Aga2p-linker-CD19 (FIG. 78A) or CD19-linker-Aga2p (FIG. 78B). CD19 ECD displayed in yeast binds efficiently to anti-CD19 monoclonal antibodies (fmAbs) Fusion constructs, with C-terminal c-myc epitope tags, were expressed within the yeast Saccharomyces cerevisiae EBY100. Yeast CD19 expression and antibody binding were assessed by flow cytometry after labeling with fluorescein-conjugated goat anti-c-myc epitope antibody as well as the indicated mouse monoclonal antibody, followed by anti-mouse antibody. conjugated with AlexaFluor647. Experiments were performed as described in Chao et al., isolating and engineering human antibodies using a yeast surface display. Nat. Protoc. ...

Claims

NOVELTY OF THE INVENTION CLAIMS 1. A cell comprising a constitutively expressed construct encoding a fusion protein comprising (a) an antigen-binding protein or fragment that binds to a tumor antigen; and (b) a polypeptide target for a cell-therapeutic agent, antibody, or antibody-drug conjugate.

2. The cell of claim 1, wherein the tumor antigen is a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA).

3. The cell of claim 1, wherein the tumor antigen is MART-1 / MelanA (MART-I), gplOO (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, pl5, CEA, p53, HEAs, HEAs, HEAs BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus EBVA antigens, human papillomavirus (HPV) E6 or E7 antigens, TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE, NY-ESOB, erb, Bpl pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, 5T4, 791, alpha-phenoprotein, beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, M0V18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2-associated protein\cyclophilin C-associated protein, TAAL6, TAG72, TLP, MUC16, IL13Ra2, FRo, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FÓLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalyl cyclase C, MUC-1, CFC1B, cadena alfa 3 de la integrina (de a3bl, una cadena receptora de laminin), TPS, CD19, CD20, CD22, CD30, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL-1 / CLEC12A, ROR1, Glypican 3 (GPC3), Mesothelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glucolípido F77, EGFRvIII, BCMA, GD-2, MY-ESO-1 o MAGE A3.

4. The cell of any one of claims 1-3, wherein the antigen-binding protein is a Type III fibronectin domain, a CD19 variant, a B cell-specific marker variant, or an antibody or fragment (e.g., scFv, Fv, or VHH).

5. The cell of any one of claims 1-4, wherein the cell therapeutic agent is a CAR-T cell, a CAR-NK cell, a TCR-T cell, a TIL cell, an allogeneic NK cell, or an autologous NK cell.

6. The cell of any one of claims 1-5, wherein the polypeptide target is a B cell-specific marker or fragment.

7. The cell of claim 6, wherein the cell-specific marker B is CD19, CD20, CD21, CD22, CD24, CD72, CD79a, CD79b, R0R1, BCMA or CD180.

8. The cell of any one of claims 1-7, wherein the fusion protein comprises the antigen-binding protein or fragment at the N-terminus and the polypeptide target at the C-terminus.

9. The cell of any one of claims 1-7, wherein the fusion protein comprises the antigen-binding protein or fragment at the C-terminus and the polypeptide target at the N-terminus.

10. The cell of any one of claims 1-9, wherein the cell is an immune cell or a tumor cell.

11. A cell comprising a constitutively expressed construct encoding a fusion protein comprising (a) a masked antigen-binding protein or fragment that binds to a tumor antigen; and (b) a polypeptide target for a cell-therapeutic agent, antibody, or antibody-drug conjugate.

12. The cell of claim 11, wherein the masked antigen-binding protein or fragment comprises a masking residue and a cleavage residue.

13. The cell of claim 12, wherein the scissile remnant is a substrate for a tumor-associated protease.

14. The cell of claim 12, wherein the scisdiole residue is a substrate for legumain, plasmin, TMPRSS-3 / 4, MMP-9, MT1-MMP, cathepsin, caspase, human neutrophil elastase, beta-secretase, matriptase, uPA or PSA.

15. The cell of any one of claims 12-14, wherein after excision of the excised remnant, the antigen-binding protein or fragment binds to the tumor antigen.

16. The cell of any one of claims 11-15, wherein the tumor antigen is a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA).

17. La célula de una cualquiera de las reivindicaciones 11-15, en la que el antígeno tumoral es MART-l / MelanA (MART-I), gplOO (Pmel 17), tirosinasa, TRP-1, TRP-2, MAGE-1, IMAGE-3, BAGE, GAGE-1, GAGE-2, pl5, CEA, p53, Ras, HER-2 / neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, antígenos del virus Epstein Barr EBVA, antígenos E6 o E7 de papilomavirus humano (HPV), TSP-180, MAGE-4, MAGE-5, IMAGE-6, RAGE, NY-ESO, erbB, pl85erbB2, pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2-associated protein\cyclophilin C-associated protein, TAAL6, TAG72, TLP, MUC16, IL13Ro2, FRo, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, F0LR1, endothelial receptor, STEAP1 SLC44A4, Nect¡na-4, AGS-16, guanalyl cyclase C, MUC-1, CFC1B, integrin alpha 3 chain (from a3bl, a laminin receptor chain), TPS, CD19, CD20, CD22, CD30, CD72, CD180, CD171 (LIGAN), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL-1 / CLEC12A, R0R1, Glypican 3 (GPC3), Mesothelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glycolipid F77, EGFRvIII, BCMA, GD-2, MY-ESO-1 or MAGE A3.

