WO2022192286A1 - Compositions and methods for tcr reprogramming using fusion proteins and rna interference - Google Patents

Compositions and methods for tcr reprogramming using fusion proteins and rna interference Download PDF

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WO2022192286A1
WO2022192286A1 PCT/US2022/019385 US2022019385W WO2022192286A1 WO 2022192286 A1 WO2022192286 A1 WO 2022192286A1 US 2022019385 W US2022019385 W US 2022019385W WO 2022192286 A1 WO2022192286 A1 WO 2022192286A1
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seq
sequence
nucleic acid
acid sequence
sequence identity
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PCT/US2022/019385
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French (fr)
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Dario Gutierrez
Philippe KIEFFER-KWON
Julie DONAGHEY
Robert Hofmeister
Richard E. DECKER Jr.
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TCR2 Therapeutics Inc.
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Publication of WO2022192286A1 publication Critical patent/WO2022192286A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C07K14/7051—T-cell receptor (TcR)-CD3 complex
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2875—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K19/00—Hybrid peptides, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
    • C07K2317/569—Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®

Definitions

  • the pri-shRNAmiR comprises the miR scaffold comprising from 5' to 3': (a) the 5' pri-miR scaffold domain; (b) the 5' pri-miR basal stem domain; (c) the guide strand; (d) the pri-miR loop domain; (e) the passenger strand; (f) the 3' pri-miR basal stem domain; and (g) the 3' pri-miR scaffold domain.
  • the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the target sequence.
  • the target protein is B2M.
  • cell surface expression of B2M is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
  • the immune cell further comprises a sequence encoding a TCR beta constant domain.
  • the TCR beta constant domain is murine.
  • the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR beta.
  • the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR beta.
  • the constant domain of TCR beta is murine.
  • the immune cell further comprises a sequence encoding a TCR alpha constant domain.
  • n is an integer from 1 to 4.
  • at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit.
  • all three of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit.
  • the immune cell further comprises one or more sequences encoding a TCR constant domain selected from the group consisting of a TCR alpha constant domain, a TCR beta constant domain, a TCR gamma constant domain, and a TCR delta constant domain.
  • the immune cell further comprises: (a) a sequence encoding a TCR gamma constant domain and a TCR delta constant domain or (b) a sequence encoding a TCR alpha constant domain and a TCR beta constant domain.
  • the TCR alpha and TCR beta constant domains are murine.
  • the sequence encoding the TCR gamma constant domain further encodes a TCR gamma variable domain, thereby encoding a full TCR gamma domain.
  • the full TCR gamma domain is gamma 9 or gamma 4.
  • the antigen binding domain is selected from the group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, anti-MUC16 binding domain, an anti-Nectin-4 binding domain, an anti-GPC3 binding domain, and an anti-TROP-2 binding domain.
  • the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:60, a CDR2 of SEQ ID NO:61, and a CDR3 of SEQ ID NO:62.
  • the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:63, a CDR2 of SEQ ID NO:64, and a CDR3 of SEQ ID NO:65.
  • the anti-MSLN binding domain comprises a sequence with at least about 80% sequence identity to a sequence of SEQ ID NO:69, or SEQ ID NO:70.
  • the anti-CD19 binding domain comprises a light chain CDR1 of SEQ ID NO:73, a CDR2 of SEQ ID NO:75, and a CDR3 of SEQ ID NO:77.
  • the term “stimulatory molecule” or “stimulatory domain” refers to a molecule or portion thereof expressed by a T cell that provides the primary cytoplasmic signaling sequence(s) that regulate primary activation of the TCR complex in a stimulatory way for at least some aspect of the T cell signaling pathway.
  • the primary signal is initiated by, for instance, binding of a TCR/CD3 complex with an MHC molecule loaded with peptide, and which leads to mediation of a T cell response, including, but not limited to, proliferation, activation, differentiation, and the like.
  • the complex may be on the surface of an antigen presenting cell, such as a dendritic cell or a B cell, or any other cell, including cancer cells, or it may be immobilized by, for example, coating on to a bead or plate.
  • HLA human leukocyte antigen system
  • MHC major histocompatibility complex
  • HLA alleles A, B and C present peptides derived mainly from intracellular proteins, e.g., proteins expressed within the cell.
  • antibody fragments include, but are not limited to, Fab, Fab’, F(ab’)2, and Fv fragments, single-chain (sc)Fv (“scFv”) antibody fragments, linear antibodies, single domain antibodies such as sdAb (either V L or V H ), camelid V HH domains, and multi-specific antibodies formed from antibody fragments.
  • an antigen need not be encoded by a “gene” at all. It is readily apparent that an antigen can be generated synthesized or can be derived from a biological sample, or might be macromolecule besides a polypeptide.
  • a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a fluid with other biological components.
  • CD22 includes any of the recombinant or naturally- occurring forms of CD22 or variants or homologs thereof that have or maintain CD22 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity).
  • the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring BAFF.
  • BAFF is substantially identical to the protein identified by the UniProt reference number Q9Y275 or a variant or homolog having substantial identity thereto.
  • TRBC1 also known as TRBC1, BV05S1J2.2, TCRB, TCRBC1, T cell receptor beta constant 1, and T cell receptor beta constant 1, as referred herein, refers to a protein that in humans is encoded by the TRBC1 gene. TRBC1 contributes the beta chain to the larger TCR protein. TRBC1, as referred herein, includes any of the recombinant or naturally-occurring forms of TRBC1 or variants or homologs thereof that have or maintain TRBC1 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity).
  • encoding refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (e.g., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom.
  • a gene, cDNA, or RNA encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system.
  • nucleic acid or a peptide naturally present in a living animal is not “isolated,” but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is “isolated.”
  • An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell.
  • nucleic acid bases are used. “A” refers to adenosine, “C” refers to cytosine, “G” refers to guanosine, “T” refers to thymidine, and “U” refers to uridine.
  • Ranges throughout this disclosure, various aspects of the present disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6.
  • a range such as 95-99% identity includes something with 95%, 96%, 97%, 98% or 99% identity, and includes subranges such as 96-99%, 96-98%, 96-97%, 97-99%, 97-98% and 98-99% identity. This applies regardless of the breadth of the range.
  • the 3' pri-miR scaffold domain is about 49 nucleotides in length. In some of these embodiments, the 3' pri-miR scaffold domain is about 50 nucleotides in length. In particular embodiments, the 3' pri-miR scaffold domain has at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or more sequence identity to the sequence set forth as SEQ ID NO:164.
  • the guide strand is about 15 to about 25 nucleotides in length, including but not limited to about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, and about 25 nucleotides long. In some of these embodiments, the guide strand is about 22 nucleotides in length. In particular embodiments wherein the shRNA sequence from which the shRNAmiR is derived is less than 22 nucleotides in length, which is the length of most naturally-occurring microRNAs, an additional nucleotide is added to the shRNA sequence and in certain embodiments, this additional nucleotide is one that is complementary with the corresponding position within the target mRNA.
  • the B2M-targeted shRNA may comprise a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more sequence identity to the nucleic acid sequence set forth in SEQ ID NO:190.
  • the shRNA comprises the sequence set forth in SEQ ID NO:190.
  • the shRNA comprises the sequence set forth in SEQ ID NO:190.
  • the shRNAmiR molecule or the shRNA molecule may target any region of a TRAC mRNA.
  • Representative TRAC mRNA and protein sequences are known in the art.
  • a non- limiting example of a TRAC mRNA sequence is NCBI Acc. No. X02592.1 and a TRAC protein sequence is NCBI Acc. No. NP_ P01848.2.
  • the present disclosure encompasses recombinant nucleic acid constructs encoding TFPs, wherein the TFP comprises an antibody fragment that binds specifically to mesothelin, e.g., human mesothelin, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof.
  • TFP comprises an antibody fragment that binds specifically to mesothelin, e.g., human mesothelin, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof.
  • the antigen-binding domain comprises an anti-CD70 single chain Fv (scFv) or an antibody fragment thereof.
  • the anti-CD70 scFv or antibody fragment thereof can comprise a heavy chain complementary determining region 1 (CDRH1) having a sequence of SEQ ID NO:361, a CDRH2 having a sequence of SEQ ID NO:362, and a CDRH3 having a sequence of SEQ ID NOs: 363.
  • the antigen binding domain of the TFP is engineered by modifying one or more amino acids within one or both variable regions (e.g., V H and/or V L ), for example within one or more CDR regions and/or within one or more framework regions.
  • the TFP composition of the present disclosure comprises an antibody fragment.
  • that antibody fragment comprises a scFv.
  • the antibody or antibody fragment of the present disclosure may further be modified such that they vary in amino acid sequence (e.g., from wild-type), but not in desired activity.
  • the extracellular domain comprises a sequence encoding the extracellular domain of a TCR alpha chain, a TCR beta chain, a TCR delta chain, or a TCR gamma chain having a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more amino acids at the N- or C-terminus or at both the N- and C-terminus.
  • na ⁇ ve T cell activation can be said to be mediated by two distinct classes of cytoplasmic signaling sequences: those that initiate antigen-dependent primary activation through the TCR (primary intracellular signaling domains) and those that act in an antigen-independent manner to provide a secondary or costimulatory signal (secondary cytoplasmic domain, e.g., a costimulatory domain).
  • primary intracellular signaling domains that act in a stimulatory manner may contain signaling motifs which are known as immunoreceptor tyrosine- based activation motifs (ITAMs).
  • ITAMs immunoreceptor tyrosine- based activation motifs
  • the cells expressing a TFP and an RNAi agent as described herein can further comprise a second TFP, e.g., a second TFP that includes a different antigen binding domain, e.g., to the same target (e.g., MSLN) or a different target (e.g., CD70, CD19, or MUC16).
  • a second TFP e.g., a second TFP that includes a different antigen binding domain, e.g., to the same target (e.g., MSLN) or a different target (e.g., CD70, CD19, or MUC16).
  • the antigen binding domains of the different TFPs can be such that the antigen binding domains do not interact with one another.
  • the 5’ and 3’ UTRs can be the naturally occurring, endogenous 5’ and 3’ UTRs for the nucleic acid of interest.
  • UTR sequences that are not endogenous to the nucleic acid of interest can be added by incorporating the UTR sequences into the forward and reverse primers or by any other modifications of the template.
  • the use of UTR sequences that are not endogenous to the nucleic acid of interest can be useful for modifying the stability and/or translation efficiency of the RNA.
  • Poly(A) tails of RNAs can be further extended following in vitro transcription with the use of a poly(A) polymerase, such as E. coli polyA polymerase (E-PAP).
  • E-PAP E. coli polyA polymerase
  • increasing the length of a poly(A) tail from 100 nucleotides to between 300 and 400 nucleotides results in about a two-fold increase in the translation efficiency of the RNA.
  • the attachment of different chemical groups to the 3’ end can increase mRNA stability. Such attachment can contain modified/artificial nucleotides, aptamers and other compounds.
  • ATP analogs can be incorporated into the poly(A) tail using poly(A) polymerase. ATP analogs can further increase the stability of the RNA.
  • the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of positions 2-173 of SEQ ID NO:152.
  • the constant domain can comprise a sequence or fragment thereof of positions 22-173 of SEQ ID NO:152.
  • the constant domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of positions 2-173 of SEQ ID NO:152.
  • the constant domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of positions 2-173 of SEQ ID NO:152.
  • the TCR delta constant domain can comprise SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:243 or SEQ ID NO:265, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications.
  • the sequence encoding the TCR delta constant domain can further encode a TCR delta variable domain, thereby encoding a full TCR delta domain.
  • the TCR delta domain can be delta 2 or delta 1.
  • the full TCR delta domain can comprise SEQ ID NO:256, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0637]
  • the TCR constant domain incorporates into a functional TCR complex when expressed in a T cell.
  • the TCR subunit can comprise (i) at least a portion of a TCR extracellular domain, (ii) a TCR transmembrane domain, and (iii) a TCR intracellular domain of a TCR gamma chain or a TCR delta chain.
  • the TCR extracellular domain can comprise the extracellular portion of a constant domain of a TCR gamma chain or a TCR delta chain, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications.
  • the TCR constant domain is a TCR gamma constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR beta, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof;
  • the TCR constant domain is a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR gamma, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof;
  • the TCR constant domain is a TCR gamma constant domain and a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof;
  • the TCR constant domain is a TCR alpha constant domain and the TFP functionally integrates into a TCR complex
  • the present disclosure in some cases, provides a recombinant nucleic acid comprising (a) a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, (2) a transmembrane domain, and (3) an intracellular domain of TCR alpha, TCR beta, TCR gamma, or TCR delta or an intracellular domain comprising a stimulatory domain from an intracellular signaling domain of CD3 epsilon, CD3 gamma, or CD3 delta, and (ii) a binding ligand or a fragment thereof that is capable of binding to an antibody or fragment thereof; and (b) an RNAi agent or the sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, where-in the target protein is a protein associated with alloreactivity; wherein the TCR subunit and the binding lig
  • the present disclosure provides an exemplary recombinant nucleic acid that comprises any one transgene nucleic acid sequence listed in in Table 3 or 5.
  • Vectors [0691] The present disclosure provides a vector comprising the recombinant nucleic acid molecule encoding the TFP described herein.
  • the vector can comprise an RNAi agent or the sequence encoding the RNAi agent.
  • the vector can be directly transduced into a cell, e.g., a T cell.
  • the nucleic acid can be cloned into a number of types of vectors.
  • the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid.
  • Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors.
  • the expression vector may be provided to a cell in the form of a viral vector.
  • Such assays include, for example, “molecular biological” assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; “biochemical” assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and western blots) or by assays described herein to identify agents falling within the scope of the present disclosure.
  • Genetically-Modified Immune Cells [0707] The present disclosure provides genetically-modified immune cells and populations thereof and methods for producing the same.
  • the genetically-modified immune cells of the presently disclosed compositions and methods are human immune cells.
  • the immune cells are T cells, or cells derived therefrom.
  • the T cell is a CD8+ T cell, a CD4+ T cell, a na ⁇ ve T cell, a memory stem T cell, a central memory T cell, a double negative T cell, an effector memory T cell, an effector T cell, a ThO cell, a TcO cell, a Th1 cell, a Tc1 cell, a Th2 cell, a Tc2 cell, a Th17 cell, a Th22 cell, a gamma delta T cell, a natural killer (NK) cell, a natural killer T (NKT) cell, a hematopoietic stem cell, or a pluripotent stem cell.
  • the T cell is a CD8+ or CD4+ T cell.
  • the agent which inhibits an inhibitory molecule comprises a first polypeptide, e.g., an inhibitory molecule, associated with a second polypeptide that provides a positive signal to the cell, e.g., an intracellular signaling domain described herein.
  • a concentration of 2 billion cells/mL is used.
  • a concentration of 1 billion cells/mL is used.
  • greater than 100 million cells/mL is used.
  • a concentration of cells of 10, 15, 20, 25, 30, 35, 40, 45, or 50 million cells/mL is used.
  • a concentration of cells from 75, 80, 85, 90, 95, or 100 million cells/mL is used.
  • concentrations of 125 or 150 million cells/mL can be used.
  • T cells are activated by stimulation with an anti-CD3 antibody and an anti- CD28 antibody in combination with cytokines that bind the common gamma-chain (e.g., IL-2, IL-7, IL-12, IL-15, IL-21, and others).
  • T cells are activated by stimulation with an anti-CD3 antibody and an anti-CD28 antibody in combination with 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 100 U/mL of IL-2, IL-7, and/or IL-15.
  • the cells are activated for 24 hours.
  • the aforementioned culture is maintained for about seven days prior to subculture in soluble anti-CD3, and IL-2.
  • T cells that have been exposed to varied stimulation times may exhibit different characteristics.
  • typical blood or apheresed peripheral blood mononuclear cell products have a helper T cell population (TH, CD4+) that is greater than the cytotoxic or suppressor T cell population (TC, CD8+).
  • TH, CD4+ helper T cell population
  • TC cytotoxic or suppressor T cell population
  • Ex vivo expansion of T cells by stimulating CD3 and CD28 receptors produces a population of T cells that prior to about days 8-9 consists predominately of TH cells, while after about days 8-9, the population of T cells comprises an increasingly greater population of TC cells.
  • TFP+ T cell groups Animals are assessed for leukemia at 1-week intervals. Survival curves for the TFP+ T cell groups are compared using the log-rank test. [0742] Dose dependent TFP treatment response can be evaluated (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). For example, peripheral blood is obtained 35-70 days after establishing leukemia in mice injected on day 21 with TFP T cells, an equivalent number of mock-transduced T cells, or no T cells. Mice from each group are randomly bled for determination of peripheral blood CD19+ ALL blast counts and then killed on days 35 and 49. The remaining animals are evaluated on days 57 and 70.
  • Methods of Producing Modified immune e.g., T cells
  • the method comprising (a) disrupting an endogenous TCR gene encoding a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, or any combination thereof; thereby producing a T cell containing a functional disruption of an endogenous TCR gene; and (b) transducing the T cell containing a functional disruption of an endogenous TCR gene with the recombinant nucleic acid of the disclosure, or the vectors disclosed herein.

Abstract

Provided herein are immune cells comprising recombinant nucleic acids comprising a sequence encoding T cell receptor (TCR) fusion proteins (TFPs) and an RNA interference (RNAi) agent or a sequence encoding the RNAi agent, and methods of use thereof for the treatment of diseases, including cancer.