18. The cell of any one of claims 11-17, wherein the antigen-binding protein is a Type III fibronectin domain, a CD19 variant, a B cell-specific marker variant, or an antibody or fragment (e.g., scFv, Fv, or VHH).

19. The cell of any one of claims 11-18, wherein the cell therapeutic agent is a CAR-T cell, a CAR-NK cell, a TCR-T cell, a TIL cell, an allogeneic NK cell, or an autologous NK cell.

20. The cell of any one of claims 11-19, wherein the polypeptide target is a B cell-specific marker or fragment.

21. The cell of claim 20, wherein the B cell-specific marker is CD19, CD20, CD21, CD22, CD24, CD72, CD79a, CD79b, ROR1, BCMA or CD180.

22. The cell of any one of claims 11-21, wherein the The fusion protein comprises the antigen-binding protein or fragment at the N-terminus and the polypeptide target at the C terminus.

23. The cell of any one of claims 11-21, wherein the The fusion protein comprises the antigen-binding protein or fragment at the C-terminus and the polypeptide target at the N terminus.

24. The cell of any one of claims 11-23, wherein the cell is an immune cell or a tumor cell.

25. A cell comprising (i) an antigen-binding receptor comprising an antigen-binding domain that binds to a first tumor antigen, a transmembrane domain, and a cytosolic signaling domain, and (ii) an inducible expression construct encoding a fusion protein comprising (a) an antigen-binding protein or fragment that binds to a second tumor antigen; and (b) a polypeptide target for a cell-therapeutic agent, antibody, or antibody-drug conjugate.

26. The cell of claim 25, wherein the first tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin O, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prosthetic-specific antigen (PSA), PAP, NY-ESO-1, LAGE-1, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, CLL-1 / CLEC12A, ROR1, BCMA, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor or mesothelin.

27. The cell of claim 25 or 26, wherein the second tumor antigen is a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA).

28. La célula de una cualquiera de las reivindicaciones 25-27, en la que el segundo antigeno tumoral es MART-l / MelanA (MART-I), gplOO (Pmel 17), tirosinasa, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, pl5, CEA, p53, Ras, HER-2 / neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, antígenos del virus Epstein Barr EBVA, antígenos E6 o E7 de papilomavirus humano (HPV), TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE, NY-ESO, erbB, pl85erbB2, pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2-associated protein\cyclophilin C-associated protein, TAAL6, TAG72, TLP, MUC16, IL13Ra2, FRd, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FOLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalil cyclase C, MUC-1, CFC1B, cadena alfa 3 de la integrina (de a3bl, una cadena receptora de laminin), TPS, CD19, CD20, CD22, CD30, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL-1 / CLEC12A, ROR1, Glipicano 3 (GPC3), Mesotelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glucolípido F77, EGFRvIII, BCMA, GD-2, MY-ESO-1 o MAGE A3.

29. The cell of any one of claims 25-28, wherein the antigen-binding protein is a Type III fibronectin domain, a CD19 variant, a B cell-specific marker variant, or an antibody or fragment (e.g., scFv, Fv, or VHH).

30. The cell of any one of claims 25-29, wherein the cell therapeutic agent is a CAR-T cell, a CAR-NK cell, a TCR-T cell, a TIL cell, an allogeneic NK cell, or an autologous NK cell.

31. The cell of any one of claims 25-30, wherein the polypeptide target is a B cell-specific marker or fragment.

32. The cell of claim 31, wherein the B cell-specific marker is CD19, CD20, CD21, CD22, CD24, CD72, CD79a, CD79b, ROR1, BCMA or CD180.

33. The cell of any one of claims 25-32, wherein the fusion protein comprises the antigen-binding protein or fragment at the N-terminus and the polypeptide target at the C-terminus.

34. The cell of any one of claims 25-32, wherein the The fusion protein comprises the antigen-binding protein or fragment at the C-terminus and the polypeptide target at the N-terminus.

35. The cell of any one of claims 25-34, wherein the cell is an immune cell or a tumor cell.

36. A cell comprising (i) an antigen-binding receptor comprising an antigen-binding domain that binds to a first tumor antigen, a transmembrane domain, and a cytosolic signaling domain, and (ii) an inducible expression construct encoding a fusion protein comprising (a) a masked antigen-binding protein or fragment that binds to a second tumor antigen; and (b) a polypeptide target for a cell-therapeutic agent, antibody, or antibody-drug conjugate.

37. The cell of claim 36, wherein the masked antigen-binding protein or fragment comprises a masking residue and a cleavage residue.

38. The cell of claim 37, wherein the scissile remnant is a substrate for a tumor-associated protease.

39. The cell of claim 37, wherein the cleavage residue is a substrate for legumain, plasmin, TMPRSS-3 / 4, MMP-9, MT1-MMP, cathepsin, caspase, human neutrophil elastase, beta-secretase, matriptase, uPA or PSA.

40. The cell of any one of claims 37-39, wherein after excision of the excised remnant, the antigen-binding protein or fragment binds to the second tumor antigen.