Description

COMPOSITIONS AND METHODS FOR TCR REPROGRAMMING USING FUSION PROTEINS AND RNA INTERFERENCE CROSS-REFERENCE [0001] This application claims the benefit of U.S. Provisional Patent Application No. 63/158,623, filed March 09, 2021, which is incorporated herein by reference in its entirety. BACKGROUND OF THE INVENTION [0002] Most patients with hematological malignancies or with late-stage solid tumors are incurable with standard therapy. In addition, traditional treatment options often have serious side effects. Numerous attempts have been made to engage a patient's immune system for rejecting cancerous cells, an approach collectively referred to as cancer immunotherapy. However, several obstacles make it rather difficult to achieve clinical effectiveness. Although hundreds of so- called tumor antigens have been identified, these are often derived from self and thus can direct the cancer immunotherapy against healthy tissue, or are poorly immunogenic. Furthermore, cancer cells use multiple mechanisms to render themselves invisible or hostile to the initiation and propagation of an immune attack by cancer immunotherapies. [0003] Recent developments using chimeric antigen receptor (CAR) modified autologous T cell therapy, which relies on redirecting genetically engineered T cells to a suitable cell-surface molecule on cancer cells, show promising results in harnessing the power of the immune system to treat B cell malignancies (see, e.g., Sadelain et al., Cancer Discovery 3:388-398 (2013)). The clinical results with CD19-specific CAR T cells (called CTL019) have shown complete remissions in patients suffering from chronic lymphocytic leukemia (CLL) as well as in childhood acute lymphoblastic leukemia (ALL) (see, e.g., Kalos et al., Sci Transl Med 3:95ra73 (2011), Porter et al., NEJM 365:725-733 (2011), Grupp et al., NEJM 368:1509-1518 (2013)). An alternative approach is the use of T cell receptor (TCR) alpha and beta chains selected for a tumor-associated peptide antigen for genetically engineering autologous T cells. These TCR chains will form complete TCR complexes and provide the T cells with a TCR for a second defined specificity. Encouraging results were obtained with engineered autologous T cells expressing NY-ESO-1-specific TCR alpha and beta chains in patients with synovial carcinoma. [0004] Besides the ability for genetically modified T cells expressing a CAR or a second TCR to recognize and destroy respective target cells in vitro/ex vivo, successful patient therapy with engineered T cells may require the T cells to be capable of strong activation, expansion, persistence over time, as well as to exhibit reduced allogenicity to avoid immune responses, such as Graft Versus Host Disease (GVHD), and modified T cell rejection. SUMMARY OF THE INVENTION [0005] There is a dire need to improve genetically engineered, allogeneic T cells for more efficient treatment of cancer patients. [0006] Provided herein are immune cells comprising a recombinant nucleic acid comprising: (a) a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, and (2) a TCR transmembrane domain, and (ii) an antigen binding domain; and (b) an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with immunoreactivity. [0007] Provided herein also are immune cells comprising a recombinant nucleic acid comprising: (a) a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, and (2) a TCR transmembrane domain, and (ii) an antigen binding domain; and (b) an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with alloreactivity. [0008] In some embodiments, the sequence encoding the TFP and the RNAi agent or the sequence encoding the RNAi agent are contained within a same nucleic acid molecule. [0009] In some embodiments, the sequence encoding the TFP and the RNAi agent or the sequence encoding the RNAi agent are contained within different nucleic acid molecules. [0010] In some embodiments, the RNAi agent is a short hairpin RNA (shRNA). [0011] In some embodiments, the RNAi agent is a microRNA (miRNA). [0012] In some embodiments, the RNAi agent is a pri-microRNA-adapted shRNA (pri- shRNAmiR), wherein the pri-shRNAmiR is processed in the immune cell to generate a microRNA-adapted shRNA (shRNAmiR) that reduces expression of the target protein in the immune cell. [0013] In some embodiments, the target protein is selected from the group consisting of beta-2 microglobulin (B2M), TRAC, TRBC1, TRBC2, CIITA, and CD70. [0014] In some embodiments, the immune cell is a T cell, an NKT cell, or an NK cell. [0015] In some embodiments, the T cell is an alpha beta (αβ) T cell. [0016] In some embodiments, the ab T cell is a CD4+ or CD8+ αβ T cell. [0017] In some embodiments, the T cell is a gamma delta (γδ) T cell. [0018] In some embodiments, the γδ T cell is a Vδ 1+ Vδ 2- γδ T cell. [0019] In some embodiments, the γδ T cell is a Vδ 1+ Vδ 2+ γδ T cell. [0020] In some embodiments, the γδ T cell is a Vδ 1- Vδ 2- γδ T cell. [0021] In some embodiments, the immune cell comprises an RNAi agent that reduces expression of a B2M protein, and any one selected from the group consisting of an RNAi agent that reduces expression of a TRAC protein, an RNAi agent that reduces expression of a TRBC1 protein, and an RNAi agent that reduces expression of a TRBC2 protein. [0022] In some embodiments, the TCR transmembrane domain is from CD3 gamma, CD3 delta, or CD3 epsilon, and wherein the immune cell further comprises one or more sequences encoding a TCR constant domain. [0023] In some embodiments, the TCR constant domain is selected from the group consisting of a TCR alpha constant domain and a TCR beta constant domain. [0024] In some embodiments, the TCR transmembrane domain is from TCR alpha or TCR beta. [0025] In some embodiments, the TCR transmembrane domain is from TCR gamma or TCR delta, and wherein the immune cell comprises an RNAi agent that reduces expression of a B2M protein. [0026] In some embodiments, the immune cell comprises a single RNAi agent that reduces expression of a B2M protein. [0027] In some embodiments, the TCR transmembrane domain is from CD3 gamma, CD3 delta, or CD3 epsilon. [0028] In some embodiments, the shRNAmiR comprises a guide strand and a passenger strand. [0029] In some embodiments, the G/C content of the shRNAmiR is between 30% and 50% or 36% and 45%. [0030] In some embodiments, the G/C content of the shRNAmiR is about 40%. [0031] In some embodiments, the pri-shRNAmiR comprises an miR scaffold of mouse origin or of human origin. [0032] In some embodiments, the pri-shRNAmiR comprises a miR scaffold comprising from 5' to 3': (a) a 5' pri-miR scaffold domain; (b) a 5' pri-miR basal stem domain; (c) a guide strand or a passenger strand; (d) a pri-miR loop domain; (e) a guide strand or a passenger strand; (f) a 3' pri- miR basal stem domain; and (g) a 3' pri-miR scaffold domain. [0033] In some embodiments, the pri-shRNAmiR comprises the miR scaffold comprising from 5' to 3': (a) the 5' pri-miR scaffold domain; (b) the 5' pri-miR basal stem domain; (c) the guide strand; (d) the pri-miR loop domain; (e) the passenger strand; (f) the 3' pri-miR basal stem domain; and (g) the 3' pri-miR scaffold domain. [0034] In some embodiments, the pri-shRNAmiR is processed by microprocessor to generate a pre-miR comprising: (a) the guide strand or the passenger strand; (b) the pre-miR loop domain; and (c) the guide strand or the passenger strand. [0035] In some embodiments, the pri-shRNAmiR is processed by microprocessor to generate the pre-miR comprising: (a) the guide strand; (b) the pre-miR loop domain; and (c) the passenger strand. [0036] In some embodiments, the pre-shRNAmiR is processed by dicer to generate the shRNAmiR. [0037] In some embodiments, the pri-shRNAmiR comprises a miR-30 scaffold, a miR-15 scaffold, a miR-16 scaffold, a miR-155 scaffold, an eSIBR scaffold, a miR-22 scaffold, a miR- 103 scaffold, a miR-107 scaffold, a miR- 196a2 scaffold sequence or a scaffold sequence from the miR-106a~363 cluster of mouse origin or human origin, or a variant thereof. [0038] In some embodiments, the miR-30 scaffold is a miR-30a scaffold. [0039] In some embodiments, the pri-shRNAmiR comprises the miR-155 scaffold. [0040] In some embodiments, the pri-shRNAmiR scaffold is based on murine miR-155 scaffold AY096003.1. [0041] In some embodiments, the pri-shRNAmiR comprises an enhanced synthetic inhibitory BIC/miR-155 RNA (eSIBR) scaffold. [0042] In some embodiments, the miR scaffold comprises a U at position -14 and a G at position -13 relative to a 5’ microprocessor cleavage site. [0043] In some embodiments, the miR scaffold comprises a CNNC motif beginning at positions +16 +17 +18 or +19 relative to a 3' microprocessor cleavage site. [0044] In some embodiments, (a) the 5' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:161; (c) the pri-miR loop domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:164. [0045] In some embodiments, (a) the 5' pri-miR scaffold domain comprises the nucleic acid sequence of SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises the nucleic acid sequence of SEQ ID NO:161; (c) the pri-miR loop domain comprises the nucleic acid sequence of SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises the nucleic acid sequence of SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises the nucleic acid sequence of SEQ ID NO:164. [0046] In some embodiments, the guide strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:284; the passenger strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:286, or a combination thereof. In some embodiments, the guide strand comprises the nucleic acid sequence of SEQ ID NO:284; the passenger strand comprises the nucleic acid sequence of SEQ ID NO:286, or a combination thereof. [0047] In some embodiments, the guide strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:284; the pre-miR loop domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:285; the passenger strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:286, or any combination thereof. [0048] In some embodiments, the guide strand comprises the nucleic acid sequence of SEQ ID NO:284; the pre-miR loop domain comprises the nucleic acid sequence of SEQ ID NO:285; the passenger strand comprises the nucleic acid sequence of SEQ ID NO:286, or any combination thereof. [0049] In some embodiments, the sequence encoding the pri-shRNAmiR is located within an intron. [0050] In some embodiments, the sequence encoding the pri-shRNAmiR is located within a promoter. [0051] In some embodiments, the sequence encoding the pri-shRNAmiR is located within an intron within a promoter. [0052] In some embodiments, the sequence encoding the pri-shRNAmiR is located within a 5’ UTR or a 3’ UTR. [0053] In some embodiments, the pri-shRNAmiR is at least about 50 nucleotides in length. [0054] In some embodiments, the pri-shRNAmiR is at most about 500 nucleotides in length. [0055] In some embodiments, the pri-shRNAmiR is from about 100 to about 300 nucleotides in length. [0056] In some embodiments, the pri-shRNAmiR is from about 120 to about 200 nucleotides in length. [0057] In some embodiments, the guide strand is 15-25 nucleotides in length. [0058] In some embodiments, the guide strand is 20-25 nucleotides in length. [0059] In some embodiments, the passenger strand is 15-25 nucleotides in length. [0060] In some embodiments, the passenger strand is 19-22 nucleotides in length. [0061] In some embodiments, the guide strand is longer than the passenger strand. [0062] In some embodiments, the guide strand is two nucleotides longer than the passenger strand. [0063] In some embodiments, the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the passenger sequence. [0064] In some embodiments, the guide strand comprises two mismatches with the passenger strand. [0065] In some embodiments, the guide strand comprises two mismatches with the passenger strand separated by three nucleotides. [0066] In some embodiments, the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the target sequence. [0067] In some embodiments, the target protein is B2M. [0068] In some embodiments, cell surface expression of B2M is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0069] In some embodiments, expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0070] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:165. [0071] In some embodiments, the passenger strand comprises a nucleic acid sequence of SEQ ID NO:166. [0072] In some embodiments, the passenger strand comprises a nucleic acid sequence of SEQ ID NO:286. [0073] In some embodiments, the guide strand comprises a nucleic acid sequence of SEQ ID NO:167. [0074] In some embodiments, the guide strand comprises a nucleic acid sequence of SEQ ID NO:284. [0075] In some embodiments, the shRNAmiR comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:168. [0076] In some embodiments, the shRNAmiR comprises a nucleic acid sequence of SEQ ID NO:168. [0077] In some embodiments, the immune cell comprises a functional disruption of an endogenous TCR. [0078] In some embodiments, the functional disruption of an endogenous TCR is a disruption of one or more of TRAC, TRBC1, or TRBC2. [0079] In some embodiments, the target protein is TRAC. [0080] In some embodiments, cell surface expression of TRAC is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0081] In some embodiments, guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:169. [0082] In some embodiments, the target protein is TRBC1. [0083] In some embodiments, cell surface expression of TRBC1 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0084] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:173. [0085] In some embodiments, the target protein is TRBC2. [0086] In some embodiments, cell surface expression of TRBC2 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0087] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:177. [0088] In some embodiments, the target protein is CIITA. [0089] In some embodiments, cell surface expression of CIITA is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0090] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:181. [0091] In some embodiments, the target protein is CD70. [0092] In some embodiments, cell surface expression of CD70 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0093] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:191. [0094] In some embodiments, the TCR subunit further comprises an intracellular domain. [0095] In some embodiments, the TFP functionally interacts with an endogenous TCR complex when expressed in a T cell. [0096] In some embodiments, the TCR intracellular domain comprises a stimulatory domain from an intracellular signaling domain of CD3 gamma, CD3 delta, or CD3 epsilon. [0097] In some embodiments, the TCR intracellular domain comprises an intracellular domain from TCR alpha, TCR beta, TCR gamma, or TCR delta. [0098] In some embodiments, the antigen binding domain is connected to the TCR extracellular domain by a linker sequence. [0099] In some embodiments, the linker is 120 amino acids in length or less. [0100] In some embodiments, the linker sequence comprises (G4S)n, wherein G is glycine, S is serine, and n is an integer from 1 to 10. [0101] In some embodiments, n is an integer from 1 to 4. [0102] In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit. [0103] In some embodiments, all three of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit. [0104] In some embodiments, the immune cell further comprises one or more sequences encoding a TCR constant domain selected from the group consisting of a TCR alpha constant domain, a TCR beta constant domain, a TCR gamma constant domain, and a TCR delta constant domain. [0105] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 epsilon. [0106] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 delta. [0107] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 gamma. [0108] In some embodiments, the immune cell further comprises: (a) a sequence encoding a TCR gamma constant domain and a TCR delta constant domain or (b) a sequence encoding a TCR alpha constant domain and a TCR beta constant domain. [0109] In some embodiments, the TCR alpha and TCR beta constant domains are murine. [0110] In some embodiments, the sequence encoding the TCR gamma constant domain further encodes a TCR gamma variable domain, thereby encoding a full TCR gamma domain. [0111] In some embodiments, the full TCR gamma domain is gamma 9 or gamma 4. [0112] In some embodiments, the sequence encoding the TCR delta constant domain further encodes a TCR delta variable domain, thereby encoding a full TCR delta domain. [0113] In some embodiments, the full TCR delta domain is delta 2 or delta 1. [0114] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR alpha. [0115] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR alpha. [0116] In some embodiments, the constant domain of TCR alpha is murine. [0117] In some embodiments, the immune cell further comprises a sequence encoding a TCR beta constant domain. [0118] In some embodiments, the TCR beta constant domain is murine. [0119] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR beta. [0120] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR beta. [0121] T In some embodiments, the constant domain of TCR beta is murine. [0122] In some embodiments, the immune cell further comprises a sequence encoding a TCR alpha constant domain. [0123] In some embodiments, the TCR alpha constant domain is murine. [0124] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR gamma. [0125] In some embodiments, the immune cell further comprises a sequence encoding a TCR delta constant domain. [0126] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR delta. [0127] In some embodiments, the immune cell further comprises a sequence encoding a TCR gamma constant domain. [0128] In some embodiments, the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain further encodes a second antigen binding domain that is operatively linked to the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain. [0129] In some embodiments, the second antigen binding domain is same as or different from the antigen binding domain or ligand binding domain of the TFP. [0130] In some embodiments, the recombinant nucleic acid molecule further comprises the one or more sequences encoding a TCR constant domain. [0131] In some embodiments, the encoded TFP and the encoded TCR constant domains are operatively linked by a second linker sequence. [0132] In some embodiments, the second linker comprises a protease cleavage site. [0133] In some embodiments, the protease cleavage site is a 2A cleavage site. [0134] In some embodiments, the 2A protease cleavage site is a T2A cleavage site or a P2A cleavage site. [0135] In some embodiments, the antigen binding domain is an antibody or a fragment thereof. [0136] In some embodiments, the antigen binding domain is a camelid antibody or a binding fragment thereof. [0137] In some embodiments, the antigen binding domain is a murine antibody or a binding fragment thereof. [0138] In some embodiments, the antigen binding domain is a human or humanized antibody or a binding fragment thereof. [0139] In some embodiments, the antigen binding domain is a single-chain variable fragment (scFv) or a single domain antibody (sdAb) domain. [0140] In some embodiments, the sdAb is a VHH. [0141] In some embodiments, the antigen binding domain is selected from the group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, anti-MUC16 binding domain, an anti-Nectin-4 binding domain, an anti-GPC3 binding domain, and an anti-TROP-2 binding domain. [0142] In some embodiments, the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:60, a CDR2 of SEQ ID NO:61, and a CDR3 of SEQ ID NO:62. [0143] In some embodiments, the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:63, a CDR2 of SEQ ID NO:64, and a CDR3 of SEQ ID NO:65. [0144] In some embodiments, the anti-MSLN binding domain comprises a sequence with at least about 80% sequence identity to a sequence of SEQ ID NO:69, or SEQ ID NO:70. [0145] In some embodiments, the anti-CD19 binding domain comprises a light chain CDR1 of SEQ ID NO:73, a CDR2 of SEQ ID NO:75, and a CDR3 of SEQ ID NO:77. [0146] In some embodiments, the anti-CD19 binding domain comprises a heavy chain CDR1 of SEQ ID NO:79, a CDR2 of SEQ ID NO:81, and a CDR3 of SEQ ID NO:83. [0147] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:88, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:90. [0148] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:92, a CDR2 of SEQ ID NO:93, and a CDR3 of SEQ ID NO:94. [0149] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:96, a CDR2 of SEQ ID NO:97, and a CDR3 of SEQ ID NO:98. [0150] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:100, a CDR2 of SEQ ID NO:101, and a CDR3 of SEQ ID NO:102. [0151] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:104, a CDR2 of SEQ ID NO:105, and a CDR3 of SEQ ID NO:106. [0152] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:108, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:110. [0153] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:112, a CDR2 of SEQ ID NO:113, and a CDR3 of SEQ ID NO:114. [0154] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:116, a CDR2 of SEQ ID NO:117, and a CDR3 of SEQ ID NO:118. [0155] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:120, a CDR2 of SEQ ID NO:121, and a CDR3 of SEQ ID NO:122. [0156] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:361, a CDR2 of SEQ ID NO:362, and a CDR3 of SEQ ID NO:363. [0157] In some embodiments, the anti-CD70 binding domain comprises a light chain CDR1 of SEQ ID NO:365, a CDR2 of SEQ ID NO:366, and a CDR3 of SEQ ID NO:367. [0158] In some embodiments, the anti-CD70 binding domain comprise a heavy chain variable (VH) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:364. [0159] In some embodiments, the anti-CD70 binding domain comprise a light chain variable (VL) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:368. [0160] In some embodiments, the cell is a T cell, and wherein the expressed TFP functionally incorporates into a TCR complex of the T cell. [0161] In some embodiments, the cell is a gamma delta (γδ) T cell, and wherein the expressed TFP functionally incorporates into a γδ TCR complex of the γδ T cell. [0162] In some embodiments, the RNAi agent or the sequence encoding the RNAi agent comprises the sequence of SEQ ID NO:185. [0163] In some embodiments, the RNAi agent or the sequence encoding the RNAi agent comprises the sequence of SEQ ID NO:186. [0164] In some embodiments, the RNAi agent or the sequence encoding the RNAi agent comprises the sequence of SEQ ID NO:187. [0165] In some embodiments, the RNAi agent or the sequence encoding the RNAi agent is operably linked to the sequence of SEQ ID NO:188. [0166] In some embodiments, the RNAi agent or the sequence encoding the RNAi agent is operably linked to the sequence of SEQ ID NO:189. [0167] In some embodiments, the recombinant nucleic acid comprises the sequence of SEQ ID NO:190. [0168] In some embodiments, a T cell expressing the TFP inhibits tumor growth when expressed in a T cell. [0169] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising: (i) a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (ii) a CSF2RA signal peptide, a CD19 binder light chain, a Whitlow linker, a CD19 binder heavy chain, an mmTRAC, a GSG-P2A sequence, a CSF2RA signal peptide, a CD19 binder light chain, a Whitlow linker, a CD19 binder heavy chain, an mmTRBC, or any combination thereof; (iii) a CSF2RA signal peptide, an mmTRAC, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (iv) a CSF2RA signal peptide, an MSLN binder, an mmTRAC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an mmTRBC, or any combination thereof; (v) a CSF2RA signal peptide, an mmTRAC PRT, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (vi) a CSF2RA signal peptide, an MSLN binder, an mmTRAC, a GSG- P2A sequence, a CSF2RA signal peptide, an MSLN binder, an mmTRBC, or any combination thereof; (vii) a CSF2RA signal peptide, an mmTRAC, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (viii) a CSF2RA signal peptide, a tEGFR, or any combination thereof; (ix) a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (x) a CSF2RA signal peptide, an MSLN binder, a TRDC, a furin cleavage sequence, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, a TRGC1, or any combination thereof; or (xi) a CSF2RA signal peptide, an MSLN binder, an A3(G4S) linker, a CD3e, or any combination thereof. [0170] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising, from N-terminal to C-terminal,: (i) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (ii) a CSF2RA signal peptide operatively linked to a CD19 binder light chain operatively linked to a Whitlow linker operatively linked to a CD19 binder heavy chain operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to a CD19 binder light chain operatively linked to a Whitlow linker operatively linked to a CD19 binder heavy chain operatively linked to an mmTRBC, or any combination thereof; (iii) a CSF2RA signal peptide operatively linked to an mmTRAC operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (iv) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRBC, or any combination thereof; (v) a CSF2RA signal peptide operatively linked to an mmTRAC PRT operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (vi) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRBC, or any combination thereof; (vii) a CSF2RA signal peptide operatively linked to an mmTRAC operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (viii) a CSF2RA signal peptide operatively linked to a tEGFR, or any combination thereof; (ix) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (x) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to a TRDC operatively linked to a furin cleavage sequence operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to a TRGC1, or any combination thereof; or (xi) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3(G4S) linker operatively linked to a CD3e or any combination thereof. [0171] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising: (i) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (ii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (iii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (iv) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (v) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (vi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (vii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (viii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:228, or any combination thereof; (ix) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (x) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:243, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:229, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:21, or any