41. The cell of any one of claims 36-40, wherein the first tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin p, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-la, p53, prosterna, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, CLL-1 / CLEC12A, ROR1, BCMA, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin growth factor (IGF)-I, IGF-II, IGF-I receptor or mesothelin.

42. The cell of any one of claims 36-41, wherein the second tumor antigen is a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA).

43. La célula dé una cualquiera de las reivindicaciones 36-42, en la que el segundo antígeno tumoral es MART-l / MelanA (MART-I), gplOO (Pmel 17), tirosinasa, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, pl5, CEA, p53, Ras, HER-2 / neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, antígenos del virus Epstein Barr EBVA, antígenos E6 o E7 de papilomavirus human (HPV), TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE, NY-ESO, erbB, pl85erbB2, pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-7.1 K beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2-associated protein\cyclophilin C-associated protein, TAAL6, TAG72, TLP, MUC16, IL13RO2, FRo, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FOLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalil cyclase C, MUC-1, CFC1B, cadena alfa 3 de la integrina (de a3bl, una cadena receptora de laminin), TPS, CD19, CD20, CD22, CD30, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL-1 / CLEC12A, ROR1, Glipicano 3 (GPC3), Mesotelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glucolípido F77, EGFRvIII, BCMA, GD-2, MY-ESO-1 o MAGE A3.

44. The cell of any one of claims 36-43, wherein the antigen-binding protein is a Type III fibronectin domain, a CD19 variant, a B cell-specific marker variant, or an antibody or fragment (e.g., scFv, Fv, or VHH).

45. The cell of any one of claims 36-44, wherein the cell therapeutic agent is a CAR-T cell, a CAR-NK cell, a TCR-T cell, a TIL cell, an autogenic NK cell, or an autologous NK cell.

46. ​​The cell of any one of claims 36-45, wherein the polypeptide target is a B cell-specific marker or fragment.

47. The cell of claim 46, wherein the B cell-specific marker is CD19, CD20, CD21, CD22, CD24, CD72, CD79a, CD79b, ROR1, BCMA or CD180.

48. The cell of any one of claims 36-47, wherein the The fusion protein comprises the antigen-binding protein or fragment at the N-terminus and the polypeptide target at the C terminus.

49. The cell of any one of claims 36-47, wherein the The fusion protein comprises the antigen-binding protein or fragment at the C-terminus and the polypeptide target at the N terminus.

50. The cell of any one of claims 36-49, wherein the cell is an immune cell or a tumor cell.

51. A fusion protein comprising (a) an antigen-binding protein or fragment that binds to a tumor antigen; and (b) a polypeptide target for a cell-therapeutic agent, antibody, or antibody-drug conjugate.

52. The fusion protein of claim 51, wherein the tumor antigen is a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA).

53. The fusion protein of claim 51, wherein the tumor antigen is MART-l / MelanA (MART-I), gplOO (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, CEA, Ras, ppl53 HER-2 / neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus EBVA antigens, human papillomavirus (HPV) E6 or E7 antigens, TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE-ERB, NYB, pl85erbB2, pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, Tg-72, 714 alpha-fetoprotein, beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2-associated protein\cyclophilin C-associated protein, TAAL6, TAG72, TLP, MUC16, IL13Ra2, FRo, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FOLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalil cyclase C, MUC-1, CFC1B, cadena alfa 3 de la integrina (de a3bl, una cadena receptora de laminin), TPS, CD19, CD20, CD22, CD30, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL-1 / CLEC12A, ROR1, Glipicano 3 (GPC3), Mesotelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glucolípido F77, EGFRvIII, BCMA, GD-2, MY-ESO-1 o MAGE A3.

54. The fusion protein of any one of claims 51-53, wherein the antigen-binding protein is a Type III fibronectin domain, a CD19 variant, a B-cell-specific marker variant, or an antibody or fragment (e.g., scFv, Fv, or VHH).

55. The fusion protein of any one of claims 51-54, wherein the cell therapeutic agent is a CAR-T cell, a CAR-NK cell, a TCR-T cell, a TIL cell, an allogeneic NK cell, or an autologous NK cell.

56. The fusion protein of any one of claims 51-55, wherein the polypeptide target is a B cell-specific marker or fragment.

57. The fusion protein of claim 56, wherein the B cell-specific marker is CD19, CD20, CD21, CD22, CD24, CD72, CD79a, CD79b, ROR1, BCMA or CD180.

58. The fusion protein of any one of claims 51-57, wherein the fusion protein comprises the antigen-binding protein or fragment at the N-terminus and the polypeptide target at the C-terminus.

59. The fusion protein of any one of claims 51-57, wherein the fusion protein comprises the antigen-binding protein or fragment at the C-terminus and the polypeptide target at the N-terminus.

60. A fusion protein comprising (a) a protein or fragment of (b) a masked antigen binding that binds to a tumor antigen; and (b) a polypeptide target for a cell-mediated therapeutic agent, antibody, or antibody-drug conjugate.

61. The fusion protein of claim 60, wherein the masked antigen-binding protein or fragment comprises a masking residue and a cleavable residue.

62. The fusion protein of claim 61, wherein the cleavable moiety is a substrate for a tumor-associated protease.

63. The fusion protein of claim 61, wherein the cleavable residue is a substrate for legumain, plasmin, TMPRSS-3 / 4, MMP-9, MT1-MMP, cathepsin, caspase, human neutrophil elastase, beta-secretase, matriptase, uPA or PSA.

64. The fusion protein of any one of claims 61-63, wherein after cleavage of the cleavable remainder, the antigen-binding protein or fragment binds to the tumor antigen.

65. The fusion protein of any one of claims 60-64, wherein the tumor antigen is a tumor-specific antigen (TSA) or a tumor-associated antigen (TAA).

66. La proteína de fusion de una cualquiera de las reivindicaciones 60-64, en la que el antígeno tumoral es MART-l / MelanA (MART-I), gplOO (Pmel 17), tirosinasa, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, pl5, CEA, p53, Ras, HER-2 / neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, antígenos del virus Epstein Barr EBVA, antígenos E6 o E7 de papilomavirus humano (HPV), TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE, NY-ESO, erbB, pl85erbB2, pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2-associated protein\cyclophilin C-associated protein, TAAL6, TAG72, TLP, MUC16, IL13RO2, FRa, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FOLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalil cyclase C, MUC-1, CFC1B, cadena alfa 3 de la integrina (de a3bl, una cadena receptora de laminin), TPS, CD19, CD20, CD22, CD30, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL-1 / CLEC12A, ROR1, Glipicano 3 (GPC3), Mesotelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glucolípido F77, EGFRvIII, BCMA, GD-2, MY-ESO-1 o MAGE A3.

67. The fusion protein of any one of claims 60-66, wherein the antigen-binding protein is a Type III fibronectin domain, a CD19 variant, a B-cell-specific marker variant, or an antibody or fragment (e.g., scFv, Fv, or VHH).

68. The fusion protein of any one of claims 60-67, wherein the cell therapeutic agent is a CAR-T cell, a CAR-NK cell, a TCR-T cell, a TIL cell, an allogeneic NK cell, or an autologous NK cell.

69. The fusion protein of any one of claims 60-68, wherein the polypeptide target is a B cell-specific marker or fragment.

70. The fusion protein of claim 69, wherein the B cell-specific marker is CD19, CD20, CD21, CD22, CD24, CD72, CD79a, CD79b, ROR1, BCMA or CD180.

71. The fusion protein of any one of claims 60-70, wherein the fusion protein comprises the antigen-binding protein or fragment at the N-terminus and the polypeptide target at the C-terminus.

72. The fusion protein of any one of claims 60-70, wherein the fusion protein comprises the antigen-binding protein or fragment at the C-terminus and the polypeptide target at the N-terminus.

73. An immune cell comprising (i) an antigen-binding receptor, wherein the antigen-binding receptor comprises an antigen-binding domain, a transmembrane domain, and a cytosolic signaling domain, and (ii) an inducible expression construct.

74. The immune cell of claim 73, wherein the inducible expression construct comprises a gene of interest.

75. The immune cell of claim 74, wherein the inducible expression construct further comprises a promoter operatively linked to the gene of interest.

76. The immune cell of claim 75, wherein the binding of an antigen to the antigen-binding region activates the signaling domain.

77. The immune cell of claim 75, wherein the activated signaling domain induces expression of the gene of interest.

78. The immune cell of any one of claims 73-77, wherein The immune cell is a T cell, an NK cell, or a TIL.

79. The immune cell of any one of claims 73-78, wherein The antigen-binding region binds to a first tumor antigen.

80. The immune cell of claim 79, wherein the gene of interest is a fusion protein comprising an antibody, or antigen-binding fragment, and a heterologous polypeptide.

81. The immune cell of claim 80, wherein the antibody, or antigen-binding fragment, binds to a second tumor antigen.

82. The immune cell of claim 81, wherein the heterologous polypeptide is an antigen for a CAR-T cell.

83. The immune cell of claim 82, wherein the heterologous peptide is CD19, or a fragment thereof.

84. An immune cell, comprising (i) an antigen-binding receptor comprising an antigen-binding domain that binds to a first tumor antigen, a transmembrane domain, and a cytosolic signaling domain, and (ii) an inducible expression construct encoding a fusion protein comprising (a) an antibody, or an antigen-binding fragment thereof, that binds to a second tumor antigen, and (b) CD19, or a fragment thereof.

85. The immune cell of claim 84, wherein the antigen-binding domain comprises a scFv, VHH or T cell receptor that binds to the first tumor antigen.

86. The immune cell of claim 84 or 85, wherein the first tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin O, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-1, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, receptor of IGF-I or mesothelin.

87. The immune cell of any one of claims 84-86, wherein the fusion protein comprises an scFv or VHH that binds to the second tumor antigen and CD19 or a fragment thereof.

88. The immune cell of any one of claims 84-87, wherein the second tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin O, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-1, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor or mesothelin.

89. The immune cell of any one of claims 84-88, wherein the inducible expression construct comprises a promoter operatively linked to a nucleotide encoding the fusion protein.