combination thereof; or (xi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof. [0172] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising, from N-terminal to C-terminal,: (i) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (ii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (iii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (iv) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (v) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (vi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (vii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (viii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:228, or any combination thereof; (ix) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (x) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:243 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:229 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:21, or any combination thereof; or (xi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof. [0173] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising: (i) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (ii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:85, the sequence of SEQ ID NO:227, the sequence of SEQ ID NO:87, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:85, the sequence of SEQ ID NO:227, the sequence of SEQ ID NO:87, the sequence of SEQ ID NO:209, or any combination thereof; (iii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (iv) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:209, or any combination thereof; (v) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (vi) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:209, or any combination thereof; (vii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (viii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:228, or any combination thereof; (ix) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (x) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:243, the sequence of SEQ ID NO:229, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:21, or any combination thereof; or (xi) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof. [0174] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising from N-terminal to C-terminal: (i) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (ii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:85 operatively linked to the sequence of SEQ ID NO:227 operatively linked to the sequence of SEQ ID NO:87 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:85 operatively linked to the sequence of SEQ ID NO:227 operatively linked to the sequence of SEQ ID NO:87 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (iii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (iv) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (v) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (vi) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (vii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (viii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:228, or any combination thereof; (ix) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (x) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:243 operatively linked to the sequence of SEQ ID NO:229 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:21, or any combination thereof; or (xi) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof. [0175] In some embodiments, the recombinant nucleic acid comprises: (i) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:282, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:283, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:289, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:291, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (ii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:293, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:294, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:295, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:296, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:297, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (iii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:299, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:300, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:301, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:302, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:303, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:304, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:307, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:308, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:309, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:310, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (iv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:312, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:283, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:313, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:314, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:316, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:319, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:321, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (v) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:324, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:325, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:326, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:327, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:328, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (vi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:336, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:337, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:338, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:339, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:340, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (vii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:344, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:345, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:346, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:347, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:348, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (viii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:350, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:351, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:352, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:353, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:354, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (ix) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:356, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:357, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:358, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:359, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:360, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (x) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:375, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:377, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:378, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:379, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:380, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:381, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:383, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xiii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:385, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:386, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xiv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:388, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:389, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:379, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:390, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:381, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:391, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:393, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:394, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xvi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:396, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:397, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xvii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:399, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:400, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xviii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:402, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:403, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:404, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xix) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:406, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:407, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:408, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xx) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:410, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:411, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:412, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:414, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:415, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:416, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:418, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:419, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:420, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:423, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:424, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxiii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:426, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:427, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:428, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:429, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:430, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxiv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:432, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:433, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:434, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:435, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:436, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:438, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:439, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:440, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:441, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:442, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxvi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:444, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:445, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:447, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:448, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxvii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:450, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:451, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:452, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:453, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxviii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:455, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:456, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:457, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; or (xxix) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:330, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:331, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:332, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:333, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:334, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof. [0176] In some embodiments, the recombinant nucleic acid comprises: (i) the sequence of SEQ ID NO:282, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:283, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:289, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:291, the sequence of SEQ ID NO:292, or any combination thereof; (ii) the sequence of SEQ ID NO:293, the sequence of SEQ ID NO:294, the sequence of SEQ ID NO:295, the sequence of SEQ ID NO:296, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:297, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:292, or any combination thereof; (iii) the sequence of SEQ ID NO:299, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:300, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:301, the sequence of SEQ ID NO:302, the sequence of SEQ ID NO:303, the sequence of SEQ ID NO:304, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:307, the sequence of SEQ ID NO:308, the sequence of SEQ ID NO:309, the sequence of SEQ ID NO:310, the sequence of SEQ ID NO:292, or any combination thereof; (iv) the sequence of SEQ ID NO:312, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:283, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:313, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:314, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:316, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:319, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:321, the sequence of SEQ ID NO:292, or any combination thereof; (v) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:324, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:325, the sequence of SEQ ID NO:326, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:327, the sequence of SEQ ID NO:328, the sequence of SEQ ID NO:292, or any combination thereof; (vi) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:336, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:337, the sequence of SEQ ID NO:338, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:339, the sequence of SEQ ID NO:340, the sequence of SEQ ID NO:292, or any combination thereof; (vii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:344, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:345, the sequence of SEQ ID NO:346, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:347, the sequence of SEQ ID NO:348, the sequence of SEQ ID NO:292, or any combination thereof; (viii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:350, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:351, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:352, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:353, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:354, the sequence of SEQ ID NO:292, or any combination thereof; (ix) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:356, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:357, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:358, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:359, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:360, the sequence of SEQ ID NO:292, or any combination thereof; (x) the sequence of SEQ ID NO:375, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:292, or any combination thereof; (xi) the sequence of SEQ ID NO:377, the sequence of SEQ ID NO:378, the sequence of SEQ ID NO:379, the sequence of SEQ ID NO:380, the sequence of SEQ ID NO:381, the sequence of SEQ ID NO:292, or any combination thereof; (xii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:383, the sequence of SEQ ID NO:292, or any combination thereof; (xiii) the sequence of SEQ ID NO:385, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:386, the sequence of SEQ ID NO:292, or any combination thereof; (xiv) the sequence of SEQ ID NO:388, the sequence of SEQ ID NO:389, the sequence of SEQ ID NO:379, the sequence of SEQ ID NO:390, the sequence of SEQ ID NO:381, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:391, the sequence of SEQ ID NO:292, or any combination thereof; (xv) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:393, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:394, the sequence of SEQ ID NO:292, or any combination thereof; (xvi) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:396, the sequence of SEQ ID NO:397, the sequence of SEQ ID NO:292, or any combination thereof; (xvii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:399, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:400, the sequence of SEQ ID NO:292, or any combination thereof; (xviii) the sequence of SEQ ID NO:402, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:403, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:404, the sequence of SEQ ID NO:292, or any combination thereof; (xix) the sequence of SEQ ID NO:406, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:407, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:408, the sequence of SEQ ID NO:292, or any combination thereof; (xx) the sequence of SEQ ID NO:410, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:411, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:412, the sequence of SEQ ID NO:292, or any combination thereof; (xxi) the sequence of SEQ ID NO:414, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:415, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:416, the sequence of SEQ ID NO:292, or any combination thereof; (xxii) the sequence of SEQ ID NO:418, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:419, the sequence of SEQ ID NO:420, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:423, the sequence of SEQ ID NO:424, the sequence of SEQ ID NO:292, or any combination thereof; (xxiii) the sequence of SEQ ID NO:426, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:427, the sequence of SEQ ID NO:428, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:429, the sequence of SEQ ID NO:430, the sequence of SEQ ID NO:292, or any combination thereof; (xxiv) the sequence of SEQ ID NO:432, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:433, the sequence of SEQ ID NO:434, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:435, the sequence of SEQ ID NO:436, the sequence of SEQ ID NO:292, or any combination thereof; (xxv) the sequence of SEQ ID NO:438, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:439, the sequence of SEQ ID NO:440, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:441, the sequence of SEQ ID NO:442, the sequence of SEQ ID NO:292, or any combination thereof; (xxvi) the sequence of SEQ ID NO:444, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:445, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:447, the sequence of SEQ ID NO:448, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292, or any combination thereof; (xxvii) the sequence of SEQ ID NO:450, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:451, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:452, the sequence of SEQ ID NO:453, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292; or (xxviii) the sequence of SEQ ID NO:455, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:456, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:457, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292, or any combination thereof; or (xxix) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:330, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:331, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:332, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:333, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:334, the sequence of SEQ ID NO:292, or any combination thereof. [0177] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence having at least 70% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264. [0178] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264. [0179] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:2- 15, 65-68, 71, 159, 192-194, 198, 199, and 221-224. [0180] In some embodiments, the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:2-15, 65-68, 71, 159, 192-194, 198, 199, and 221-224. [0181] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:230-241 and 269-281. [0182] In some embodiments, the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:230-241 and 269-281. [0183] In an aspect, the present disclosure provides a recombinant nucleic acid as described herein. [0184] In some embodiments, the recombinant nucleic acid as described herein further comprises a leader sequence. [0185] In some embodiments, the recombinant nucleic acid as described herein further comprises a promoter sequence. [0186] In some embodiments, the recombinant nucleic acid as described herein further comprises a sequence encoding a poly(A) tail. [0187] In some embodiments, the recombinant nucleic acid as described herein further comprises a 3’UTR sequence. [0188] In some embodiments, the recombinant nucleic acid as described herein comprises the sequence of SEQ ID NO:190. [0189] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence having at least 70% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264. [0190] In some embodiments, the recombinant nucleic acid encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264. [0191] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:2- 15, 65-68, 71, 159, 192-194, 198, 199, and 221-224. [0192] In some embodiments, the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:2-15, 65-68, 71, 159, 192-194, 198, 199, and 221-224. [0193] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:230-241 and 269-281. [0194] In some embodiments, the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:230-241 and 269-281. [0195] In an aspect, the present disclosure provides a vector comprising the recombinant nucleic acid as described herein. [0196] In some embodiments, the vector is selected from the group consisting of a DNA, an RNA, a plasmid, a lentivirus vector, adenoviral vector, an adeno-associated viral vector (AAV), a Rous sarcoma viral (RSV) vector, and a retrovirus vector. [0197] In some embodiments, the vector is an lentiviral vector. [0198] In some embodiments, the vector as described herein further comprises a promoter. [0199] In an aspect, the present disclosure provides a pharmaceutical composition comprising: (a) the immune cell as described herein; and (b) a pharmaceutically acceptable carrier. [0200] In an aspect, the present disclosure provides a method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition as described herein, wherein the administering is effective to treat cancer in the subject. [0201] In some embodiments, less cytokines are released in the subject compared to a subject administered an effective amount of an immune cell not comprising the pri-shRNAmiR. [0202] In some embodiments, the cancer is a solid cancer, a lymphoma or a leukemia. [0203] In some embodiments, the cancer is selected from the group consisting of renal cell carcinoma, breast cancer, lung cancer, ovarian cancer, prostate cancer, colon cancer, cervical cancer, brain cancer, liver cancer, pancreatic cancer, kidney cancer, and stomach cancer. [0204] In some embodiments, less cytokines are released in the subject compared to a subject administered an effective amount of an autologous T cell expressing the TFP as described herein and not expressing the shRNAmiR. [0205] In some embodiments, the method does not induce graft versus host disease. [0206] In some embodiments, the subject has a reduced risk of developing graft versus host disease compared to a subject administered an effective amount of an autologous T cell expressing the TFP as described herein, and not expressing the shRNAmiR. [0207] In an aspect, the present disclosure provides an engineered RNAi agent comprising a pri- microRNA-adapted shRNA (pri-shRNAmiR) or a sequence encoding the pri-shRNAmiR, wherein the pri-shRNAmiR is processed in an immune cell to generate a microRNA-adapted shRNA (shRNAmiR) that reduces expression of a target protein in the immune cell; and wherein the target protein is selected from the group consisting of B2M, TRAC, TRBC1, TRBC2, CIITA, and CD70. [0208] In some embodiments, the shRNAmiR comprises a guide strand and a passenger strand. [0209] In some embodiments, the G/C content of the shRNAmiR is between 30% and 50% or 36% and 45%. [0210] In some embodiments, the G/C content of the shRNAmiR is about 40%. [0211] In some embodiments, the pri-shRNAmiR comprises an miR scaffold of mouse origin or human origin. [0212] In some embodiments, the pri-shRNAmiR comprises a miR scaffold comprising from 5' to 3': (a) a 5' pri-miR scaffold domain; (b) a 5' pri-miR basal stem domain; (c) a guide strand or a passenger strand; (d) a pri-miR loop domain; (e) a guide strand or a passenger strand; (f) a 3' pri- miR basal stem domain; and (g) a 3' pri-miR scaffold domain. [0213] In some embodiments, the pri-shRNAmiR comprises the miR scaffold comprising from 5' to 3': (a) the 5' pri-miR scaffold domain; (b) the 5' pri-miR basal stem domain; (c) the guide strand; (d) the pri-miR loop domain; (e) the passenger strand; (f) the 3' pri-miR basal stem domain; and (g) the 3' pri-miR scaffold domain. [0214] In some embodiments, the pri-shRNAmiR is processed by microprocessor to generate a pre-miR comprising: (a) the guide strand or the passenger strand; (b) the pre-miR loop domain; and (b) the guide strand or the passenger strand. [0215] In some embodiments, the pri-shRNAmiR is processed by microprocessor to generate the pre-miR comprising: (a) the guide strand; (b) the pre-miR loop domain; and (c) the passenger strand. [0216] In some embodiments, the pre-shRNAmiR is processed by dicer to generate the shRNAmiR. [0217] In some embodiments, the pri-shRNAmiR comprises a miR-30 scaffold, a miR-15 scaffold, a miR-16 scaffold, a miR-155 scaffold, an eSIBR scaffold, a miR-22 scaffold, a miR- 103 scaffold, a miR-107 scaffold, a miR- 196a2 scaffold sequence or a scaffold sequence from the miR-106a~363 cluster of mouse origin or human origin, or a variant thereof. [0218] In some embodiments, the miR-30 scaffold is a miR-30a scaffold. [0219] In some embodiments, the pri-shRNAmiR comprises the miR-155 scaffold. [0220] In some embodiments, the pri-shRNAmiR scaffold is based on murine miR-155 scaffold AY096003.1. [0221] In some embodiments, the pri-shRNAmiR comprises an enhanced synthetic inhibitory BIC/miR-155 RNA (eSIBR) scaffold. [0222] In some embodiments, the miR scaffold comprises a U at position -14 and a G at position -13 relative to a 5’ microprocessor cleavage site. [0223] In some embodiments, the miR scaffold comprises a CNNC motif beginning at positions +16 +17 +18 or +19 relative to a 3' microprocessor cleavage site. [0224] In some embodiments, (a) the 5' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:161; (c) the pri-miR loop domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:164. [0225] In some embodiments, (a) the 5' pri-miR scaffold domain comprises a nucleic acid sequence of SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises a nucleic acid sequence of SEQ ID NO:161; (c) the pri-miR loop domain comprises a nucleic acid sequence of SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises a nucleic acid sequence of SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises a nucleic acid sequence of SEQ ID NO:164. [0226] In some embodiments, the sequence encoding the pri-shRNAmiR is located within an intron. [0227] In some embodiments, the sequence encoding the pri-shRNAmiR is located within a promoter. [0228] In some embodiments, the sequence encoding the shRNAmiR is located within an intron within a promoter. [0229] In some embodiments, the sequence encoding the pri-shRNAmiR is located within a 5’ UTR or a 3’ UTR. [0230] In some embodiments, the pri-shRNAmiR is at least about 50 nucleotides in length. [0231] In some embodiments, the pri-shRNAmiR is at most about 500 nucleotides in length. [0232] In some embodiments, the pri-shRNAmiR is from about 100 to about 300 nucleotides in length. [0233] In some embodiments, the pri-shRNAmiR is from about 120 to about 200 nucleotides in length. [0234] In some embodiments, the guide strand is 15-25 nucleotides in length. [0235] In some embodiments, the guide strand is 20-25 nucleotides in length. [0236] In some embodiments, the passenger strand is 15-25 nucleotides in length. [0237] In some embodiments, the passenger strand is 19-22 nucleotides in length. [0238] In some embodiments, the guide strand is longer than the passenger strand. [0239] In some embodiments, the guide strand is two nucleotides longer than the passenger strand. [0240] In some embodiments, the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the passenger sequence. [0241] In some embodiments, the guide strand comprises two mismatches with the passenger strand. [0242] In some embodiments, the guide strand comprises two mismatches with the passenger strand separated by three nucleotides. [0243] In some embodiments, the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the target sequence. [0244] In some embodiments, the target protein is B2M. [0245] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:165. [0246] In some embodiments, the passenger strand comprises a nucleic acid sequence of SEQ ID NO:166. [0247] In some embodiments, the guide strand comprises a nucleic acid sequence of SEQ ID NO:167. [0248] In some embodiments, the shRNAmiR comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:168. [0249] In some embodiments, the shRNAmiR comprises a nucleic acid sequence of SEQ ID NO:168. [0250] In some embodiments, the target protein is TRAC. [0251] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:169. [0252] In some embodiments, the target protein is TRBC1. [0253] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:173. [0254] In some embodiments, the target protein is TRBC2. [0255] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:177. [0256] In some embodiments, the target protein is CIITA. [0257] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:181. [0258] In some embodiments, the target protein is CD70. [0259] In some embodiments, cell surface expression of CD70 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell. [0260] In some embodiments, the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:191. [0261] In some embodiments, the engineered RNAi agent comprises the sequence of SEQ ID NO:185. [0262] In some embodiments, the engineered RNAi agent comprises the sequence of SEQ ID NO:186. [0263] In some embodiments, the engineered RNAi agent comprises the sequence of SEQ ID NO:187. [0264] In some embodiments, the engineered RNAi agent is operably linked to the sequence of SEQ ID NO:188. [0265] In some embodiments, the engineered RNAi agent is operably linked to the sequence of SEQ ID NO:189. [0266] In an aspect, the present disclosure provides a composition comprising the engineered RNAi agent as described herein, and a recombinant nucleic acid sequence encoding a T-cell receptor fusion protein (TFP) or the TFP, wherein the TFP comprises: (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, and (2) a TCR transmembrane domain, and (ii) an antigen binding domain. [0267] In some embodiments, the TCR subunit further comprises an intracellular domain. [0268] In some embodiments, the TFP functionally interacts with an endogenous TCR complex when expressed in a T cell. [0269] In some embodiments, the TCR intracellular domain comprises a stimulatory domain from an intracellular signaling domain of CD3 gamma, CD3 delta, or CD3 epsilon. [0270] In some embodiments, the TCR intracellular domain comprises an intracellular domain from TCR alpha, TCR beta, TCR gamma, or TCR delta. [0271] In some embodiments, the antigen binding domain is connected to the TCR extracellular domain by a linker sequence. [0272] In some embodiments, the linker is 120 amino acids in length or less. [0273] In some embodiments, the linker sequence comprises (G4S)n, wherein G is glycine, S is serine, and n is an integer from 1 to 10. [0274] In some embodiments, n is an integer from 1 to 4. [0275] In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit. [0276] In some embodiments, all three of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit. [0277] In some embodiments, the immune cell further comprises one or more sequences encoding a TCR constant domain selected from the group consisting of a TCR alpha constant domain, a TCR beta constant domain, a TCR gamma constant domain, and a TCR delta constant domain. [0278] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 epsilon. [0279] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 delta. [0280] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 gamma. [0281] In some embodiments, the immune cell further comprises: (a) a sequence encoding a TCR gamma constant domain and a TCR delta constant domain or (b) a sequence encoding a TCR alpha constant domain and a TCR beta constant domain. [0282] In some embodiments, the TCR alpha and TCR beta constant domains are murine. [0283] In some embodiments, the sequence encoding the TCR gamma constant domain further encodes a TCR gamma variable domain, thereby encoding a full TCR gamma domain. [0284] In some embodiments, the full TCR gamma domain is gamma 9 or gamma 4. [0285] In some embodiments, wherein the sequence encoding the TCR delta constant domain further encodes a TCR delta variable domain, thereby encoding a full TCR delta domain. [0286] In some embodiments, the full TCR delta domain is delta 2 or delta 1. [0287] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR alpha. [0288] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR alpha. [0289] In some embodiments, the constant domain of TCR alpha is murine. [0290] In some embodiments, the immune cell further comprises a sequence encoding a TCR beta constant domain. [0291] In some embodiments, the TCR beta constant domain is murine. [0292] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR beta. [0293] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR beta. [0294] In some embodiments, the constant domain of TCR beta is murine. [0295] In some embodiments, the immune cell further comprises a sequence encoding a TCR alpha constant domain. [0296] In some embodiments, the TCR alpha constant domain is murine. [0297] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR gamma. [0298] In some embodiments, the immune cell further comprises a sequence encoding a TCR delta constant domain. [0299] In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR delta.\ [0300] In some embodiments, the immune cell further comprises a sequence encoding a TCR gamma constant domain. [0301] In some embodiments, the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain further encodes a second antigen binding domain that is operatively linked to the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain. [0302] In some embodiments, the second antigen binding domain is same as or different from the antigen binding domain or ligand binding domain of the TFP. [0303] In some embodiments, the recombinant nucleic acid molecule further comprises the one or more sequences encoding a TCR constant domain. [0304] In some embodiments, the encoded TFP and the encoded TCR constant domains are operatively linked by a second linker sequence. [0305] In some embodiments, the second linker comprises a protease cleavage site. [0306] In some embodiments, the protease cleavage site is a 2A cleavage site. [0307] In some embodiments, the 2A protease cleavage site is a T2A cleavage site or a P2A cleavage site. [0308] In some embodiments, the antigen binding domain is an antibody or a fragment thereof. [0309] In some embodiments, the antigen binding domain is a camelid antibody or a binding fragment thereof. [0310] In some embodiments, the antigen binding domain is a murine antibody or a binding fragment thereof. [0311] In some embodiments, the antigen binding domain is a human or humanized antibody or a binding fragment thereof. [0312] In some embodiments, the antigen binding domain is a single-chain variable fragment (scFv) or a single domain antibody (sdAb) domain. [0313] In some embodiments, the sdAb is a VHH. [0314] In some embodiments, the antigen binding domain is selected from the group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, anti-MUC16 binding domain, an anti-Nectin-4 binding domain, an anti-GPC3 binding domain, and an anti-TROP-2 binding domain. [0315] In some embodiments, the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:60, a CDR2 of SEQ ID NO:61, and a CDR3 of SEQ ID NO:62. [0316] In some embodiments, the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:63, a CDR2 of SEQ ID NO:64, and a CDR3 of SEQ ID NO:65. [0317] In some embodiments, the anti-MSLN binding domain comprises a sequence with at least about 80% sequence identity to a sequence of SEQ ID NO:69, or SEQ ID NO:70. [0318] In some embodiments, the anti-CD19 binding domain comprises a light chain CDR1 of SEQ ID NO:73, a CDR2 of SEQ ID NO:75, and a CDR3 of SEQ ID NO:77. [0319] In some embodiments, the anti-CD19 binding domain comprises a heavy chain CDR1 of SEQ ID NO:79, a CDR2 of SEQ ID NO:81, and a CDR3 of SEQ ID NO:83. [0320] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:88, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:90. [0321] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:92, a CDR2 of SEQ ID NO:93, and a CDR3 of SEQ ID NO:94. [0322] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:96, a CDR2 of SEQ ID NO:97, and a CDR3 of SEQ ID NO:98. [0323] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:100, a CDR2 of SEQ ID NO:101, and a CDR3 of SEQ ID NO:102. [0324] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:104, a CDR2 of SEQ ID NO:105, and a CDR3 of SEQ ID NO:106. [0325] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:108, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:110. [0326] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:112, a CDR2 of SEQ ID NO:113, and a CDR3 of SEQ ID NO:114. [0327] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:116, a CDR2 of SEQ ID NO:117, and a CDR3 of SEQ ID NO:118. [0328] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:120, a CDR2 of SEQ ID NO:121, and a CDR3 of SEQ ID NO:122. [0329] In some embodiments, the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:361, a CDR2 of SEQ ID NO:362, and a CDR3 of SEQ ID NO:363. [0330] In some embodiments, the anti-CD70 binding domain comprises a light chain CDR1 of SEQ ID NO:365, a CDR2 of SEQ ID NO:366, and a CDR3 of SEQ ID NO:367. [0331] In some embodiments, the anti-CD70 binding domain comprise a heavy chain variable (VH) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:364. [0332] In some embodiments, the anti-CD70 binding domain comprise a light chain variable (VL) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:368. [0333] In some embodiments, the cell is a T cell, and wherein the expressed TFP functionally incorporates into a TCR complex of the T cell. [0334] In some embodiments, the cell is a gamma delta (γδ) T cell, and wherein the expressed TFP functionally incorporates into a γδ TCR complex of the γδ T cell. [0335] In some embodiments, a T cell expressing the TFP inhibits tumor growth when expressed in a T cell. [0336] In some embodiments, the composition comprises a recombinant nucleic acid having the sequence of SEQ ID NO:190. [0337] In another aspect, the present disclosure provides a method of producing the immune cell as provided herein, the method comprising: (a) delivering into the immune cell an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with immunoreactivity; and (b) transducing a sequence encoding a TFP as provided herein. [0338] In another aspect, the present disclosure provides a method of producing the immune cell as provided herein, the method comprising: (a) delivering into the immune cell an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with alloreactivity; and (b) transducing a sequence encoding a TFP as provided herein. [0339] In some embodiments, the target protein is selected from the group consisting of beta-2 microglobulin (B2M), TRAC, TRBC1, TRBC2, CIITA, and CD70. [0340] In some embodiments, the TFP comprises: (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, and (2) a transmembrane domain, and (ii) an antibody domain comprising an antigen binding domain. [0341] In some embodiments, the sequence encoding the TFP further encodes a TCR constant domain. [0342] In some embodiments, the sequence encoding the TCR constant domain further encodes a second antigen binding domain that is operatively linked to the sequence encoding the TCR constant domain INCORPORATION BY REFERENCE [0343] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. BRIEF DESCRIPTION OF THE DRAWINGS [0344] FIGs.1A and 1B are diagrams showing an exemplary expression cassettes containing a B2M shRNAor pri-shRNAmiR under the control of U6 promoter. [0345] FIGs.2A-2B are a series of flow cytometry graphs showing evaluation of transduction efficiency, B2M expression, and MHC1 expression in T cells. The horizontal axis denotes trEGFR, B2M, or MHC1 expression, as indicated, and the vertical axis denotes side scatter area (SSC-A). The graphs show flow cytometry analysis of live cells. FIG.2A shows B2M and MHC1 levels trEGFR+ cells and FIG.2B shows B2M and MHC1 levels in trEGFR- cells. [0346] FIGs.3A-3C are a series of flow cytometry graphs showing transduction efficiency, B2M expression, and HLA-A2 expression in untransduced T cells, T cells transduced with TC- 210, or T cells transduced with MH1-CD3e and expressing the B2M mirtron. The graphs show flow cytometry analysis of live cells. FIG.3A shows transduction efficiency. FIG.3B shows B2M and HLA-A2 expression in TFP+ cells. FIG.3C shows B2M and HA-A2 expression in TFP- cells. [0347] FIG.4 is a schematic showing an assessment of B2M mirtron TRuCs (TFPs) in Jurkat TRAC knock-out (KO) cells. On day 0, Jurkat TRAC KO cells were thawed. On day 1, Jurkat TRAC KO cells were transduced with vectors containing FMC63-αC P2A FMC63-βC with or without the B2M mirtron and 1:1000 LentiBOOST. On day 4, Jurkat TRAC KO cells were expanded. On day 7, TRuC% and B2M were assessed. [0348] FIG.5 is a series of graphs showing transduction efficiency and B2M expression of cells prepared according to the methods shown in FIG.4. Flow cytometry data is shown illustrating transduction efficiency is shown in wt nontransduced cells, wt cells transduced with TC-110, or TRA-/- cells transduced with FMC63-αC P2A FMC63-βC with or without the B2M mirtron. B2M levels in transduced cells are shown. [0349] FIG.6 is a schematic showing an assessment of B2M mirtron-expressing TRuCs in T- cells (e.g., R021 T-cells). On day 0, T cells from donor R021 were thawed and activated. On day 1, T cells were transduced with TFP vectors and 1:1000 LentiBOOST. On day 4, T cells were edited to knock out TRAC and expanded. On day 7, transduction efficiency, B2M, and HLA-A2 levels were assessed. [0350] FIG.7 is a series of flow cytometry graphs showing transduction efficiency and B2M expression in nontransduced cells, wt donor T cells transduced with TC-210, and TRA-/- donor T cells transduced with MH1-αC P2A MH1-βC with or without the B2M mirtron. B2M expression is shown in transduced (TFP+) cells. [0351] FIGs.8A-8E are a series of flow cytometry graphs showing transduction efficiency, B2M expression, and HLA-A2 expression in TRA-/- donor T cells transduced with MH1-αC P2A MH1-βC with or without the B2M mirtron and in control cells (non-transduced wild-type, TRA-/-, and TRA-/-, B2M-/-). Transduction efficiency is shown in FIG.8A. B2M expression is shown in TFP+ cells in FIG.8B and in TFP- cells in FIG.8C. HLA-A2 expression is shown in TFP+ cells in FIG.8D and in TFP- cells in FIG.8E. [0352] FIG.9 is a series of graphs showing cytotoxicity of untransduced, TC-210, or TRA-/- donor T cells transduced with MH1-αC P2A MH1-βC with or without the B2M mirtron when cocultured with MSLN positive (MSTO-mlsn-luc) or MLSN negative (C30-luc) target cell lines at an E:T ratio of 9:1, 3:1, or 1:1. DETAILED DESCRIPTION OF THE INVENTION [0353] Disclosed herein, in some embodiments, is an immune cell comprising a recombinant nucleic acid comprising: a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising a TCR subunit comprising (i) at least a portion of a TCR extracellular domain, and a TCR transmembrane domain, and (ii) an antigen binding domain. The immune cell can further comprise an RNA interference (RNAi) agent or a sequence encoding the RNAi agent. The RNAi agent can reduce expression of a target protein in the immune cell. The target protein can be a protein associated with alloreactivity. Also disclosed herein is a recombinant nucleic acid molecule or a vector comprising the recombinant nucleic acid molecule encoding the TFP. Also disclosed herein is a pharmaceutical compression comprising the immune cell described herein and a pharmaceutically acceptable carrier and methods of treating cancer in a subject by administering the pharmaceutical composition into the subject. [0354] In various embodiments, the engineered RNAi agent can comprise a pri-microRNA- adapted shRNA (pri-shRNAmiR) or a sequence encoding the pri-shRNAmiR. The pri- shRNAmiR can be processed in an immune cell to generate a microRNA-adapted shRNA (shRNAmiR) that reduces expression of a target protein in the immune cell. In other embodiments, the engineered RNAi agent can be an shRNA. The target protein can be selected from the group consisting of B2M, TRAC, TRBC1, TRBC2, CIITA, CD70, HLA-A, HLA-B, HLA-C, MICA, MICB, ULBP, PRV (PRV1; CD177), NKp30, NKp44, NKp46, HLA-DP, HLA- DQ, HLA-DR, TCRa (TCRα), TCRb (TCRβ), CD3e (CD3ε), CD3γ, CD3d (CD3δ), CD3z (CD3ζ), TET2, TET1, PD1, TIGIT, TIM3, LAG3, CTLA4, CD39, VISTA, NRA1, NRA2, NRA3, TOX1, TOX2, DGK, FAS, EOMES, PTPN2, PP2A, TGFBR1, TGFBR2, DNMT3A, and DNMT3B. DEFINITION [0355] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the invention pertains. [0356] The term “a” and “an” refers to one or to more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one element or more than one element. [0357] As used herein, “about” can mean plus or minus less than 1 or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, or greater than 30 percent, depending upon the situation and known or knowable by one skilled in the art. [0358] As used herein the specification, “subject” or “subjects” or “individuals” may include, but are not limited to, mammals such as humans or non-human mammals, e.g., domesticated, agricultural or wild, animals, as well as birds, and aquatic animals. “Patients” are subjects suffering from or at risk of developing a disease, disorder or condition or otherwise in need of the compositions and methods provided herein. [0359] As used herein, “treating” or “treatment” refers to any indicia of success in the treatment or amelioration of the disease or condition. Treating can include, for example, reducing, delaying or alleviating the severity of one or more symptoms of the disease or condition, or it can include reducing the frequency with which symptoms of a disease, defect, disorder, or adverse condition, and the like, are experienced by a patient. As used herein, “treat or prevent” is sometimes used herein to refer to a method that results in some level of treatment or amelioration of the disease or condition, and contemplates a range of results directed to that end, including but not restricted to prevention of the condition entirely. [0360] As used herein, “preventing” refers to the prevention of the disease or condition, e.g., tumor formation, in the patient. For example, if an individual at risk of developing a tumor or other form of cancer is treated with the methods of the present disclosure and does not later develop the tumor or other form of cancer, then the disease has been prevented, at least over a period of time, in that individual. [0361] As used herein, a “therapeutically effective amount” is the amount of a composition or an active component thereof sufficient to provide a beneficial effect or to otherwise reduce a detrimental non-beneficial event to the individual to whom the composition is administered. By “therapeutically effective dose” herein is meant a dose that produces one or more desired or desirable (e.g., beneficial) effects for which it is administered, such administration occurring one or more times over a given period of time. The exact dose will depend on the purpose of the treatment, and will be ascertainable by one skilled in the art using known techniques (see, e.g. Lieberman, Pharmaceutical Dosage Forms (vols.1-3, 1992); Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); and Pickar, Dosage Calculations (1999)). [0362] As used herein, the term “RNA interference (RNAi),” also known as co-suppression, post-transcriptional gene silencing (PTGS), and quelling, refers to a biological process in which RNA molecules inhibit gene expression or translation by neutralizing targeted mRNA molecules. [0363] As used herein, the term “RNAi agent” refers to an agent that induces or promotes RNA interference. In some embodiments, an RNAi agent induces or promotes RNA interference in vivo, in vitro, in cells, in tissues or in subjects. In some embodiments, an RNAi agent is an RNA, a DNA, a nucleotide, a nucleic acid, a oligonucleotide or a polynucleotide. In some embodiments, an RNAi agent comprises a naturally occuring sequence. In some embodiments, an RNAi agent comprises an artificially generated sequence. In some embodiments, an RNAi agent is a small molecule. In some embodiments, an RNAi agent is a polypeptide. [0364] As used herein, the term “shRNA” or“ short hairpin RNA” refers to an artificial RNA molecule comprising a hairpin that can be used to silence gene expression vian RNA interference. [0365] As used herein, the term “miRNA” or “microRNA” or “miR” refers to mature microRNAs (miRNAs) that are endogenously encoded approximately 22 lit long RNAs that post- transcriptionally reduce the expression of target genes. miRNAs are found in plants, animals, and some viruses and are generally expressed in a highly tissue- or developmental- stage-specific fashion. [0366] As is used herein, the term “shRNAmiR” refers to the artificial RNA molecule that results after processing of the pri-shRNAmiR by Drosha to generate a pre-shRNAmiR comprising a guide strand, a passenger strand, and the pri-shRNAmiR stem loop, followed by cleavage of the pre-shRNAmiR by Dicer to remove the pri-shRNAmiR stem loop. In some embodiments, the shRNAmiR comprises a guide strand and a passenger strand. [0367] A "stem-loop structure" refers to a nucleic acid having a secondary structure that includes a region of nucleotides which are known or predicted to form a double strand (stem portion) that is linked on one side by a region of predominantly single- stranded nucleotides (loop portion), In some cases, the loop may also be very short and thereby not be recognized by Dicer, leading to Dicer-independent shRNAs (comparable to the endogenous miR0431). The term “hairpin” is also used herein to refer to stem-loop structures. The actual primary' sequence of nucleotides within the stern-loop structure is not critical to the practice of the description as long as the secondary structure is present. As is known in the art, the secondary structure does not require exact base-pairing. Thus, the stem may include one or more base mismatches. Alternatively, the base-pairing may be exact (i.e., not include any mismatches). [0368] As used herein, the terms “pri-shRNAmiR” and “pri-microRNA-adapted shRNA” refer to shRNA sequences embedded within a microRNA scaffold. A pri-shRNAmiR molecule mimics naturally-occurring pri-miRNA molecules in that they comprise a hairpin flanked by sequences necessary for efficient processing and can be processed by the Drosha enzyme (generating pre-shRNAmiRs), exported into the cytoplasm, and cleaved by Dicer, after which the mature shRNAmiR can enter the RISC. The microRNA scaffold can be derived from naturally- occurring microRNA, pre- miRNAs, or pri-miRNAs or variants thereof. In some embodiments, the shRNA sequences which the pri-shRNAmiR is based upon is of a different length from miRNAs (which are 22 nucleotides long) and the miRNA scaffold must therefore be modified in order to accommodate the longer or shorter shRNA sequence length. [0369] As used herein, the terms “microRNA flanking sequences” or “shRNAmiR flanking sequences” are used interchangeably and refer to nucleotide sequences comprising microRNA processing elements. MicroRNA processing elements are the minimal nucleic acid sequences which contribute to the production of mature microRNA from primary microRNA or precursor microRNA. Often these elements are located within a 40 nucleotide sequence that flanks a microRNA stem-loop structure. In some instances, the microRNA processing elements are found within a stretch of nucleotide sequences of between 5 and 4,000 nucleotides in length that flank a microRNA stem-loop structure. MicroRNA flanking sequences used in the pri-shRNAmiR molecules can be naturally-occurring sequences flanking naturally- occurring microRNA or can be variants thereof. MicroRNA flanking sequences include pri-miR scaffold domains and pri- miR basal stem domains. [0370] Pri-shRNAmiR molecules used in the presently disclosed compositions and methods can comprise in the 5' to 3' direction: (a) a 5' pri-miR scaffold domain; (b) a 5' pri-miR basal stem domain; (c) a passenger strand or a guide strand; (d) a pri-miR loop domain; (e) a passenger or a guide strand; (f) a 3' pri-miR basal stem domain; and (g) a 3' pri-miR scaffold domain. [0371] As used herein, the terms “pri-miR scaffold domain” and “miR scaffold domain” are used interchangeably as they relate to a pri-shRNAmiR, and refer to a nucleotide sequence that can flank either the 5' or 3' end of a shRNAmiR molecule and can be derived from a naturally- occurring microRNA flanking sequence or a variant thereof. In general, the pri-miR basal stem domain sequence separates the pre-shRNAmiR sequence (passenger and guide strand, and pri- miR loop