90. The immune cell of claim 89, wherein the promoter is an IL-2 promoter, a cell surface protein promoter (e.g., CD69 promoter), a cytokine promoter (e.g., TNF promoter), a cell activation promoter (e.g., CTLA4 0X40, CD40L), or a cell surface adhesion protein promoter (e.g., VLA-1 promoter).

91. The immune cell of any one of claims 84-90, wherein the immune cell is a T cell, an NK cell or a TIL.

92. The immune cell of any one of claims 84-91, wherein the cell comprises an expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and the inducible expression construct.

93. The immune cell of any one of claims 84-91, wherein the cell comprises a first expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and comprising a second expression vector comprising the inducible expression construct.

94. The immune cell of any one of claims 84-93, wherein upon binding of the antigen-binding region to the first tumor antigen, the signaling domain induces expression of the fusion protein.

95. An immune cell, comprising (i) an antigen-binding receptor, wherein the antigen-binding receptor comprises an antigen-binding domain that binds to a first tumor antigen, a transmembrane domain, and a cytosolic signaling domain and (ii) an inducible expression construct encoding a fusion protein comprising (a) an antibody that binds to a second tumor antigen and (b) a B-cell-specific marker, or a fragment thereof.

96. The immune cell of claim 95, wherein the specific marker for B cells is CD19, CD20, CD21, CD22, CD24 or BCMA.

97. The immune cell of claim 95 or 96, wherein the antigen-binding domain comprises a scFv, VHH or T cell receptor that binds to the first tumor antigen.

98. The immune cell of any one of claims 95-97, wherein the first tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin P, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-α, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I, BCMA or mesothelin receptor.

99. The immune cell of any one of claims 95-98, wherein the fusion protein comprises an scFv or VHH that binds to the second tumor antigen and a B cell-specific marker.

100. The immune cell of any one of claims 95-99, wherein the second tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin p, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-1, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor, BCMA or mesothelin.

101. The immune cell of any one of claims 95-100, wherein the inducible expression construct comprises a promoter operatively linked to a nucleotide encoding the fusion protein.

102. The immune cell of claim 101, wherein the promoter is an IL-2 promoter, a cell surface protein promoter (e.g., CD69 promoter), a cytokine promoter (e.g., TNF promoter), a cell activation promoter (e.g., CTLA4 0X40, CD40L), or a cell surface adhesion protein promoter (e.g., VLA-1 promoter).

103. The immune cell of any one of claims 95-102, wherein the immune cell is a T cell, an NK cell or a TIL.

104. The immune cell of any one of claims 95-103, wherein the cell comprises an expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and the inducible expression construct.

105. The immune cell of any one of claims 95-103, wherein the cell comprises a first expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and comprising a second expression vector comprising the inducible expression construct.

106. The immune cell of any one of claims 95-105, wherein upon binding of the antigen-binding region to the first tumor antigen, the signaling domain induces expression of the fusion protein.

107. An immune cell, comprising (i) an antigen-binding receptor comprising an antigen-binding domain that binds to a tumor antigen, a transmembrane domain, and a cytosolic signaling domain, and (ii) an inducible expression construct encoding a fusion protein comprising a cytokine and CD19, or a fragment of the same.

108. The immune cell of claim 107, wherein the cytokine is IFNa, IFN0, IFNy, IL-1, IL-2, IL-7, IL-12, IL-15, IL-21, IL-36, TNF, LTa, GM-CSF or G-CSF.

109. The immune cell of claim 107 or 108, wherein the antigen-binding domain comprises a scFv, VHH or T cell receptor that binds to the tumor antigen.

110. The immune cell of any one of claims 107-109, wherein the tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin O, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-la, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor, BCMA or mesothelin.

111. The immune cell of any one of claims 107-110, wherein the inducible expression construct comprises a promoter operatively linked to a nucleotide encoding the fusion protein.

112. The immune cell of claim 111, wherein the promoter is an IL-2 promoter, a cell surface protein promoter (e.g., CD69 promoter), a cytokine promoter (e.g., TNF promoter), a cell activation promoter (e.g., CTLA4 0X40, CD40L), or a cell surface adhesion protein promoter (e.g., VLA-1 promoter).

113. The immune cell of any one of claims 107-112, wherein the immune cell is a T cell, an NK cell or a TIL.

114. The immune cell of any one of claims 107-113, wherein the cell comprises an expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and the inducible expression construct.

115. The immune cell of any one of claims 107-113, wherein the cell comprises a first expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and comprising a second expression vector comprising the inducible expression construct.

116. The immune cell of any one of claims 107-115, wherein upon binding of the antigen-binding region to the tumor antigen, the signaling domain induces expression of the fusion protein.

117. An immune cell, comprising (i) an antigen-binding receptor comprising an antigen-binding domain that binds to a tumor antigen, a domain of transmembrane and a cytosolic signaling domain, and (i) an inducible expression construct that encodes a cytotoxin.

118. The immune cell of claim 117, wherein the cytotoxin is diphtheria toxin or ricin.

119. The immune cell of claim 117 or 118, wherein the antigen-binding domain comprises a scFv, VHH or T cell receptor that binds to the tumor antigen.

120. The immune cell of any one of claims 117-119, wherein the tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin p, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-1, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor, BCMA or mesothelin.