domain) and the scaffold domains. The 5' pri-miR scaffold domain can comprise a restriction enzyme (e.g., type IIS restriction enzyme) recognition sequence at or near its 3' end and the 3' pri-miR scaffold domain can comprise a restriction enzyme recognition sequence at or near its 5' end, thus facilitating the insertion of a shRNAmiR sequence. In some embodiments, the secondary structure of the miR scaffold domain is more important than the actual sequence thereof. [0372] As used herein, the terms “miR basal stem domain” and “pri miR basal stem domain” are used interchangeably as they relate to a pri-shRNAmiR and refers to sequences immediately flanking the passenger and guide strand sequences that comprise the base of the hairpin stem below the passenger-guide duplex. Thus, the 5' and 3' pri-miR basal stem domains are complementary (fully or partially) in sequence to one another. In some embodiments, the 5' and 3' pri-miR basal stem domains comprise sequences that when hybridized together, form one or more mismatch bubbles, each comprising one or two mismatched base pairs. [0373] As used herein, the term “passenger strand” as it relates to a shRNAmiR or pri- shRNAmiR refers to the sequence of the shRNAmiR, which is complementary (fully or partially) to the guide sequence. [0374] As used herein, the term “guide strand” as it relates to a shRNAmiR or pri-shRNAmiR refers to the sequence of the shRNAmiR that has complementarity (full or partial) with the target mRNA sequence for which a reduction in expression is desired. [0375] As used herein, a “miR loop domain” or “pri-miR loop domain” as it relates to a pri- shRNAmiR refers to the single- stranded loop sequence at one end of the passengenger- guide duplex of the pri-shRNAmiR. The pri-miR loop domain can be derived from a naturally- occurring pre-microRNA loop sequence or a variant thereof. [0376] As used herein, the terms “cleave” or “cleavage” refer to the hydrolysis of phosphodiester bonds within the backbone of a recognition sequence within a target sequence that results in a double-stranded break within the target sequence, referred to herein as a “cleavage site”. [0377] As used herein, the term “reduced expression” in reference to a target protein (i.e., an endogenously expressed protein) refers to any reduction in the expression of the endogenous protein by a genetically-modified cell when compared to a control cell. The term reduced can also refer to a reduction in the percentage of cells in a population of cells that express wild-type levels of an endogenous protein targeted by a shRNAmiR of the disclosure when compared to a population of control cells. Such a reduction in the percentage of cells in a population that fully express the targeted endogenous protein may be up to 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or up to 100%. It is understood in the context of this disclosure that the term “reduced” encompasses a partial or incomplete knockdown of a target or endogenous protein, and is distinguished from a complete knockdown, such as that achieved by gene inactivation by a nuclease. [0378] As used herein, a “T cell receptor (TCR) fusion protein” or “TFP” includes a recombinant polypeptide derived from the various polypeptides comprising the TCR that is generally capable of i) binding to a surface antigen on target cells and ii) interacting with other polypeptide components of the intact TCR complex, typically when co-located in or on the surface of a T cell. [0379] The term “stimulation” refers to a primary response induced by binding of a stimulatory domain or stimulatory molecule (e.g., a TCR/CD3 complex) with its cognate ligand thereby mediating a signal transduction event, such as, but not limited to, signal transduction via the TCR/CD3 complex. Stimulation can mediate altered expression of certain molecules, and/or reorganization of cytoskeletal structures, and the like. [0380] The term “stimulatory molecule” or “stimulatory domain” refers to a molecule or portion thereof expressed by a T cell that provides the primary cytoplasmic signaling sequence(s) that regulate primary activation of the TCR complex in a stimulatory way for at least some aspect of the T cell signaling pathway. In one aspect, the primary signal is initiated by, for instance, binding of a TCR/CD3 complex with an MHC molecule loaded with peptide, and which leads to mediation of a T cell response, including, but not limited to, proliferation, activation, differentiation, and the like. A primary cytoplasmic signaling sequence (also referred to as a “primary signaling domain”) that acts in a stimulatory manner may contain a signaling motif which is known as immunoreceptor tyrosine-based activation motif or “ITAM”. Examples of an ITAM containing primary cytoplasmic signaling sequence that is of particular use in the invention includes, but is not limited to, those derived from TCR zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, CD278 (also known as “ICOS”) and CD66d. [0381] The term “antigen presenting cell” or “APC” refers to an immune system cell such as an accessory cell (e.g., a B-cell, a dendritic cell, and the like) that displays a foreign antigen complexed with major histocompatibility complexes (MHC’s) on its surface. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells. [0382] “Major histocompatability complex (MHC) molecules are typically bound by TCRs as part of peptide:MHC complex. The MHC molecule may be an MHC class I or II molecule. The complex may be on the surface of an antigen presenting cell, such as a dendritic cell or a B cell, or any other cell, including cancer cells, or it may be immobilized by, for example, coating on to a bead or plate. [0383] The “human leukocyte antigen system (HLA),” as used herein, refers to the gene complex which encodes major histocompatibility complex (MHC) in humans, and includes HLA class I antigens (A, B & C) and HLA class II antigens (DP, DQ, & DR). HLA alleles A, B and C present peptides derived mainly from intracellular proteins, e.g., proteins expressed within the cell. [0384] During T cell development in vivo, T cells undergo a positive selection step to ensure recognition of self MHCs followed by a negative step to remove T cells that bind too strongly to MHC which present self-antigens. As a consequence, certain T cells and the TCRs they express will only recognize peptides presented by certain types of MHC molecules - i.e., those encoded by particular HLA alleles. This is known as HLA restriction. [0385] In some embodiments, one HLA allele of interest is HLA-A*0201, which is expressed in the vast majority (>50%) of the Caucasian population. Accordingly, TCRs which bind WT1 peptides presented by MHC encoded by HLA-A*0201 (i.e. are HLA-A*0201 restricted) are advantageous since an immunotherapy making use of such TCRs will be suitable for treating a large proportion of the Caucasian population. [0386] In some embodiment, other HLA- A alleles of interest are HLA-A*0101, HLA-A*2402, and HLA-A*0301. [0387] In some embodiments, widely expressed HLA-B alleles of interest are HLA-B*3501, HLA-B*0702 and HLA-B*3502. [0388] The term “intracellular signaling domain,” as used herein, refers to an intracellular portion of a molecule. The intracellular signaling domain generates a signal that promotes an immune effector function of the TFP containing cell, e.g., a modified T-T cell. Examples of immune effector function, e.g., in a modified T-T cell, include, but are not limited to, cytolytic activity and T helper cell activity, including the secretion of cytokines. In some embodiments, the intracellular signaling domain comprises a primary intracellular signaling domain. Exemplary primary intracellular signaling domains include, but are not limited to, those derived from the molecules responsible for primary stimulation, or antigen dependent simulation. In some embodiments, the intracellular signaling domain comprises a costimulatory intracellular domain. Exemplary costimulatory intracellular signaling domains include, but are not limited to, those derived from molecules responsible for costimulatory signals, or antigen independent stimulation. [0389] In some embodiment, a primary intracellular signaling domain comprises an ITAM (“immunoreceptor tyrosine-based activation motif”). Examples of ITAM containing primary cytoplasmic signaling sequences include, but are not limited to, those derived from CD3 zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d DAP10 and DAP12. [0390] The term “costimulatory molecule,” as used herein, refers to the cognate binding partner on a T cell that specifically binds with a costimulatory ligand, thereby mediating a costimulatory response by the T cell, such as, but not limited to, proliferation. In some embodiments, costimulatory molecules are cell surface molecules other than antigen receptors or their ligands that are required for an efficient immune response. Exemplary costimulatory molecules include, but are not limited to, an MHC class 1 molecule, BTLA and a Toll ligand receptor, as well as OX40, CD2, CD27, CD28, CDS, ICAM-1, LFA-1 (CD11a/CD18) and 4-1BB (CD137). In some embodiments, a costimulatory intracellular signaling domain is the intracellular portion of a costimulatory molecule. In some embodiments, a costimulatory molecule is represented in the following protein families: TNF receptor proteins, Immunoglobulin-like proteins, cytokine receptors, integrins, signaling lymphocytic activation molecules (SLAM proteins), and activating NK cell receptors. Examples of such molecules include CD27, CD28, 4-1BB (CD137), OX40, GITR, CD30, CD40, ICOS, BAFFR, HVEM, lymphocyte function-associated antigen-1 (LFA- 1), CD2, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, and a ligand that specifically binds with CD83, and the like. In some embodiments, the intracellular signaling domain comprises the entire intracellular portion or the entire native intracellular signaling domain of the molecule from which it is derived, or a functional fragment thereof. [0391] The term “4-1BB,” as used herein, refers to a member of the TNFR superfamily with an amino acid sequence provided as GenBank Acc. No. AAA62478.2, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like; and a “4-1BB costimulatory domain,” as used herein, refers to amino acid residues 214-255 of GenBank Acc. No. AAA62478.2, or the equivalent residues from a non-human species, e.g., mouse, rodent, monkey, ape and the like. [0392] The term “antibody,” as used herein, refers to a protein, or polypeptide sequences derived from an immunoglobulin molecule, which specifically binds to an antigen. Antibodies can be intact immunoglobulins of polyclonal or monoclonal origin, or fragments thereof and can be derived from natural or from recombinant sources. [0393] The terms “antibody fragment” refers to at least one portion of an antibody, or recombinant variants thereof, that contains the antigen binding domain, i.e., an antigenic determining variable region of an intact antibody, that is sufficient to confer recognition and specific binding of the antibody fragment to a target, such as an antigen and its defined epitope. Examples of antibody fragments include, but are not limited to, Fab, Fab’, F(ab’)2, and Fv fragments, single-chain (sc)Fv (“scFv”) antibody fragments, linear antibodies, single domain antibodies such as sdAb (either VL or VH), camelid VHH domains, and multi-specific antibodies formed from antibody fragments. [0394] The term “scFv,” as used herein, refers to a fusion protein comprising at least one antibody fragment comprising a variable region of a light chain and at least one antibody fragment comprising a variable region of a heavy chain, wherein the light and heavy chain variable regions are contiguously linked via a short flexible polypeptide linker, and capable of being expressed as a single polypeptide chain, and wherein the scFv retains the specificity of the intact antibody from which it is derived. [0395] The term “Heavy chain variable region” or “ VH” with regard to an antibody, as used herein, refers to the fragment of the heavy chain that contains three CDRs interposed between flanking stretches known as framework regions. These framework regions are generally more highly conserved than the CDRs and form a scaffold to support the CDRs. A camelid “VHH” domain, as used herein, refers to a heavy chain comprising a single variable antibody domain. [0396] Unless specified, as used herein, a scFv may have the VL and VH variable regions in either order, e.g., with respect to the N-terminal and C-terminal ends of the polypeptide. In some embodiments, the scFv may comprise VL-linker-VH or may comprise VH-linker-VL. [0397] In some embodiments, the portion of the TFP composition of the disclosure comprising an antibody or antibody fragment thereof may exist in a variety of forms where the antigen binding domain is expressed as part of a contiguous polypeptide chain including, for example, a single domain antibody fragment (sdAb), or a single chain antibody (scFv) derived from a murine, humanized or human antibody (Harlow et al., 1999, In: Using Antibodies: A Laboratory Manual, Cold Spring Harbor Laboratory Press, N.Y.; Harlow et al., 1989, In: Antibodies: A Laboratory Manual, Cold Spring Harbor, N.Y.; Houston et al., 1988, Proc. Natl. Acad. Sci. USA 85:5879-5883; Bird et al., 1988, Science 242:423-426). In one aspect, the antigen binding domain of a TFP composition of the disclosure comprises an antibody fragment. In a further aspect, the TFP comprises an antibody fragment that comprises a scFv or a sdAb. [0398] The term “recombinant antibody,” as used herein, refers to an antibody that is generated using recombinant DNA technology, such as, for example, an antibody expressed by a bacteriophage or yeast expression system. The term should also be construed to mean an antibody which has been generated by the synthesis of a DNA molecule encoding the antibody and which DNA molecule expresses an antibody protein, or an amino acid sequence specifying the antibody, wherein the DNA or amino acid sequence has been obtained using recombinant DNA or amino acid sequence technology which is available and well known in the art. [0399] The term “antigen” or “Ag,” as used herein, refers to a molecule that is capable of being bound specifically by an antibody, or otherwise provokes an immune response. In some embodiments, this immune response may involve either antibody production, or the activation of specific immunologically-competent cells, or both. [0400] The skilled artisan will understand that any macromolecule, including virtually all proteins or peptides, can serve as an antigen. Furthermore, antigens can be derived from recombinant or genomic DNA. A skilled artisan will understand that any DNA, which comprises a nucleotide sequences or a partial nucleotide sequence encoding a protein that elicits an immune response therefore encodes an “antigen” as that term is used herein. Furthermore, one skilled in the art will understand that an antigen need not be encoded solely by a full length nucleotide sequence of a gene. It is readily apparent that the present disclosure includes, but is not limited to, the use of partial nucleotide sequences of more than one gene and that these nucleotide sequences are arranged in various combinations to encode polypeptides that elicit the desired immune response. Moreover, a skilled artisan will understand that an antigen need not be encoded by a “gene” at all. It is readily apparent that an antigen can be generated synthesized or can be derived from a biological sample, or might be macromolecule besides a polypeptide. Such a biological sample can include, but is not limited to a tissue sample, a tumor sample, a cell or a fluid with other biological components. [0401] As used herein, the term “CD19,” also known as B-lymphocyte antigen CD19, B4, CVID3, and CD19 molecule, refers to the Cluster of Differentiation 19 protein, which is an antigenic determinant detectable on B cell leukemia precursor cells, other malignant B cells and most cells of the normal B cell lineage. CD19, as referred herein, includes any of the recombinant or naturally-occurring forms of CD19 or variants or homologs thereof that have or maintain CD19 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring CD19. In some embodiments, CD19 is substantially identical to the protein identified by the UniProt reference number P15391 or a variant or homolog having substantial identity thereto. [0402] As used herein, the term “BCMA” refers to the B-cell maturation antigen, also known as tumor necrosis factor receptor superfamily member 17 (TNFRSF17), Cluster of Differentiation 269 protein (CD269), BCM, TNFRSF13A, tumor necrosis factor receptor superfamily member 17, and TNF receptor superfamily member 17, which is a protein that in humans is encoded by the TNFRSF17 gene. TNFRSF17 is a cell surface receptor of the TNF receptor superfamily which recognizes B-cell activating factor (BAFF) (see, e.g., Laabi et al., EMBO 11 (11): 3897– 904 (1992). This receptor is expressed in mature B lymphocytes, and may be important for B- cell development and autoimmune response. BCMA, as referred herein, includes any of the recombinant or naturally-occurring forms of BCMA or variants or homologs thereof that have or maintain BCMA activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring BCMA. In some embodiments, BCMA is substantially identical to the protein identified by the UniProt reference number Q02223 or a variant or homolog having substantial identity thereto. [0403] As used herein, the term “CD16,” also known as FcγRIII, refers to a cluster of differentiation molecule found on the surface of natural killer cells, neutrophil polymorphonuclear leukocytes, monocytes, and macrophages. CD16 has been identified as Fc receptors FcγRIIIa (CD16a) and FcγRIIIb (CD16b), which participate in signal transduction. In some embodiments, CD16 is a molecule of the immunoglobulin superfamily (IgSF) involved in antibody-dependent cellular cytotoxicity (ADCC). CD16, as referred herein, includes any of the recombinant or naturally-occurring forms of CD16 or variants or homologs thereof that have or maintain CD16 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring CD16. In some embodiments, CD16 is substantially identical to the protein identified by the UniProt reference number P08637 (CD16a) or a variant or homolog having substantial identity thereto or the protein identified by the UniProt reference number O7501 (CD16b) or a variant or homolog having substantial identity thereto. [0404] As used herein, the term “NKG2D,” also known as KLRK1, CD314, D12S2489E, KLR, NKG2-D, NKG2D, natural killer group 2D, killer cell lectin-like receptor K1, and killer cell lectin like receptor K1, refers to a transmembrane protein belonging to the CD94/NKG2 family of C-type lectin-like receptors. In some embodiments, in humans, NKG2D is expressed by NK cells, γδ T cells and CD8+ αβ T cells. In some embodiments, NKG2D recognizes induced-self proteins from MIC and RAET1/ULBP families which appear on the surface of stressed, malignant transformed, and infected cells. NKG2D, as referred herein, includes any of the recombinant or naturally-occurring forms of NKG2D or variants or homologs thereof that have or maintain NKG2D activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring NKG2D. In some embodiments, NKG2D is substantially identical to the protein identified by the UniProt reference number P26718 or a variant or homolog having substantial identity thereto. [0405] The term “mesothelin (MSLN),” also known as MPF and SMRP, refers to a tumor differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. In some embodiments, mesothelin is over-expressed in several human tumors, including mesothelioma and ovarian and pancreatic adenocarcinoma. MSLN, as referred herein, includes any of the recombinant or naturally-occurring forms of MSLN or variants or homologs thereof that have or maintain MSLN activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring MSLN. In some embodiments, MSLN is substantially identical to the protein identified by the UniProt reference number Q13421 or a variant or homolog having substantial identity thereto. [0406] The term “tyrosine-protein kinase transmembrane receptor ROR1”, also known as ROR1, neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), dJ537F10.1, receptor tyrosine kinase-like orphan receptor 1, and receptor tyrosine kinase like orphan receptor 1, refers to a member of the receptor tyrosine kinase-like orphan receptor (ROR) family. It plays a role in metastasis of cancer. ROR1, as referred herein, includes any of the recombinant or naturally- occurring forms of ROR1 or variants or homologs thereof that have or maintain ROR1 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring ROR1. In some embodiments, ROR1 is substantially identical to the protein identified by the UniProt reference number Q01973 or a variant or homolog having substantial identity thereto. [0407] The term “MUC16”, also known as mucin 16, cell-surface associated, ovarian cancer- related tumor marker CA125, CA-125 (cancer antigen 125, carcinoma antigen 125, or carbohydrate antigen 125), mucin 16, and CA125, refers to a membrane-tethered mucin that contains an extracellular domain at its amino terminus, a large tandem repeat domain, and a transmembrane domain with a short cytoplasmic domain. In some embodiments, products of this gene have been used as a marker for different cancers, with higher expression levels associated with poorer outcomes. MUC16, as referred herein, includes any of the recombinant or naturally-occurring forms of MUC16 or variants or homologs thereof that have or maintain MUC16 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring MUC16. In some embodiments, MUC16 is substantially identical to the protein identified by the UniProt reference number Q8WXI7 or a variant or homolog having substantial identity thereto. [0408] The term “CD22,” also known as cluster of differentiation-22, sialic acid binding Ig-like lectin 2, SIGLEC-2, SIGLEC2, CD22 molecule, T cell surface antigen leu-14, and B cell receptor CD22, refers to a protein that mediates B cell/B cell interactions, and is thought to be involved in, e.g., the localization of B cells in lymphoid tissues. In some embodiments, CD22 is associated with diseases including, but not limited to, refractory hematologic cancer and hairy cell leukemia. An exemplary fully human anti-CD22 monoclonal antibody (“M971”) suitable for use with the methods as described herein is described, e.g., in Xiao et al., MAbs.2009 May- Jun; 1(3): 297–303. CD22, as referred herein, includes any of the recombinant or naturally- occurring forms of CD22 or variants or homologs thereof that have or maintain CD22 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring CD22. In some embodiments, CD22 is substantially identical to the protein identified by the UniProt reference number P20273 or a variant or homolog having substantial identity thereto. [0409] “Programmed cell death protein 1,” also known as PD-1, CD279 (cluster of differentiation 279), PDCD1, PD1, SLEB2, hPD-1, hSLE1, and Programmed cell death 1, refers to a protein on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self- tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells. PD-1 is an immune checkpoint and guards against autoimmunity, e.g., through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells). PD-1 is a cell surface receptor that belongs to the immunoglobulin superfamily and is expressed on T cells and pro-B cells. PD-1 binds two ligands, PD-L1 and PD-L2. PD-1, as referred herein, includes any of the recombinant or naturally-occurring forms of PD-1 or variants or homologs thereof that have or maintain PD-1 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring PD-1. In some embodiments, PD-1 is substantially identical to the protein identified by the UniProt reference number Q15116 or a variant or homolog having substantial identity thereto. [0410] “Programmed death-ligand 1 (PD-L1),” also known as cluster of differentiation 274, CD274, B7 homolog 1, B7-H, B7-H1, B7H1, PDCD1L1, PDCD1LG1, PDL1, hPD-L1, and CD274 molecule, refers to a 40kDa type 1 transmembrane protein. In some embodiments, PD-L1 may play a major role in suppressing the adaptive arm of immune system during particular events such as, e.g., pregnancy, tissue allografts, autoimmune disease and other disease states such as, e.g., hepatitis. Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or endogenous danger signals. In turn, clonal expansion of antigen-specific CD8+ T cells and/or CD4+ helper cells is propagated. The binding of PD-L1 to the inhibitory checkpoint molecule PD-1 transmits an inhibitory signal based on interaction with phosphatases (SHP-1 or SHP-2) via Immunoreceptor Tyrosine-Based Switch Motif (ITSM) motif. This reduces the proliferation of antigen-specific T-cells in lymph nodes, while simultaneously reducing apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells) - further mediated by a lower regulation of the gene Bcl-2. PD-L1, as referred herein, includes any of the recombinant or naturally-occurring forms of PD-L1 or variants or homologs thereof that have or maintain PD-L1 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring PD-L1. In some embodiments, PD-L1 is substantially identical to the protein identified by the UniProt reference number Q9NZQ7 or a variant or homolog having substantial identity thereto. [0411] The “CD79α (Cluster of Differentiation 79α)” and “CD79β (Cluster of Differentiation 79β)” genes encode proteins that make up the B lymphocyte antigen receptor, a multimeric complex that includes the antigen-specific component, surface immunoglobulin (Ig). Surface Ig non-covalently associates with two other proteins, Ig-alpha and Ig-beta (encoded by CD79α and its paralog CD79β, respectively) which are necessary for expression and function of the B-cell antigen receptor. Functional disruption of this complex can lead to, e.g., human B-cell chronic lymphocytic leukemias. CD79α protein, as referred herein, includes any of the recombinant or naturally-occurring forms of CD79α protein or variants or homologs thereof that have or maintain CD79α protein activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring CD79α protein. In some embodiments, CD79α protein is substantially identical to the protein identified by the UniProt reference number P11912 or a variant or homolog having substantial identity thereto. CD79β protein, as referred herein, includes any of the recombinant or naturally- occurring forms of CD79β protein or variants or homologs thereof that have or maintain CD79β protein activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring CD79β protein. In some embodiments, CD79β protein is substantially identical to the protein identified by the UniProt reference number P40259 or a variant or homolog having substantial identity thereto. [0412] “B cell activating factor” or “BAFF,” also known as tumor necrosis factor ligand superfamily member 13B, TNFSF13B, BLYS, CD257, DTL, TALL-1, TALL1, THANK, TNFSF20, ZTNF4, TNLG7A, tumor necrosis factor superfamily member 13b, and TNF superfamily member 13b, refers to a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. This cytokine is a ligand for receptors TNFRSF13B/TACI, TNFRSF17/BCMA, and TNFRSF13C/BAFF-R. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. In some embodiments, BAFF plays an important role in the proliferation and differentiation of B cells. BAFF, as referred herein, includes any of the recombinant or naturally-occurring forms of BAFF or variants or homologs thereof that have or maintain BAFF activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring BAFF. In some embodiments, BAFF is substantially identical to the protein identified by the UniProt reference number Q9Y275 or a variant or homolog having substantial identity thereto. [0413] “Beta-2 microglobulin,” also known as β2 microglobulin, B2M, entrez:567, IMD43, beta-2-microglobulin, and Β2 microglobulin, as referred herein, refers to a component of major histocompatibility complex (MHC) class I molecules, which are one of two primary classes of MHC molecules (the other being MHC class II) and are found on the cell surface of nucleated cells. The function of MHC class I molecules is to display peptide fragments of proteins from within the cell to cytotoxic T cells, which in turn triggers an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein. In humans, the β2 microglobulin protein is encoded by the B2M gene. B2M, as referred herein, includes any of the recombinant or naturally-occurring forms of B2M or variants or homologs thereof that have or maintain B2M activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring B2M. In some embodiments, B2M is substantially identical to the protein identified by the UniProt reference number P61769 or a variant or homolog having substantial identity thereto. [0414] “TRAC,” also known as TRA, IMD7, TCRA, TRA@, TRAC, T-cell receptor alpha locus, TCRD, and T cell receptor alpha locus, as referred herein, refers to a protein that in humans is encoded by the TRA gene, also known as TCRA or TRA@. TRAC contributes the alpha chain to the larger T-cell receptor (TCR) protein. TRAC, as referred herein, includes any of the recombinant or naturally-occurring forms of TRAC or variants or homologs thereof that have or maintain TRAC activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring TRAC. In some embodiments, TRAC is substantially identical to the protein identified by the UniProt reference number P01848 or a variant or homolog having substantial identity thereto. [0415] “TRBC1,” also known as TRBC1, BV05S1J2.2, TCRB, TCRBC1, T cell receptor beta constant 1, and T cell receptor beta constant 1, as referred herein, refers to a protein that in humans is encoded by the TRBC1 gene. TRBC1 contributes the beta chain to the larger TCR protein. TRBC1, as referred herein, includes any of the recombinant or naturally-occurring forms of TRBC1 or variants or homologs thereof that have or maintain TRBC1 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring TRBC1. In some embodiments, TRBC1 is substantially identical to the protein identified by the UniProt reference number P01850 or a variant or homolog having substantial identity thereto. [0416] “TRBC2,” also known as TRBC2, TCRBC2, T cell receptor beta constant 2, V_segment Translation Product, and T cell receptor beta constant 2, as referred herein, refers to a protein that in humans is encoded by the TRBC2 gene gene. TRBC2 contributes the beta chain to the larger TCR protein. TRBC2, as referred herein, includes any of the recombinant or naturally- occurring forms of TRBC2 or variants or homologs thereof that have or maintain TRBC2 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring TRBC2. In some embodiments, TRBC2 is substantially identical to the protein identified by the UniProt reference number A0A5B9 or a variant or homolog having substantial identity thereto. [0417] “CIITA,” also known as C2TA, CIITAIV, MHC2TA, NLRA, class II, major histocompatibility complex, transactivator, and class II major histocompatibility complex transactivator, as referred herein, refers to a protein essential for transcriptional activity of the HLA class II promoter. In some embodiments, CIITA mediates enhanced MHC class I transcription. In some embodiments, CIITA activates CD74 transcription. In some embodiments, CIITA exhibits intrinsic GTP-stimulated acetyltransferase activity. In some embodiments, CIITA exhibits serine/threonine protein kinase activity. CIITA, as referred herein, includes any of the recombinant or naturally-occurring forms of CIITA or variants or homologs thereof that have or maintain CIITA activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring CIITA. In some embodiments, CIITA is substantially identical to the protein identified by the UniProt reference number P33076 or a variant or homolog having substantial identity thereto. [0418] “CD70,” also known as CD27LG and TNFSF7, as referred herein, refers to a cytokine that is the ligand for CD27. The CD70-CD27 pathway plays an important role in the generation and maintenance of T cell immunity, in particular, during antiviral responses. Upon CD27 binding, CD70 induces the proliferation of co-stimulated T-cells and enhances the generation of cytolytic T-cells. CD70, as referred herein, includes any of the recombinant or naturally- occurring forms of CD70 or variants or homologs thereof that have or maintain CD70 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring CD70. In some embodiments, CD70 is substantially identical to the protein identified by the UniProt reference number P32970 or a variant or homolog having substantial identity thereto. [0419] The term “anti-tumor effect,” as used herein, refers to a biological effect which can be manifested by various means, including but not limited to, e.g., a decrease in tumor volume, a decrease in the number of tumor cells, a decrease in the number of metastases, an increase in life expectancy, decrease in tumor cell proliferation, decrease in tumor cell survival, or amelioration of various physiological symptoms associated with the cancerous condition. In some embodiments, an “anti-tumor effect” can also be manifested by the ability of the peptides, polynucleotides, cells and antibodies of the present disclosure in prevention of the occurrence of tumor in the first place. [0420] The term “autologous,” as used herein, refers to any material derived from the same individual to whom it is later to be re-introduced into the individual. [0421] The term “allogeneic” or, alternatively, “allogenic,” as used herein, refers to any material derived from a different animal of the same species or different patient as the individual to whom the material is introduced. Two or more individuals are said to be allogeneic to one another when the genes at one or more loci are not identical. In some aspects, allogeneic material from individuals of the same species may be sufficiently unlike genetically to interact antigenically. [0422] The term “xenogeneic” refers to a graft derived from an animal of a different species. [0423] The term “cancer” refers to a disease characterized by the rapid and uncontrolled growth of aberrant cells. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body. Examples of various cancers are described herein and include but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, lymphoma, leukemia, lung cancer and the like. [0424] The term “encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (e.g., rRNA, tRNA and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene, cDNA, or RNA, encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA. [0425] Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain one or more introns. [0426] The term “effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological or therapeutic result. [0427] The term “endogenous” refers to any material from or produced inside an organism, cell, tissue or system. [0428] The term “exogenous” refers to any material introduced from or produced outside an organism, cell, tissue or system. [0429] The term “expression” refers to the transcription and/or translation of a particular nucleotide sequence driven by a promoter. [0430] The term “functional disruption” refers to a physical or biochemical change to a specific (e.g., target) nucleic acid (e.g., gene, RNA transcript, of protein encoded thereby) that prevents its normal expression and/or behavior in the cell. In one embodiment, a functional disruption refers to a modification of the gene via a gene editing method. In one embodiment, a functional disruption prevents expression of a target gene (e.g., an endogenous gene). [0431] The term “transfer vector” refers to a composition of matter which comprises an isolated nucleic acid and which can be used to deliver the isolated nucleic acid to the interior of a cell. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Thus, the term “transfer vector” includes an autonomously replicating plasmid or a virus. The term should also be construed to further include non-plasmid and non-viral compounds which facilitate transfer of nucleic acid into cells, such as, for example, a polylysine compound, liposome, and the like. Examples of viral transfer vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors, retroviral vectors, lentiviral vectors, and the like. [0432] The term “expression vector” refers to a vector comprising a recombinant polynucleotide comprising expression control sequences operatively linked to a nucleotide sequence to be expressed. An expression vector comprises sufficient cis-acting elements for expression; other elements for expression can be supplied by the host cell or in an in vitro expression system. Expression vectors include all those known in the art, including cosmids, plasmids (e.g., naked or contained in liposomes) and viruses (e.g., lentiviruses, retroviruses, adenoviruses, and adeno- associated viruses) that incorporate the recombinant polynucleotide. [0433] The term “lentivirus” refers to a genus of the Retroviridae family. Lentiviruses are unique among the retroviruses in being able to infect non-dividing cells; they can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of a gene delivery vector. HIV, SIV, and FIV are all examples of lentiviruses. [0434] The term “lentiviral vector” refers to a vector derived from at least a portion of a lentivirus genome, including especially a self-inactivating lentiviral vector as provided in Milone et al., Mol. Ther.17(8): 1453-1464 (2009). Other examples of lentivirus vectors that may be used in the clinic, include but are not limited to, e.g., the LENTIVECTORTM gene delivery technology from Oxford BioMedica, the LENTIMAXTM vector system from Lentigen, and the like. Nonclinical types of lentiviral vectors are also available and would be known to one skilled in the art. [0435] The term “homologous” or “identity” refers to the subunit sequence identity between two polymeric molecules, e.g., between two nucleic acid molecules, such as, two DNA molecules or two RNA molecules, or between two polypeptide molecules. When a subunit position in both of the two molecules is occupied by the same monomeric subunit; e.g., if a position in each of two DNA molecules is occupied by adenine, then they are homologous or identical at that position. The homology between two sequences is a direct function of the number of matching or homologous positions; e.g., if half (e.g., five positions in a polymer ten subunits in length) of the positions in two sequences are homologous, the two sequences are 50% homologous; if 90% of the positions (e.g., 9 of 10), are matched or homologous, the two sequences are 90% homologous. [0436] “Humanized” forms of non-human (e.g., murine) antibodies are chimeric immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab’, F(ab’)2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. For the most part, humanized antibodies and antibody fragments thereof are human immunoglobulins (recipient antibody or antibody fragment) in which residues from a complementary-determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity, and capacity. In some instances, Fv framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, a humanized antibody/antibody fragment can comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. These modifications can further refine and optimize antibody or antibody fragment performance. In general, the humanized antibody or antibody fragment thereof will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non-human immunoglobulin and all or a significant portion of the FR regions are those of a human immunoglobulin sequence. The humanized antibody or antibody fragment can also comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature, 321: 522- 525, 1986; Reichmann et al., Nature, 332: 323-329, 1988; Presta, Curr. Op. Struct. Biol., 2: 593- 596, 1992. [0437] “Human” or “fully human” refers to an immunoglobulin, such as an antibody or antibody fragment, where the whole molecule is of human origin or consists of an amino acid sequence identical to a human form of the antibody or immunoglobulin. [0438] The term “isolated” means altered or removed from the natural state. For example, a nucleic acid or a peptide naturally present in a living animal is not “isolated,” but the same nucleic acid or peptide partially or completely separated from the coexisting materials of its natural state is “isolated.” An isolated nucleic acid or protein can exist in substantially purified form, or can exist in a non-native environment such as, for example, a host cell. [0439] In the context of the present disclosure, the following abbreviations for the commonly occurring nucleic acid bases are used. “A” refers to adenosine, “C” refers to cytosine, “G” refers to guanosine, “T” refers to thymidine, and “U” refers to uridine. [0440] The term “conservative sequence modifications” refers to amino acid modifications that do not significantly affect or alter the binding characteristics of the antibody or antibody fragment containing the amino acid sequence. Such conservative modifications include amino acid substitutions, additions and deletions. Modifications can be introduced into an antibody or antibody fragment of the present disclosure by standard techniques known in the art, such as site- directed mutagenesis and PCR-mediated mutagenesis. Conservative amino acid substitutions are ones in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine, tryptophan), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). Thus, one or more amino acid residues within a TFP of the present disclosure can be replaced with other amino acid residues from the same side chain family and the altered TFP can be tested using the functional assays described herein. [0441] The term “operably linked” or “transcriptional control” refers to functional linkage between a regulatory sequence and a heterologous nucleic acid sequence resulting in expression of the latter. For example, a first nucleic acid sequence is operably linked with a second nucleic acid sequence when the first nucleic acid sequence is placed in a functional relationship with the second nucleic acid sequence. For instance, a promoter is operably linked to a coding sequence if the promoter affects the transcription or expression of the coding sequence. Operably linked DNA sequences can be contiguous with each other and, e.g., where necessary to join two protein coding regions, are in the same reading frame. [0442] The term “parenteral” administration of an immunogenic composition includes, e.g., subcutaneous (s.c.), intravenous (i.v.), intramuscular (i.m.), or intrasternal injection, intratumoral, or infusion techniques. [0443] The term “nucleotide,” “nucleic acid” or “polynucleotide” refers to deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and polymers thereof in either single- or double- stranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and/or deoxyinosine residues (Batzer et al., Nucleic Acid Res.19:5081 (1991); Ohtsuka et al., J. Biol. Chem.260:2605-2608 (1985); and Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)). [0444] The terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein’s or peptide’s sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. A polypeptide includes a natural peptide, a recombinant peptide, or a combination thereof. [0445] The term “promoter” refers to a DNA sequence recognized by the transcription machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence. [0446] The term “promoter/regulatory sequence” refers to a nucleic acid sequence which is required for expression of a gene product operably linked to the promoter/regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements which are required for expression of the gene product. The promoter/regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner. [0447] The term “constitutive” promoter refers to a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell under most or all physiological conditions of the cell. [0448] The term “inducible” promoter refers to a nucleotide sequence which, when operably linked with a polynucleotide which encodes or specifies a gene product, causes the gene product to be produced in a cell substantially only when an inducer which corresponds to the promoter is present in the cell. [0449] The term “tissue-specific” promoter refers to a nucleotide sequence which, when operably linked with a polynucleotide encodes or specified by a gene, causes the gene product to be produced in a cell substantially only if the cell is a cell of the tissue type corresponding to the promoter. [0450] The terms “linker” and “flexible polypeptide linker” as used in the context of a scFv refers to a peptide linker that consists of amino acids such as glycine and/or serine residues used alone or in combination, to link variable heavy and variable light chain regions together. In one embodiment, the flexible polypeptide linker is a Gly/Ser linker and comprises the amino acid sequence (Gly-Gly-Gly-Ser)n, where n is a positive integer equal to or greater than 1. For example, n=1, n=2, n=3, n=4, n=5, n=6, n=7, n=8, n=9 and n=10. In one embodiment, the flexible polypeptide linkers include, but are not limited to, (Gly4Ser)4 or (Gly4Ser)3. In another embodiment, the linkers include multiple repeats of (Gly2Ser), (GlySer) or (Gly3Ser). Also included within the scope of the present disclosure are linkers described in WO2012/138475 (incorporated herein by reference). In some instances, the linker sequence comprises (G4S)n, wherein n=2 to 5. In some instances, the linker sequence comprises (G4S)n, wherein n=1 to 3. [0451] As used herein, a 5’ cap (also termed an RNA cap, an RNA 7-methylguanosine cap or an RNA m7G cap) is a modified guanine nucleotide that has been added to the “front” or 5’ end of a eukaryotic messenger RNA shortly after the start of transcription. The 5’ cap consists of a terminal group which is linked to the first transcribed nucleotide. Its presence is critical for recognition by the ribosome and protection from RNases. Cap addition is coupled to transcription, and occurs co-transcriptionally, such that each influences the other. Shortly after the start of transcription, the 5’ end of the mRNA being synthesized is bound by a cap- synthesizing complex associated with RNA polymerase. This enzymatic complex catalyzes the chemical reactions that are required for mRNA capping. Synthesis proceeds as a multi-step biochemical reaction. The capping moiety can be modified to modulate functionality of mRNA such as its stability or efficiency of translation. [0452] As used herein, “in vitro transcribed RNA” refers to RNA, preferably mRNA, which has been synthesized in vitro. Generally, the in vitro transcribed RNA is generated from an in vitro transcription vector. The in vitro transcription vector comprises a template that is used to generate the in vitro transcribed RNA. [0453] As used herein, a “poly(A)” is a series of adenosines attached by polyadenylation to the mRNA. In the preferred embodiment of a construct for transient expression, the polyA is between 50 and 5000, preferably greater than 64, more preferably greater than 100, most preferably greater than 300 or 400. Poly(A) sequences can be modified chemically or enzymatically to modulate mRNA functionality such as localization, stability or efficiency of translation. [0454] As used herein, “polyadenylation” refers to the covalent linkage of a polyadenylyl moiety, or its modified variant, to a messenger RNA molecule. In eukaryotic organisms, most messenger RNA (mRNA) molecules are polyadenylated at the 3’ end. The 3’ poly(A) tail is a long sequence of adenine nucleotides (often several hundred) added to the pre-mRNA through the action of an enzyme, polyadenylate polymerase. In higher eukaryotes, the poly(A) tail is added onto transcripts that contain a specific sequence, the polyadenylation signal. The poly(A) tail and the protein bound to it aid in protecting mRNA from degradation by exonucleases. Polyadenylation is also important for transcription termination, export of the mRNA from the nucleus, and translation. Polyadenylation occurs in the nucleus immediately after transcription of DNA into RNA, but additionally can also occur later in the cytoplasm. After transcription has been terminated, the mRNA chain is cleaved through the action of an endonuclease complex associated with RNA polymerase. The cleavage site is usually characterized by the presence of the base sequence AAUAAA near the cleavage site. After the mRNA has been cleaved, adenosine residues are added to the free 3’ end at the cleavage site. [0455] As used herein, “transient” refers to expression of a non-integrated transgene for a period of hours, days or weeks, wherein the period of time of expression is less than the period of time for expression of the gene if integrated into the genome or contained within a stable plasmid replicon in the host cell. [0456] The term “signal transduction pathway” refers to the biochemical relationship between a variety of signal transduction molecules that play a role in the transmission of a signal from one portion of a cell to another portion of a cell. The phrase “cell surface receptor” includes molecules and complexes of molecules capable of receiving a signal and transmitting signal across the membrane of a cell. [0457] The term “subject” is intended to include living organisms in which an immune response can be elicited (e.g., mammals, human). [0458] The term, a “substantially purified” cell refers to a cell that is essentially free of other cell types. A substantially purified cell also refers to a cell which has been separated from other cell types with which it is normally associated in its naturally occurring state. In some instances, a population of substantially purified cells refers to a homogenous population of cells. In other instances, this term refers simply to cell that have been separated from the cells with which they are naturally associated in their natural state. In some aspects, the cells are cultured in vitro. In other aspects, the cells are not cultured in vitro. [0459] The term “therapeutic” as used herein means a treatment. A therapeutic effect is obtained by reduction, suppression, remission, or eradication of a disease state. [0460] The term “prophylaxis” as used herein means the prevention of or protective treatment for a disease or disease state. [0461] In the context of the present disclosure, “tumor antigen” or “hyperproliferative disorder antigen” or “antigen associated with a hyperproliferative disorder” refers to antigens that are common to specific hyperproliferative disorders. In some embodiments, the hyperproliferative disorder antigens of the present disclosure are derived from, cancers including but not limited to primary or metastatic melanoma, thymoma, lymphoma, sarcoma, lung cancer, liver cancer, NHL, leukemias, uterine cancer, cervical cancer, bladder cancer, kidney cancer and adenocarcinomas such as breast cancer, prostate cancer, ovarian cancer, pancreatic cancer, and the like. [0462] The term “transfected” or “transformed” or “transduced” refers to a process by which exogenous nucleic acid is transferred or introduced into the host cell. A “transfected” or “transformed” or “transduced” cell is one which has been transfected, transformed or transduced with exogenous nucleic acid. The cell includes the primary subject cell and its progeny. [0463] The term “specifically binds,” refers to an antibody, an antibody fragment or a specific ligand, which recognizes and binds a cognate binding partner (e.g., CD19) present in a sample, but which does not necessarily and substantially recognize or bind other molecules in the sample. [0464] As used herein, the term “meganuclease” refers to an endonuclease that binds double- stranded DNA at a recognition sequence that is greater than 12 base pairs. In some embodiments, the recognition sequence for a meganuclease of the present disclosure is 22 base pairs. In some embodiments, a meganuclease may be an endonuclease that is derived from I-Crel and may refer to an engineered variant of I-Crel that has been modified relative to natural I-Crel with respect to, for example, DNA-binding specificity, DNA cleavage activity, DNA-binding affinity, or dimerization properties. Methods for producing such modified variants of I-Crel are known in the art (e.g., WO 2007/047859). In some embodiments, a meganuclease binds to double-stranded DNA as a heterodimer or as a “single-chain meganuclease” in which a pair of DNA-binding domains are joined into a single polypeptide using a peptide linker. The term “homing endonuclease” is synonymous with the term “meganuclease.” In some embodiments, meganucleases are substantially non-toxic when expressed in cells, particularly in human T cells, such that cells may be transfected and maintained at 37°C without observing deleterious effects on cell viability or significant reductions in meganuclease cleavage activity when measured using the methods described herein. [0465] As used herein, the term “single-chain meganuclease” refers to a polypeptide comprising a pair of nuclease subunits joined by a linker. A single-chain meganuclease has the organization: N-terminal subunit - Linker - C-terminal subunit. In some embodiments, the two meganuclease subunits may generally be non-identical in amino acid sequence and may recognize non-identical DNA