121. The immune cell of any one of claims 117-120, wherein the inducible expression construct comprises a promoter operatively linked to a nucleotide encoding the cytotoxin.

122. The immune cell of claim 121, wherein the promoter is an IL-2 promoter, a cell surface protein promoter (e.g., CD69 promoter), a cytokine promoter (e.g., TNF promoter), a cell activation promoter (e.g., CTLA4 0X40, CD40L), or a cell surface adhesion protein promoter (e.g., VLA-1 promoter).

123. The immune cell of any one of claims 117-122, wherein the immune cell is a T cell, an NK cell or a TIL.

124. The immune cell of any one of claims 117-123, wherein the cell comprises an expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and the inducible expression construct.

125. The immune cell of any one of claims 117-123, wherein the cell comprises a first expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and comprising a second expression vector comprising the inducible expression construct.

126. The immune cell of any one of claims 117-125, wherein upon binding of the antigen-binding region to the tumor antigen, the signaling domain induces expression of the cytotoxin.

127. An immune cell, comprising (i) an antigen-binding receptor that It comprises an antigen-binding domain that binds to a first tumor antigen, a transmembrane domain and a cytosolic signaling domain, and (i) an inducible expression construct encoding a variant of CD19 or antigen-binding fragment thereof, which binds to a second tumor antigen.

128. The immune cell of claim 127, wherein the antigen-binding domain comprises a scFv, VHH or T cell receptor that binds to the first tumor antigen.

129. The immune cell of claim 127 or 128, wherein the first tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin P, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-α, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I, BCMA or mesothelin receptor.

130. The immune cell of any one of claims 127-129, wherein the CD19 variant comprises an amino acid substitution, relative to wild-type CD19, of an amino acid residue in the CD19 ECD, or in one or both C2-type Ig domains.

131. The immune cell of any one of claims 127-130, wherein the second tumor antigen is a glioma-associated antigen, carcinoembryonic antigen (CEA), human chorionic gonadotropin I3, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-α, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor, BCMA or mesothelin.

132. The immune cell of any one of claims 127-131, wherein the inducible expression construct comprises a promoter operatively linked to a nucleotide encoding the CD19 variant.

133. The immune cell of claim 132, wherein the promoter is an IL-2 promoter, a cell surface protein promoter (e.g., CD69 promoter), a cytokine promoter (e.g., TNF promoter), a cell activation promoter (e.g., CTLA4 0X40, CD40L), or a cell surface adhesion protein promoter (e.g., VLA-i promoter)- 134. The immune cell of any one of claims 127-133, wherein the immune cell is a T cell, an NK cell or a TIL.

135. The immune cell of any one of claims 127-134, wherein the cell comprises an expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and the inducible expression construct.

136. The immune cell of any one of claims 127-134, wherein the cell comprises a first expression vector comprising a nucleotide sequence encoding the antigen-binding receptor and comprising a second expression vector comprising the inducible expression construct.

137. The immune cell of any one of claims 127-136, wherein upon binding of the antigen-binding region to the first tumor antigen, the signaling domain induces expression of the CD19 variant.

138. A fusion protein, comprising (a) an antibody, or antigen-binding fragment thereof, that binds to a tumor antigen, and (b) CD19, or a fragment thereof.

139. The fusion protein of claim 138, wherein the tumor antigen is a glioma-associated antigen, cardiac embryonic antigen (CEA), human chorionic gonadotropin p, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-la, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, receptor of IGF-I, BCMA or mesothelin.

140. The fusion protein of claim 138 or 139, wherein the fusion protein comprises a tumor antigen-binding scFv or VHH and CD19 or a fragment thereof.

141. A fusion protein comprising (a) an antibody or fragment that binds to a tumor antigen, and (b) a B-cell specific marker, or a fragment thereof.

142. The fusion protein of claim 141, wherein the B cell-specific marker is CD19, CD20, CD21, CD22, CD24 or BCMA.

143. The fusion protein of claim 141 or 142, wherein the tumor antigen is a glioma-associated antigen, cardiac embryonic antigen (CEA), human chorionic gonadotropin p, alpha-fetoprotein (AFP), lectin-reactive AFP, thyroglobulin, RAGE-1, MN-CA IX, human telomerase reverse transcriptase, RUI, RU2 (AS), intestinal carboxylesterase, mut hsp70-2, M-CSF, prostase, prostate-specific antigen (PSA), PAP, NY-ESO-1, LAGE-la, p53, prosteine, PSMA, Her2 / neu, survivin and telomerase, prostate carcinoma tumor antigen-1 (PCTA-1), MAGE, ELF2M, neutrophil elastase, ephrin B2, CD22, insulin-like growth factor (IGF)-I, IGF-II, IGF-I receptor, BCMA or mesothelin.

144. The fusion protein of any one of claims 141-143, wherein the fusion protein comprises a tumor antigen-binding scFv or VHH and a B-cell-specific marker or fragment thereof.

145. A fusion protein comprising a cytokine and CD19, or a fragment thereof.

146. The fusion protein of claim 145, wherein the cytokine is IFNo, IFNP, IFNy, IL-1, IL-2, IL-7, IL-12, IL-15, IL-21, IL-36, TNF, LTo, GM-CSF or G-CSF.

147. A method for treating a subject having a tumor, comprising administering to the subject the cell of any one of claims 1-50 or 84-94.

148. The method of claim 147, wherein the tumor expresses the first tumor antigen and the second tumor antigen.

149. The method of claim 147 or 148, wherein the tumor does not express CD19.

150. The method of any one of claims 147-149, wherein the cell binds to the first tumor antigen.

151. The method of claim 150, wherein the binding of the cell to the first tumor antigen induces the expression of the fusion protein.

152. The method of claim 151, wherein the fusion protein is secreted from the cell.

153. The method of claim 152, wherein the fusion protein is bound to the second tumor antigen.

154. The method of any one of claims 147-153, further comprising administering an antibody, an antibody-drug conjugate, or a CAR-T cell to the subject, wherein the antibody, antibody-drug conjugate, or CAR-T cell targets CD19.

155. The method of claim 154, wherein upon administration, the antibody, antibody-drug conjugate, or CAR-T cell binds to the fusion protein comprising CD19.

156. The method of claim 155, wherein the binding of the CAR-T cell to the fusion protein comprising CD19 induces tumor destruction.

157. A method for treating a subject having a tumor, comprising administering to the subject the cell of any one of claims 1-50 or 95-106.

158. The method of claim 157, wherein the tumor expresses the first tumor antigen and the second tumor antigen.

159. The method of claim 157 or 158, wherein the tumor does not express the specific marker for B cells.

160. The method of any one of claims 157-159, wherein the cell binds to the first tumor antigen.

161. The method of claim 160, wherein the binding of the cell to the first tumor antigen induces the expression of the fusion protein.

162. The method of claim 161, wherein the fusion protein is secreted from the cell.

163. The method of claim 162, wherein the fusion protein is bound to the second tumor antigen.

164. The method of any one of claims 157-163, further comprising administering an antibody, an antibody-drug conjugate, or a CAR-T cell to the subject, wherein the antibody, antibody-drug conjugate, or CAR-T cell targets the specific B-cell marker.

165. The method of claim 164, wherein after administration, the antibody, antibody-drug conjugate or CAR-T cell binds to the fusion protein comprising the B cell-specific marker.

166. The method of claim 165, wherein the binding of the CAR-T cell to the fusion protein comprising the B cell-specific marker induces tumor destruction.

167. A method for treating a subject having a tumor, comprising administering to the subject the cell of any one of claims 1-50 or 127-137.

168. The method of claim 167, wherein the tumor expresses the first tumor antigen and the second tumor antigen.

169. The method of claim 167 or 168, wherein the cell binds to the first tumor antigen.

170. The method of claim 169, wherein the binding of the cell to the first tumor antigen induces the expression of the CD19 variant.

171. The method of claim 170, wherein the CD19 variant is secreted from the cell.

172. The method of claim 171, wherein the CD19 variant binds to the second tumor antigen.

173. The method of any one of claims 167-172, further comprising administering an antibody, an antibody-drug conjugate, or a CAR-T cell to the subject, wherein the antibody, antibody-drug conjugate, or CAR-T cell is fixed as objective CD19.

174. The method of claim 173, wherein, upon administration, the antibody, antibody-drug conjugate, or CAR-T cell binds to the CD19 variant.

175. The method of claim 174, wherein the binding of the CAR-T cell to the CD19 variant induces tumor destruction.

176. A method for treating a subject having a tumor, comprising administering to the subject the fusion protein of any one of claims 51-72 or 138-140.

177. The method of claim 176, wherein the tumor expresses the tumor antigen.

178. The method of claim 176 or 177, wherein the tumor does not express CD19.

179. The method of any one of claims 176-178, wherein, after administration, the fusion protein binds to the tumor antigen.

180. The method of any one of claims 176-179, further comprising administering an antibody, an antibody-drug conjugate, or a CAR-T cell to the subject, wherein the antibody, antibody-drug conjugate, or CAR-T cell targets CD19.

181. The method of claim 180, wherein upon administration, the antibody, antibody-drug conjugate or CAR-T cell binds to the fusion protein comprising CD19.

182. The method of claim 181, wherein the binding of the CAR-T cell to the fusion protein comprising CD19 induces tumor destruction.

183. A method for treating a subject having a tumor, comprising administering to the subject the fusion protein of any one of claims 51-72 or 141-144.

184. The method of claim 183, wherein the tumor expresses the tumor antigen.

185. The method of claim 183 or 184, wherein the tumor does not express the specific marker for B cells.

186. The method of any one of claims 183-185, wherein, after administration, the fusion protein binds to the tumor antigen.

187. The method of any one of claims 183-186, further comprising administering an antibody, an antibody-drug conjugate, or a CAR-T cell to the subject, wherein the antibody, antibody-drug conjugate, or CAR-T cell targets the specific B-cell marker.

188. The method of claim 187, wherein after administration, the antibody, antibody-drug conjugate or CAR-T cell binds to the fusion protein comprising the B cell-specific marker.

189. The method of claim 188, wherein the binding of the CAR-T cell to the fusion protein comprising the B-cell specific marker induces tumor destruction.