sequences. Thus, in some embodiments, single-chain meganucleases typically cleave pseudo-palindromic or non-palindromic recognition sequences. In some embodiments, a single- chain meganuclease may be referred to as a “single-chain heterodimer” or “single-chain heterodimeric meganuclease” although it is not, in fact, dimeric. For clarity, unless otherwise specified, the term “meganuclease” can refer to a dimeric or single-chain meganuclease. [0466] As used herein, the term “TALEN” refers to an endonuclease comprising a DNA-binding domain comprising 16-22 TAL domain repeats fused to any portion of the Fokl nuclease domain. [0467] As used herein, the term “Compact TALEN” refers to an endonuclease comprising a DNA-binding domain with 16-22 TAL domain repeats fused in any orientation to any catalytically active portion of nuclease domain of the I-Tevl homing endonuclease. [0468] As used herein, the term “CRISPR” refers to a caspase-based endonuclease comprising a caspase, such as Cas9, and a guide RNA that directs DNA cleavage of the caspase by hybridizing to a recognition site in the genomic DNA. [0469] As used herein, the term “megaTAL” refers to a single-chain nuclease comprising a transcription activator-like effector (TALE) DNA binding domain with an engineered, sequence- specific homing endonuclease. [0470] As is used herein, the terms “T cell receptor” and “T cell receptor complex” are used interchangeably to refer to a molecule found on the surface of T cells that is, in general, responsible for recognizing antigens. The TCR comprises a heterodimer consisting of a TCR alpha and TCR beta chain in 95% of T cells, whereas 5% of T cells have TCRs consisting of TCR gamma and TCR delta chains. The TCR further comprises one or more of CD3ε, CD3γ, and CD3δ. In some embodiments, the TCR comprises CD3ε. In some embodiments, the TCR comprises CD3γ. In some embodiments, the TCR comprises CD3δ. In some embodiments, the TCR comprises CD3ζ. Engagement of the TCR with antigen, e.g., with antigen and MHC, results in activation of its T cells through a series of biochemical events mediated by associated enzymes, co-receptors, and specialized accessory molecules. In some embodiments, the constant domain of human TCR alpha has a sequence of SEQ ID NO:142. In some embodiments, the constant domain of human TCR alpha has an IgC domain having a sequence of SEQ ID NO:143, a transmembrane domain having a sequence of SEQ ID NO:144, and an intracellular domain having a sequence of SS. In some embodiments, the constant domain of murine TCR alpha has a sequence of SEQ ID NO:147. In some embodiments, the constant domain of murine TCR alpha has a transmembrane domain having a sequence of SEQ ID NO:144, and an intracellular domain having a sequence of SS. In some embodiments, the constant domain of human TCR beta has a sequence of SEQ ID NO:148. In some embodiments, the constant domain of human TCR beta has an IgC domain having a sequence of SEQ ID NO:149, a transmembrane domain having a sequence of SEQ ID NO:150, and an intracellular domain having a sequence of SEQ ID NO:151. In some embodiments, the constant domain of murine TCR beta has a sequence of SEQ ID NO:152. In some embodiments, the constant domain of murine TCR beta has a transmembrane domain having a sequence of SEQ ID NO:152, and an intracellular domain having a sequence of SEQ ID NO:153. In some embodiments, the constant domain of human TCR delta has a sequence of SEQ ID NO:243. In some embodiments, the constant domain of human TCR delta has an IgC domain having a sequence of SEQ ID NO:265, a transmembrane domain having a sequence of SEQ ID NO:158, and an intracellular domain having a sequence of L. In some embodiments, the constant domain of human TCR gamma has a sequence of SEQ ID NO:21. In some embodiments, the constant domain of human TCR gamma has an IgC domain having a sequence of SEQ ID NO:155, a transmembrane domain having a sequence of SEQ ID NO:156, and an intracellular domain having a sequence of SEQ ID NO:157. [0471] In some embodiments, human CD3 epsilon has a sequence of SEQ ID NO:258. In some embodiments, human CD3 epsilon has an extracellular domain having a sequence of SEQ ID NO:126, a transmembrane domain having a sequence of SEQ ID NO:127, and an intracellular domain, e.g., an intracellular signaling domain, having a sequence of SEQ ID NO:128. In some embodiments, human CD3 delta has a sequence of SEQ ID NO:136. In some embodiments, human CD3 delta has an extracellular domain having a sequence of SEQ ID NO:138, a transmembrane domain having a sequence of SEQ ID NO:139, and an intracellular domain, e.g., an intracellular signaling domain, having a sequence of SEQ ID NO:140. In some embodiments, human CD3 gamma has a sequence of SEQ ID NO:130. In some embodiments, human CD3 gamma has an extracellular domain having a sequence of SEQ ID NO:132, a transmembrane domain having a sequence of SEQ ID NO:133, and an intracellular domain, e.g., an intracellular signaling domain, having a sequence of SEQ ID NO:134. [0472] Ranges: throughout this disclosure, various aspects of the present disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. As another example, a range such as 95-99% identity, includes something with 95%, 96%, 97%, 98% or 99% identity, and includes subranges such as 96-99%, 96-98%, 96-97%, 97-99%, 97-98% and 98-99% identity. This applies regardless of the breadth of the range. [0473] Provided herein are compositions of matter and methods of use for the treatment of a disease such as cancer, using modified immune cells comprising a T cell receptors (TCR) fusion protein (TFP) and an RNA interference (RNAi) agent or a sequence encoding the RNAi agent as described herein, wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with alloreactivity. In some embodiments, the modified immune cells also comprise a TCR constant domain. In some embodiments, the modified T cell also has a functionally disrupted endogenous TCR subunit. As used herein, a “T cell receptor (TCR) fusion protein” or “TFP” includes a recombinant polypeptide derived from the various polypeptides comprising the TCR that is generally capable of i) binding to a surface antigen on target cells and ii) interacting with other polypeptide components of the intact TCR complex, typically when co-located in or on the surface of a T cell. As provided herein, TFPs provide substantial benefits as compared to Chimeric Antigen Receptors. The term “Chimeric Antigen Receptor” or alternatively a “CAR” refers to a recombinant polypeptide comprising an extracellular antigen binding domain in the form of, e.g., a single domain antibody or scFv, a transmembrane domain, and cytoplasmic signaling domains (also referred to herein as “intracellular signaling domains”) comprising a functional signaling domain derived from a stimulatory molecule as defined below. Generally, the central intracellular signaling domain of a CAR is derived from the CD3 zeta chain that is normally found associated with the TCR complex. The CD3 zeta signaling domain can be fused with one or more functional signaling domains derived from at least one co-stimulatory molecule such as 4-1BB (i.e., CD137), CD27 and/or CD28. RNA interference Agent [0474] RNA interference (RNAi) or RNA silencing refers to a process by which gene expression is negatively regulated by non-coding RNAs such as microRNAs. The negative regulation can result from one or more of three possible mechanisms: (1) by repressing the translation of target mRNAs, (2) through deadenylation and destabilization of transcripts, and (3) through cleavage and degradation of mRNAs. RNAi is normally triggered by double-stranded RNA (dsRNA) or endogenous microRNA precursors (pri-miRNAs/pre-miRNAs). [0475] The production of endogenous microRNA molecules can begin with the transcription of a primary miRNA (pri-mRNA) from an RNA polymerase II (Pol II) promoter. Each pri-miRNA can contain from one to six pre-miRNAs. Pre-miRNAs can be hairpin loop structures composed of about 70 nucleotides, with each hairpin being flanked by sequences necessary for efficient processing. The enzyme Drosha can liberate hairpins from the pri-miRNAs by cleaving RNA about 11 nucleotides from the hairpin base. Pre-miRNAs that are generated by Drosha cleavage comprise a 2 nucleotide overhang at the 3' end. This 2 nucleotide overhang can be bound by the Exportin-5 protein, which mediates export of the pre-miRNA from the nucleus into the cytoplasm. In the cytoplasm, pre-miRNA hairpins are cleaved by Dicer through interactions with the 5’ and 3’ ends of the hairpin. Dicer can cleave the pre-miRNA hairpin in the loop region to produce an imperfect miRNA:miRNA duplex, which is about 22 nucleotides in length. A single strand of the miRNA:miRNA duplex (mature miRNA) can be incorporated into the RNA- induced silencing complex (RISC) where the miRNA and its mRNA target interact. [0476] Since its discovery, RNAi has emerged as a powerful genetic tool for suppressing gene expression in mammalian cells. Gene knockdown can be achieved by expression of synthetic short hairpin RNAs (shRNAs) that mimic pre-miRNAs and are processed by Dicer and fed into the RISC. However, as described herein, shRNAs may not allow for prolonged reduction of protein expression in immune cells. In contrast, expression of the pri-microRNA-adapted shRNA (pri-shRNAmiR) molecules of the present invention result in persistent reduction of protein expression and reduced toxicity effects. The pri-shRNAmiR molecules mimic pri-miRNA molecules in that they comprise a hairpin flanked by sequences necessary for efficient processing, and can be processed by the Drosha enzyme into pri-miRNAs, exported into the cytoplasm, and cleaved by Dicer, after which the mature shRNAmiR can enter the RISC. [0477] The present disclosure provides genetically-modified immune cells expressing an shRNA or a pri-shRNAmiR molecule that reduces the abundance of an endogenous protein. [0478] The pri-shRNAmiR molecule can comprise a microRNA scaffold in that the structure of the pri-shRNAmiR molecule can mimic that of a naturally-occurring microRNA (or pri-miRNA or pre- miRNA) or a variant thereof. Sequences of microRNAs (and pri-miRNAs and pre- miRNAs) are known in the art. Non-limiting examples of suitable miR scaffolds for the presently disclosed pri-shRNAmiRs include miR-30 (e.g., miR-30a), miR-15, miR-16, miR-155, miR-22, miR-103, eSIBR, miR-196a2, a scaffold sequence from the miR-106a~363 cluster, and miR-107. The miR scaffold can be of mouse or human origin. In particular embodiments, the pri- shRNAmiR used in the presently disclosed compositions and methods comprises eSIBR scaffold. The eSIBR scaffold is a synthetically-derived variant of miR-155 and its genesis is described in Fowler et al., NAR 201644(5), which is incorporated by reference in its entirety. [0479] The presently disclosed pri-shRNAmiR molecules can comprise the following domains in the 5' to 3' direction: (a) a 5' pri-miR scaffold domain; (b) a 5' pri-miR basal stem domain; (c) a guide or passenger strand; (d) a pri-miR loop domain; (e) a guide or passenger strand; (f) a 3' pri- miR basal stem domain; and (g) a 3' pri-miR scaffold domain. The miR scaffold domains and basal stem domains flank the miRNA stem-loop (the pre-shRNAmiR) and are referred to herein as microRNA flanking sequences that comprise the microRNA processing elements (the minimal nucleic acid sequences which contribute to the production of mature microRNA from primary microRNA or precursor microRNA). Often these elements are located within a 40 nucleotide sequence that flanks a microRNA stem-loop structure. In some instances, the microRNA processing elements are found within a stretch of nucleotide sequences of between 5 and 4,000 nucleotides in length that flank a microRNA stem-loop structure. [0480] In some embodiments, the G/C content of the shRNAmiR is at least 5%, at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, at least 35%, at least 40%, at least 45%, at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, or at least 90 %. In some embodiments, the G/C content of the shRNAmiR is at most 95%, at most 90%, at most 85%, at most 80%, at most 75%, at most 70%, at most 65%, at most 60%, at most 55%, at most 50%, at most 45%, at most 40%, at most 35%, at most 30%, at most 25%, or at most 20%. In some embodiments, the G/C content of the shRNAmiR is between 5% and 95%, 10% and 90%, 15% and 85%, 20% and 80%, 25% and 75%, 30% and 70%, or 40% and 60%. In some embodiments, the G/C content of the shRNAmiR is between 30% and 35%, 30% and 40%, 30% and 45%, 30% and 50%, 30% and 55%, 30% and 60%, 30% and 65%, 30% and 70%, 30% and 80%, or 30% and 90%. In some embodiments, the G/C content of the shRNAmiR is between 45% and 50%, 40% and 50%, 35% and 50%, 30% and 50%, 25% and 50%, 20% and 50%, 15% and 50%, 10% and 50%, or 5% and 50%. In some embodiments, the G/C content of the shRNAmiR is between 25% and 55%, 20% and 60%, 15% and 65%, or 10% and 70%. In some embodiments, the G/C content of the shRNAmiR is between 40% and 41%, 39% and 42%, 38% and 43%, 37% and 44%, 36% and 45%, 35% and 46%, 34% and 47%, 33% and 48%, 32% and 49%, 31% and 50%, 30% and 51%, 29% and 52%, 28% and 53%, 27% and 54%, 26% and 55%, 25% and 56%, 24% and 57%, 23% and 58%, 22% and 59%, 21% and 60%, 20% and 61%, 19% and 62%, 18% and 63%, 17% and 64%, 16% and 65%,15% and 66%, 14% and 67%, 13% and 68%,12% and 69%, or 11% and 70%. [0481] In some embodiments, the pri-shRNAmiR is at least about 5, about 6, about 7, about 8, about 9, about 10, about 15, about 20, about 25, about 30, about 35, about 40, about 45, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 150, about 200, about 250, about 300, about 350, about 400, about 450, about 500, about 550, about 600, about 650, about 700, about 750, about 800, about 850, about 900, about 1000, about 1100, about 1200, about 1300, about 1400, about 1500, about 1600, about 1700, about 1800, about 1900, about 2000, about 2100, about 2200, about 2300, about 2400, about 2500, about 2600, about 2700, about 2800, about 2900, about 3100, about 3200, about 3300, about 3400, about 3500, about 3600, about 3700, about 3800, about 3900, about 4100, about 4200, about 4300, about 4400, about 4500, about 4600, about 4700, about 4800, about 4900, about 5100, about 5200, about 5300, about 5400, about 5500, about 5600, about 5700, about 5800, about 5900, about 6100, about 6200, about 6300, about 6400, about 6500, about 6600, about 6700, about 6800, about 6900, about 7100, about 7200, about 7300, about 7400, about 7500, about 7600, about 7700, about 7800, about 7900, about 8100, about 8200, about 8300, about 8400, about 8500, about 8600, about 8700, about 8800, about 8900, about 9100, about 9200, about 9300, about 9400, about 9500, about 9600, about 9700, about 9800, about 9900 nucleotides in length, and any integer therein between. [0482] In some embodiments, the pri-shRNAmiR is at most about 1000, about 9900, about 9800, about 9700, about 9600, about 9500, about 9400, about 9300, about 9200, about 9100, about 9000, about 8900, about 8800, about 8700, about 8600, about 8500, about 8400, about 8300, about 8200, about 8100, about 8000, about 7900, about 7800, about 7700, about 7600, about 7500, about 7400, about 7300, about 7200, about 7100, about 7000, about 6900, about 6800, about 6700, about 6600, about 6500, about 6400, about 6300, about 6200, about 6100, about 6000, about 5900, about 5800, about 5700, about 5600, about 5500, about 5400, about 5300, about 5200, about 5100, about 5000, about 4900, about 4800, about 4700, about 4600, about 4500, about 4400, about 4300, about 4200, about 4100, about 4000, about 3900, about 3800, about 3700, about 3600, about 3500, about 3400, about 3300, about 3200, about 3100, about 3000, about 2900, about 2800, about 2700, about 2600, about 2500, about 2400, about 2300, about 2200, about 2100, about 2000, about 1900, about 1800, about 1700, about 1600, about 1500, about 1400, about 1300, about 1200, about 1100, about 1000, about 950, about 900, about 850, about 800, about 750, about 700, about 650, about 600, about 550, about 500, about 450, about 400, about 350, about 300, about 200, about 150, about 100 nucleotides in length, and any integer therein between. [0483] In some embodiments, the pri-shRNAmiR is from about 20 to about 300, from about 30 to about 300, from about 40 to about 300, from about 50 to about 300, from about 60 to about 300, from about 60 to about 300, from about 70 to about 300, from about 80 to about 300, from about 90 to about 300, from about 100 to about 300, from about 110 to about 300, from about 120 to about 300, from about 130 to about 300, from about 140 to about 300, from about 150 to about 300, from about 160 to about 300, from about 170 to about 300, from about 180 to about 300, from about 190 to about 300, from about 200 to about 300, from about 210 to about 300, from about 220 to about 300, from about 230 to about 300, from about 240 to about 300, from about 250 to about 300, from about 260 to about 300, from about 270 to about 300, from about 280 to about 300, from about 290 to about 300 nucleotides in length, and any integer therein between. [0484] In some embodiments, the pri-shRNAmiR is from about 100 to about 500, from about 100 to about 490, from about 100 to about 480, from about 100 to about 470, from about 100 to about 460, from about 100 to about 450, from about 100 to about 440, from about 100 to about 430, from about 100 to about 420, from about 100 to about 410, from about 100 to about 400, from about 100 to about 390, from about 100 to about 380, from about 100 to about 370, from about 100 to about 360, from about 100 to about 350, from about 100 to about 340, from about 100 to about 330, from about 100 to about 320, from about 100 to about 310, from about 100 to about 300, from about 100 to about 290, from about 100 to about 280, from about 100 to about 270, from about 100 to about 260, from about 100 to about 250, from about 100 to about 240, from about 100 to about 230, from about 100 to about 220, from about 100 to about 210, from about 100 to about 200, from about 100 to about 190, from about 100 to about 180, from about 100 to about 170, from about 100 to about 160, from about 100 to about 150, from about 100 to about 140, from about 100 to about 130, from about 100 to about 120, from about 100 to about 110 nucleotides in length, and any integer therein between. [0485] In some embodiments, the pri-shRNAmiR is from about 150 to about 170, from about 140 to about 180, from about 130 to about 190, from about 120 to about 200, from about 110 to about 210, from about 100 to about 220, from about 90 to about 230, from about 80 to about 240, from about 70 to about 250, from about 60 to about 260, from about 50 to about 270, from about 40 to about 280, from about 30 to about 290, from about 20 to about 300 nucleotides in length, and any integer therein between. [0486] In some embodiments, the miRNA flanking sequences are about 3 to about 4,000 nt in length and can be present on either or both the 5' and 3' ends of the pri-shRNAmiR molecule. In other embodiments, the minimal length of the microRNA flanking sequence of the pri- shRNAmiR molecule is about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 150, about 200, and any integer therein between. In other embodiments, the maximal length of the microRNA flanking sequence of the pri-shRNAmiR molecule is about 2,000, about 2,100, about 2,200, about 2,300, about 2,400, about 2,500, about 2,600, about 2,700, about 2,800, about 2,900, about 3,000, about 3,100, about 3,200, about 3,300, about 3,400, about 3,500, about 3,600, about 3,700, about 3,800, about 3,900, about 4,000, and any integer therein between. [0487] In some embodiments, the 5’ miRNA flanking sequence of the pri-shRNAmiR molecule are about 3 to about 500 nt in length. In other embodiments, the minimal length of the 5’ miRNA flanking sequence of the pri-shRNAmiR molecule is about 3, about 4, about 5 about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 31, about 32, about 33, about 34, about 35, about 36, about 37, about 38, about 39, about 40, about 41, about 42, about 43, about 44, about 45, about 46, about 47, about 48, about 49, about 50, about 55, about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, and any integer therein between. In other embodiments, the maximal length of the 5’ miRNA flanking sequence of the pri-shRNAmiR molecule is about 500, about 450, about 400, about 350 , about 300, about 290, about 280, about 270, about 260, about 250, about 240, about 230, about 220, about 210, about 200, about 190, about 180, about 170, about 160, about 150, about 140, about 130, about 120, about 110, about 100, about 90, about 85, about 80, about 75, about 70, about 65, about 60, about 59, about 58, about 57, about 56, about 55, about 54, about 53, about 52, about 51, about 50, about 49, about 48, about 47, about 46, about 45, about 44, about 43, about 42, about 41, about 40, about 39, about 38, about 37, about 36, about 35, about 34, about 33, about 32, about 31, about 30, about 29, about 28, about 27, about 26, about 25, about 24, about 23, about 22, about 21, about 20, about 19, about 18, about 17, about 16, about 15, and any integer therein between. [0488] In some embodiments, the 3’ miRNA flanking sequence of the pri-shRNAmiR molecule are about 3 to about 800 nt in length. In other embodiments, the minimal length of the 3’ miRNA flanking sequence of the pri-shRNAmiR molecule is about 3, about 4, about 5 about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 31, about 32, about 33, about 34, about 35, about 36, about 37, about 38, about 39, about 40, about 41, about 42, about 43, about 44, about 45, about 46, about 47, about 48, about 49, about 50, about 51, about 52, about 53, about 54, about 55, about 56, about 57, about 58, about 59, about 60, about 61, about 62, about 63, about 64, about 65, about 66, about 67, about 68, about 69, about 70, about 71, about 72, about 73, about 74, about 75, about 76, about 77, about 78, about 79, about 80, about 81, about 82, about 83, about 84, about 85, about 86, about 87, about 88, about 89, about 90, about 91, about 92, about 93, about 94, about 95, about 96, about 97, about 98, about 99, about 100, about 105, about 110, about 115, about 120, about 125, about 130, about 135, about 140, about 145, about 150, about 155, about 160, about 165, about 170, about 175, about 180, about 185, about 190, about 195, about 200, and any integer therein between. In other embodiments, the maximal length of the 3’ miRNA flanking sequence of the pri-shRNAmiR molecule is about 800, about 750, about 700, about 650, about 600, about 550, about 500, about 450, about 400, about 390, about 380, about 370, about 360, about 350, about 340, about 330, about 320, about 310, about 300, about 290, about 280, about 270, about 260, about 250, about 240, about 230, about 220, about 210, about 200, about 190, about 180, about 170, about 160, about 150, about 140, about 130, about 120, about 110, about 100, about 99, about 98, about 97, about 96, about 95, about 94, about 93, about 92, about 91, about 90, about 89, about 88, about 87, about 86, about 85, about 84, about 83, about 82, about 81, about 80, about 79, about 78, about 77, about 76, about 75, about 74, about 73, about 72, about 71, about 70, about 69, about 68, about 67, about 66, about 65, about 64, about 63, about 62, about 61, about 60, about 59, about 58, about 57, about 56, about 55, about 54, about 53, about 52, about 51, about 50, and any integer therein between. [0489] The microRNA flanking sequences may be native microRNA flanking sequences or artificial microRNA flanking sequences. A native microRNA flanking sequence is a nucleotide sequence that is ordinarily comprised within naturally existing systems with microRNA sequences (i.e., these sequences are found within the genomic sequences surrounding the minimal microRNA hairpin in vivo). Artificial microRNA flanking sequences are nucleotides sequences that are not found to be flanking microRNA sequences in naturally existing systems. The artificial microRNA flanking sequences may be flanking sequences found naturally in the context of other microRNA sequences. Alternatively, they may be composed of minimal microRNA processing elements which are found within naturally occurring flanking sequences and inserted into other random nucleic acid sequences that do not naturally occur as flanking sequences or only partially occur as natural flanking sequences. [0490] In some embodiments, the 5' pri-miR scaffold domain is about 10 to about 150 nucleotides in length, including but not limited to about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, and about 150 nucleotides long. In some of these embodiments, the 5' pri-miR scaffold domain is about 15, 16, or 17 nucleotides in length. In some of these embodiments, the 5' pri- miR scaffold domain is about 15 nucleotides in length. In some of these embodiments, the 5' pri- miR scaffold domain is about 16 nucleotides in length. In some of these embodiments, the 5' pri- miR scaffold domain is about 17 nucleotides in length. In particular embodiments, the 5' pri-miR scaffold domain has at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or more sequence identity to the sequence set forth as SEQ ID NO:160. [0491] In certain embodiments, the 5' pri-miR scaffold domain has the sequence set forth as SEQ ID NO:160. [0492] The 5' pri-miR basal stem domain of the shRNAmiR can be about 5 to about 30 nucleotides in length in some embodiments, including but not limited to about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, and about 30 nucleotides long. In some of these embodiments, the 5' pri-miR basal stem domain is about 11 nucleotides in length. In some of these embodiments, the 5' pri-miR basal stem domain is about 12 nucleotides in length. In some of these embodiments, the 5' pri-miR basal stem domain is about 13 nucleotides in length. In particular embodiments, the 5' pri-miR basal stem domain has at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or more sequence identity to the sequence set forth as SEQ ID NO:161. In certain embodiments, the 5' pri-miR basal stem domain has the sequence set forth as SEQ ID NO:161. [0493] The shRNAmiR molecules of the presently disclosed compositions and methods comprise a stem-loop structure, wherein the stem is comprised of the hybridized passenger and guide strands and the loop is single-stranded. The pri-miR loop domain can be derived from a naturally-occurring pre-microRNA or pri-microRNA loop sequence or a variant thereof. In some embodiments, the pri-miR loop domain has the sequence of a loop domain from any one of miR- 30 (e.g., miR-30a), miR-15, miR-16, miR-155, miR-22, miR-103, eSIBR, and miR-107. In particular