190. An immune cell, comprising (i) a first antigen-binding receptor, wherein the antigen-binding receptor comprises an antigen-binding domain, a transmembrane domain, and a cytoplasmic signaling domain, and (ii) an inducible expression construct, whereby the cytoplasmic transmembrane and / or domain includes a cytoplasmic and / or transmembrane domain of a PDGF receptor (e.g., PDGFR-alpha or PDGFR-beta), an IL-12 receptor cell (e.g., IL-12R-betal / IL-12beta2), an IL-6 receptor alpha cell, a leptin receptor, a of prolactin, a receptor coupled to G protein that is linked to the JAK / STAT pathway (e.g., AGTR-1. 5-HT2A, PAR, PAR3, PAR4, Bradiquinina-RB2, PAFR, alpha adrenergic receptors, CXCR4, CCR2, CCR5, CCR1), a receptor of IL-12 (e.g., IL-23R, IL-27R), an IL-10 receptor, an IL-6 receptor (e.g., IL-HR, CNTFR, LIFR, OSMR, GCSFR, IL-31R, CTNFR), a family of gamma receptors (e.g., IL-2R, IL-4R, IL-7R, IL-9R, IL-13R, IL-15R, IL-21R and the related receptor TSLPR), a beta-caden receptor (e.g., IL-3, IL-5R, GM-CSFR), a homodimonic hormone receptor (e.g., GHR, TpoR, EpoR), an Insulin-R, EGFR / ERbB receptor, SCF-R / c-Kit, M-CSFR, FGF receptor (p. ej., FGF 1-4 receptor), EphA4, TrkB, Tie2, a VEGF receptor, Mer, HGFR / c-MET or a Type I / II interferon receptor.

191. The immune cell of claim 190, wherein the inducible expression construct encodes a second antigen-binding receptor.

192. The immune cell of claim 190 or 191, wherein the binding of a first antigen to the first antigen-binding region activates the signaling domain.

193. The immune cell of any one of claims 190-192, wherein activation of the signaling domain does not induce cytotoxicity of a target cell.

194. The immune cell of claim 193, wherein activation of the signaling domain induces expression of the second antigen-binding receptor.

195. The immune cell of claim 194, wherein the binding of a second antigen to the second antigen-binding region induces cytotoxicity of a target cell.

196. The immune cell of claim 195, wherein the first antigen is a first tumor antigen and the second antigen is a second tumor antigen.

197. The immune cell of claim 196, wherein the first tumor antigen and the second tumor antigens are the same tumor antigen.

198. The immune cell of claim 196, wherein the first tumor antigen and the second tumor antigen are different tumor antigens.

199. The immune cell of a sample of the indications 195-198, in which the first tumor antigen and / or the second tumor antigen is MART-l / MelanA (MART-I), gplOO (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, GAGE-2, pl5, CEA, p53, Ras, HER-2 / neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus antigen EBVA, human papilomavirus (HPV) E6 or E7 antigen, TSP-180, MAGE-4, MAGE-5, MAGE-6, RAGE, NY-ESO, erbB, pl85erbB2, pl80erbB-3, c-met, nm-23Hl, PSA, TAG-72, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, beta-Catenin, CDK4, Mum-1, p 15, p 16, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, beta-HCG, BCA225, BTAA, CA 125, CA 15-3\CA 27.29\BCAA, CA 195, CA 242, CA-50, CAM43, CD68\P1, CO-029, FGF-5, G250, Ga733\EpCAM, HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB / 70K, NY-CO-1, RCAS1, SDCCAG16, TA-90\Mac-2-associated protein\cyclophilin C-associated protein, TAAL6, TAG72, TLP, MUC16, IL13Ro2, FRo, VEGFR2, Lewis Y, FAP, EphA2, CEACAM5, EGFR, CA6, CA9, GPNMB, EGP1, FOLR1, endothelial receptor, STEAP1, SLC44A4, Nectin-4, AGS-16, guanalil cyclase C, MUC-1, CFC1B, cadena alfa 3 de la integrina (de a3bl, una cadena receptora de laminin), TPS, CD19, CD20, CD22, CD30, CD72, CD180, CD171 (L1CAM), CD123, CD133, CD138, CD37, CD70, CD79a, CD79b, CD56, CD74, CD166, CD71, CLL-1 / CLEC12A, ROR1, Glipicano 3 (GPC3), Mesotelin, CD33 / IL3Ra, c-Met, PSCA, PSMA, Glucolípido F77, EGFRvIII, BCMA, GD-2, MY-ESO-1 o MAGE A3.

200. The immune cell of claim 198, wherein the first tumor antigen and the second tumor antigen are members of a pair selected from the group consisting of CD56 and CD138; CD56 and BCMA; CD138 and BCMA; IL-3R (CD123) and CD33; CD123 and CLEC12A; CD33 and CLEC12A; CD56 and c-KIT; CEA and PSMA; PSCA and PSMA; CEA and PSCA; CA-IX and CD70; HER2 and EGFR; EGFR and IGFR; MUC16 and Folate Receptor alpha; and Mesothelin and Folate Receptor alpha.

201. A method for treating a subject having a tumor, comprising administering to the subject the immune cell of any one of claims 190-200.