embodiments, the shRNAmiR comprises a miR-30a loop domain, the sequence of which is set forth as SEQ ID NO:162. [0494] In some embodiments, the pri-shRNAmiR comprises an enhanced synthetic inhibitory BIC/miR-155 RNA (eSIBR) scaffold. In some embodiments, eSIBR comprises 5' pri-miR scaffold domain, 5' pri-miR basal stem domain, pri-miR loop domain, 3' pri-miR basal stem domain, 3' pri-miR scaffold domain, or any combination thereof. In some embodiments, eSIBR comprises a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:160, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:161, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:162, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:163, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:164, or any combination thereof. In some embodiments, eSIBR comprises the nucleic acid sequence of SEQ ID NO:160, the nucleic acid sequence of SEQ ID NO:161, the nucleic acid sequence of SEQ ID NO:162, the nucleic acid sequence of SEQ ID NO:163, the nucleic acid sequence of SEQ ID NO:164, or any combination thereof. In some embodiments, eSIBR comprises a guide strand sequence, a loop sequence, a passenger strand sequence, or any combination thereof. In some embodiments, eSIBR comprises a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, or any combination thereof. In some embodiments, eSIBR comprises the nucleic acid sequence of SEQ ID NO:284, the nucleic acid sequence of SEQ ID NO:285, the nucleic acid sequence of SEQ ID NO:286, or any combination thereof. In some embodiments, eSIBR comprises a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168. In some embodiments, eSIBR comprises the nucleic acid sequence of SEQ ID NO:168. In some embodiments, the terms eSIBR, pri- shRNAmiR, and shRNA are interchangeably used. [0495] In certain embodiments, the pri-miR loop domain is about 5 to about 30 nucleotides in length, including but not limited to about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, and about 30 nucleotides long. In some of these embodiments, the pri-miR loop domain is about 16 nucleotides in length. In some of these embodiments, the pri-miR loop domain is about 17 nucleotides in length. In some of these embodiments, the pri-miR loop domain is about 18 nucleotides in length. In particular embodiments, the pri-miR loop domain has at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or more sequence identity to the sequence set forth as SEQ ID NO:162. In certain embodiments, the pri-miR loop domain has the sequence set forth as SEQ ID NO:162. [0496] The 3' pri-miR basal stem domain of the shRNAmiR can be about 5 to about 30 nucleotides in length in some embodiments, including but not limited to about 5, about 6, about 7, about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, and about 30 nucleotides long. In some of these embodiments, the 3' pri-miR basal stem domain is about 12 nucleotides in length. In some of these embodiments, the 3' pri-miR basal stem domain is about 13 nucleotides in length. In some of these embodiments, the 3' pri-miR basal stem domain is about 14 nucleotides in length. In particular embodiments, the 3' pri-miR basal stem domain has at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or more sequence identity to the sequence set forth as SEQ ID NO:163. In certain embodiments, the 3' pri-miR basal stem domain has the sequence set forth as SEQ ID NO:163. [0497] In some embodiments, the 3' pri-miR scaffold domain is about 10 to about 150 nucleotides in length, including but not limited to about 10, about 20, about 30, about 40, about 50, about 60, about 70, about 80, about 90, about 100, about 110, about 120, about 130, about 140, or about 150 nucleotides long. In some of these embodiments, the 3' pri-miR scaffold domain is about 45-55 nucleotides in length. In some of these embodiments, the 3' pri-miR scaffold domain is about 48 nucleotides in length. In some of these embodiments, the 3' pri-miR scaffold domain is about 49 nucleotides in length. In some of these embodiments, the 3' pri-miR scaffold domain is about 50 nucleotides in length. In particular embodiments, the 3' pri-miR scaffold domain has at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99% or more sequence identity to the sequence set forth as SEQ ID NO:164. In certain embodiments, the 3' pri-miR scaffold domain has the sequence set forth as SEQ ID NO:164.. [0498] The guide strand of the shRNAmiR can be the sequence that targets the mRNA, leading to reduction in abundance of the protein encoded by the mRNA. After the guide strand binds to its target mRNA, RISC either degrades the target transcript and/or prevents the target transcript from being loaded into the ribsome for translation. The guide strand is of sufficient complementarity with the target mRNA in order to lead to reduced expression of the target mRNA. In some embodiments, the guide strand is at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 98%, at least about 99% or 100% complementary to the target mRNA sequence. [0499] In certain embodiments, the guide strand hybridizes with the target mRNA within a coding sequence. The guide strand can comprise 1, 2, 3, 4, 5, or more mismatching nucleotides with the target mRNA sequence. In other embodiments, the guide strand hybridizes with the target mRNA in a non-coding region, such as a 5' or 3' untranslated region (UTR). In some embodiments, the guide strand is about 15 to about 25 nucleotides in length, including but not limited to about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, and about 25 nucleotides long. In some of these embodiments, the guide strand is about 22 nucleotides in length. In particular embodiments wherein the shRNA sequence from which the shRNAmiR is derived is less than 22 nucleotides in length, which is the length of most naturally-occurring microRNAs, an additional nucleotide is added to the shRNA sequence and in certain embodiments, this additional nucleotide is one that is complementary with the corresponding position within the target mRNA. [0500] The passenger strand of the shRNAmiR can be the sequence that is fully or partially complementary with the guide strand sequence. In some embodiments, the passenger strand is about 15 to about 25 nucleotides in length, including but not limited to about 15 to about 25 nucleotides in length, including but not limited to about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, and about 25 nucleotides long. In some of these embodiments, the passenger strand is about 22 nucleotides in length. In some of these embodiments, the passenger strand is about 21 nucleotides in length. In some embodiments, the passenger strand is shorter than the guide strand. The passenger strand can be at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, at least about 98%, at least about 99% or 100% complementary to the guide strand sequence. The passenger strand can comprise 1, 2, 3, 4, 5, or more mismatching nucleotides with the guide strand. In certain embodiments, however, the guide:passenger strand duplex does not comprise any mismatching nucleotides. In general, guide/passenger strand sequences should be selected that do not form any secondary structures within themselves. Further, the use of guide/passenger strand sequences that target sites within an mRNA that comprise single-nucleotide polymorphisms should be avoided. Guide/passenger strand sequences that are specific for the target mRNA are preferred to avoid any off-target effects (i.e., reduction in expression of non-target mRNAs). [0501] In order to aid in the selection of suitable shRNAmiR guide/passenger strands, or sequences for other shRNAmiR domains, any program known in the art that models the predicted secondary structure of an RNA molecule can be used, including but not limited to Mfold, RNAfold, and UNAFold. Any program known in the art that can predict the efficiency of a shRNA or miRNA guide/passenger sequence to target a particular mRNA can be used to select suitable guide/passenger strand sequences, including but not limited to those disclosed in Agarwal et al. (2015) eLife 4:e05005; and Knott et al. (2014) Mol Cell 56(6):796-807, each of which is incorporated herein in its entirety. shRNAmiR or shRNA Target Proteins [0502] The genetically-modified immune cells of the presently disclosed compositions and methods can comprise and express a pri-shRNAmiR or an shRNA that reduces the expression of any endogenous protein. Non-limiting examples of endogenous proteins whose expression can be reduced with a shRNAmiR or an shRNA include beta-2 microglobulin (B2M), TRAC, TRBC1, TRBC2, CIITA, or CD70. Non-limiting examples of endogenous proteins whose expression can be reduced with a shRNAmiR or an shRNA further include HLA-A, HLA-B, HLA-C, MICA, MICB, ULBP, PRV (PRV1; CD177), NKp30, NKp44, NKp46, HLA-DP, HLA- DQ, HLA-DR, TCRa (TCRα), TCRb (TCRβ), CD3e (CD3ε), CD3γ, CD3d (CD3δ), CD3z (CD3ζ), TET2, TET1, PD1, TIGIT, TIM3, LAG3, CTLA4, CD39, VISTA, NRA1, NRA2, NRA3, TOX1, TOX2, DGK, FAS, EOMES, PTPN2, PP2A, TGFBR1, TGFBR2, DNMT3A or DNMT3B. A. Beta-2 Microglobulin [0503] In some embodiments, the endogenous protein with reduced expression levels as the result of the expression of a shRNAmiR molecule or an shRNA molecule is B2M. B2M is a component of the major histocompatibility complex (MHC) class I molecule, which will not assemble on the cell surface without B2M present. MHC class I molecules are comprised of al, a2, and a3 proteins, in addition to B2M. Within MHC class I molecules, the B2M protein is situated beside the a3 protein and below the al protein on the cell surface. B2M lacks a transmembrane region and is necessary for the stability of the peptide-binding groove of MHC class I molecules. [0504] The shRNAmiR molecule or the shRNA molecule may target any region of a B2M mRNA. Representative B2M mRNA and protein sequences are known in the art. A non-limiting example of a B2M mRNA sequence is NCBI Acc. No. NM_004048.3 and a B2M protein sequence is NCBI Acc. No. NP_004039.1. [0505] In some of those embodiments wherein the expression of B2M is reduced by a shRNAmiR or an shRNA, the cell surface expression of B2M is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a B2M-targeted shRNAmiR or shRNA). Given that B2M is necessary for the assembly of the MHC class I molecule on the cell surface, cells with reduced expression of B2M also exhibit a reduction in MHC class I molecules on the cell surface. In some of these embodiments, the expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a B2M-targeted shRNAmiR or shRNA). [0506] shRNAmiR molecules that target B2M may comprise any passenger and corresponding guide sequence that is complementary (fully or partially) to a sequence within the B2M gene. In some embodiments, the passenger and guide sequence of the shRNAmiR comprise the sequences set forth as SEQ ID NO:166 and SEQ ID NO:167, respectively. [0507] The B2M-targeted pri-shRNAmiR may comprise a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more sequence identity to the nucleic acid sequence set forth in SEQ ID NO:168. In particular embodiments, the pri-shRNAmiR comprises the sequence set forth in SEQ ID NO:168. In some embodiments, the pri-shRNAmiR comprises the sequence set forth in SEQ ID NO:168. The B2M-targeted pre-shRNAmiR may comprise a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more sequence identity to the nucleic acid sequence set forth in SEQ ID NO:168. In particular embodiments, the pre-shRNAmiR comprises the sequence set forth in SEQ ID NO:168. [0508] shRNA molecules that target B2M may comprise any passenger and corresponding miRNA sequence that is complementary (fully or partially) to a sequence within the B2M gene. In some embodiments, the passenger and miRNA sequence of the shRNA molecules comprise the sequences set forth as SEQ ID NO:185 and SEQ ID NO:187, respectively. [0509] The B2M-targeted shRNA may comprise a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more sequence identity to the nucleic acid sequence set forth in SEQ ID NO:190. In particular embodiments, the shRNA comprises the sequence set forth in SEQ ID NO:190. In some embodiments, the shRNA comprises the sequence set forth in SEQ ID NO:190. The B2M-targeted shRNA may comprise a sequence having at least 50%, at least 55%, at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or more sequence identity to the nucleic acid sequence set forth in SEQ ID NO:190. In particular embodiments, the shRNA comprises the sequence set forth in SEQ ID NO:190. [0510] Cells with reduced levels of B2M and MHC class I molecules can exhibit reduced allogenicity compared to a control cell (e.g., a cell not expressing a B2M-targeted shRNAmiR or an shRNA). As used herein, the term “allogenicity” refers to the ability of a cell to be recognized and acted upon by the immune system as “other” or not autologous. Allogenicity can be measured using any method known in the art, including those methods described elsewhere herein wherein the percentage of living cells were quantitated after incubation with primed alloantigen-specific CTLs or NK cells. B. TRAC [0511] In some embodiments, the endogenous protein with reduced expression levels as the result of the expression of a shRNAmiR molecule or an shRNA molecule is TRAC. TRAC is a component of the major histocompatibility complex (MHC) class I molecule, which will not assemble on the cell surface without TRAC present. MHC class I molecules are comprised of al, a2, and a3 proteins, in addition to TRAC. Within MHC class I molecules, the TRAC protein is situated beside the a3 protein and below the al protein on the cell surface. TRAC lacks a transmembrane region and is necessary for the stability of the peptide-binding groove of MHC class I molecules. [0512] The shRNAmiR molecule or the shRNA molecule may target any region of a TRAC mRNA. Representative TRAC mRNA and protein sequences are known in the art. A non- limiting example of a TRAC mRNA sequence is NCBI Acc. No. X02592.1 and a TRAC protein sequence is NCBI Acc. No. NP_ P01848.2. [0513] In some of those embodiments wherein the expression of TRAC is reduced by a shRNAmiR or an shRNA, the cell surface expression of TRAC is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a TRAC-targeted shRNAmiR or shRNA). Given that TRAC is necessary for the assembly of the MHC class I molecule on the cell surface, cells with reduced expression of TRAC also exhibit a reduction in MHC class I molecules on the cell surface. In some of these embodiments, the expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a TRAC-targeted shRNAmiR or shRNA). [0514] shRNAmiR molecules or shRNA molecules that target TRAC may comprise any passenger and corresponding guide sequence that is complementary (fully or partially) to a sequence within the TRAC gene. [0515] Cells with reduced levels of TRAC and MHC class I molecules can exhibit reduced allogenicity compared to a control cell (e.g., a cell not expressing a TRAC-targeted shRNAmiR or shRNA). Allogenicity can be measured using any method known in the art, including those methods described elsewhere herein wherein the percentage of living cells were quantitated after incubation with primed alloantigen-specific CTLs or NK cells. C. TRBC1 [0516] In some embodiments, the endogenous protein with reduced expression levels as the result of the expression of a shRNAmiR molecule or an shRNA molecule is TRBC1. TRBC1 is a component of the major histocompatibility complex (MHC) class I molecule, which will not assemble on the cell surface without TRBC1 present. MHC class I molecules are comprised of al, a2, and a3 proteins, in addition to TRBC1. Within MHC class I molecules, the TRBC1 protein is situated beside the a3 protein and below the al protein on the cell surface. TRBC1 lacks a transmembrane region and is necessary for the stability of the peptide-binding groove of MHC class I molecules. [0517] The shRNAmiR molecule or the shRNA molecule may target any region of a TRBC1 mRNA. Representative TRBC1 mRNA and protein sequences are known in the art. A non- limiting example of a TRBC1 mRNA sequence is NCBI Acc. No. X00437.1 and a TRBC1 protein sequence is NCBI Acc. No. P01850.4. [0518] In some of those embodiments wherein the expression of TRBC1 is reduced by a shRNAmiR or an shRNA, the cell surface expression of TRBC1 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a TRBC1-targeted shRNAmiR or shRNA). Given that TRBC1 is necessary for the assembly of the MHC class I molecule on the cell surface, cells with reduced expression of TRBC1 also exhibit a reduction in MHC class I molecules on the cell surface. In some of these embodiments, the expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a TRBC1- targeted shRNAmiR or shRNA). [0519] shRNAmiR molecules or shRNA molecules that target TRBC1 may comprise any passenger and corresponding guide sequence that is complementary (fully or partially) to a sequence within the TRBC1 gene. [0520] Cells with reduced levels of TRBC1 and MHC class I molecules can exhibit reduced allogenicity compared to a control cell (e.g., a cell not expressing a TRBC1-targeted shRNAmiR or shRNA). Allogenicity can be measured using any method known in the art, including those methods described elsewhere herein wherein the percentage of living cells were quantitated after incubation with primed alloantigen-specific CTLs or NK cells. D. TRBC2 [0521] In some embodiments, the endogenous protein with reduced expression levels as the result of the expression of a shRNAmiR molecule or an shRNA molecule is TRBC2. TRBC2 is a component of the major histocompatibility complex (MHC) class I molecule, which will not assemble on the cell surface without TRBC2 present. MHC class I molecules are comprised of a1, a2, and a3 proteins, in addition to TRBC2. Within MHC class I molecules, the TRBC2 protein is situated beside the a3 protein and below the al protein on the cell surface. TRBC2 lacks a transmembrane region and is necessary for the stability of the peptide-binding groove of MHC class I molecules. [0522] The shRNAmiR molecule or the shRNA molecule may target any region of a TRBC2 mRNA. Representative TRBC2 mRNA and protein sequences are known in the art. A non- limiting example of a TRBC2 mRNA sequence is Genbank ID No: M12888.1 and a TRBC2 protein sequence is Uniprot ID No: A0A5B9. [0523] In some of those embodiments wherein the expression of TRBC2 is reduced by a shRNAmiR or an shRNA, the cell surface expression of TRBC2 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a TRBC2-targeted shRNAmiR or shRNA). Given that TRBC2 is necessary for the assembly of the MHC class I molecule on the cell surface, cells with reduced expression of TRBC2 also exhibit a reduction in MHC class I molecules on the cell surface. In some of these embodiments, the expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a TRBC2- targeted shRNAmiR or shRNA). [0524] The shRNAmiR molecules or the shRNA molecules that target TRBC2 may comprise any passenger and corresponding guide sequence that is complementary (fully or partially) to a sequence within the TRBC2 gene. [0525] Cells with reduced levels of TRBC2 and MHC class I molecules can exhibit reduced allogenicity compared to a control cell (e.g., a cell not expressing a TRBC2-targeted shRNAmiR or shRNA). Allogenicity can be measured using any method known in the art, including those methods described elsewhere herein wherein the percentage of living cells were quantitated after incubation with primed alloantigen-specific CTLs or NK cells. E. CIITA [0526] In some embodiments, the endogenous protein with reduced expression levels as the result of the expression of a shRNAmiR molecule or an shRNA molecule is CIITA. CIITA is a component of the major histocompatibility complex (MHC) class I molecule, which will not assemble on the cell surface without CIITA present. MHC class I molecules are comprised of a1, a2, and a3 proteins, in addition to CIITA. Within MHC class I molecules, the CIITA protein is situated beside the a3 protein and below the al protein on the cell surface. CIITA lacks a transmembrane region and is necessary for the stability of the peptide-binding groove of MHC class I molecules. [0527] The shRNAmiR molecule or the shRNA molecule may target any region of a CIITA mRNA. Representative CIITA mRNA and protein sequences are known in the art. A non- limiting example of a CIITA mRNA sequence is NCBI Acc. No. X74301.1 and a CIITA protein sequence is NCBI Acc. No. P33076.3. [0528] In some of those embodiments wherein the expression of CIITA is reduced by a shRNAmiR or an shRNA, the cell surface expression of CIITA is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a CIITA-targeted shRNAmiR or shRNA). Given that CIITA is necessary for the assembly of the MHC class I molecule on the cell surface, cells with reduced expression of CIITA also exhibit a reduction in MHC class I molecules on the cell surface. In some of these embodiments, the expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a CIITA-targeted shRNAmiR or shRNA). [0529] The shRNAmiR molecules or the shRNA molecules that target CIITA may comprise any passenger and corresponding guide sequence that is complementary (fully or partially) to a sequence within the CIITA gene. [0530] Cells with reduced levels of CIITA and MHC class I molecules can exhibit reduced allogenicity compared to a control cell (e.g., a cell not expressing a CIITA-targeted shRNAmiR or shRNA). Allogenicity can be measured using any method known in the art, including those methods described elsewhere herein wherein the percentage of living cells were quantitated after incubation with primed alloantigen-specific CTLs or NK cells. F. CD70 [0531] In some embodiments, the endogenous protein with reduced expression levels as the result of the expression of a shRNAmiR molecule or an shRNA molecule is CD70. CD70 is a component of the major histocompatibility complex (MHC) class I molecule, which will not assemble on the cell surface without CD70 present. MHC class I molecules are comprised of al, a2, and a3 proteins, in addition to CD70. Within MHC class I molecules, the CD70 protein is situated beside the a3 protein and below the al protein on the cell surface. CD70 lacks a transmembrane region and is necessary for the stability of the peptide-binding groove of MHC class I molecules. [0532] The shRNAmiR molecule or the shRNA molecule may target any region of a CD70 mRNA. Representative CD70 mRNA and protein sequences are known in the art. A non-limiting example of a CD70 mRNA sequence is NCBI Acc. No. BT007211.1, L08096.1, or S69339.1 and a CD70 protein sequence is NCBI Acc. No. AAP35875.1, AAA36175.1, or AAB30121.1. [0533] In some of those embodiments wherein the expression of CD70 is reduced by a shRNAmiR or an shRNA, the cell surface expression of CD70 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a CD70-targeted shRNAmiR or shRNA). Given that CD70 is necessary for the assembly of the MHC class I molecule on the cell surface, cells with reduced expression of CD70 also exhibit a reduction in MHC class I molecules on the cell surface. In some of these embodiments, the expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a CD70-targeted shRNAmiR or shRNA). [0534] The shRNAmiR molecules or the shRNA molecules that target CD70 may comprise any passenger and corresponding guide sequence that is complementary (fully or partially) to a sequence within the CD70 gene. [0535] Cells with reduced levels of CD70 and MHC class I molecules can exhibit reduced allogenicity compared to a control cell (e.g., a cell not expressing a CD70-targeted shRNAmiR or shRNA). Allogenicity can be measured using any method known in the art, including those methods described elsewhere herein wherein the percentage of living cells were quantitated after incubation with primed alloantigen-specific CTLs or NK cells. T cell receptor (TCR) fusion proteins (TFPs) [0536] The present disclosure encompasses recombinant nucleic acid constructs encoding TFPs, wherein the TFP comprises a binding domain, e.g., an antibody or antibody fragment, a ligand, or a ligand binding protein, wherein the sequence of the binding domain is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof. The antibody or antibody fragment can comprise an antigen binding domain selected from a group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, an anti-79b binding domain, , an anti-PMSA binding domain, an anti-MUC16 binding domain, an anti-CD22 binding domain, an anti-PD-L1 binding domain, an anti BAFF receptor binding domain, an anti-Nectin-4 binding domain, an anti-TROP-2 binding domain, an anti-GPC3 binding domain, and anti-ROR-1 binding domain. For example, the present disclosure encompasses recombinant nucleic acid constructs encoding TFPs, wherein the TFP comprises an antibody fragment that binds specifically to CD19, e.g., human CD19, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof. For another example, the present disclosure encompasses recombinant nucleic acid constructs encoding TFPs, wherein the TFP comprises an antibody fragment that binds specifically to mesothelin, e.g., human mesothelin, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof. The present disclosure encompasses recombinant DNA constructs encoding TFPs, wherein the TFP comprises an antibody fragment that binds specifically to MUC16, e.g., human MUC16, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof. The present disclosure encompasses recombinant DNA constructs encoding TFPs, wherein the TFP comprises an antibody fragment that binds specifically to CD20, e.g., human CD20, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof. The present disclosure encompasses recombinant DNA constructs encoding TFPs, wherein the TFP comprises an antibody fragment that binds specifically to CD70, e.g., human CD70, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof. The present disclosure encompasses recombinant DNA constructs encoding TFPs, wherein the TFP comprises an antibody fragment that binds specifically to CD79B, e.g., human CD79B, wherein the sequence of the antibody fragment is contiguous with and in the same reading frame as a nucleic acid sequence encoding a TCR subunit or portion thereof. The TFPs provided herein are able to associate with one or more endogenous (or alternatively, one or more exogenous, or a combination of endogenous and exogenous) TCR subunits in order to form a functional TCR complex. [0537] In one aspect, the TFP of the present disclosure comprises a target-specific binding element otherwise referred to as an antigen binding domain. The choice of moiety depends upon the type and number of target antigen that define the surface of a target cell. For example, the antigen binding domain may be chosen to recognize a target antigen that acts as a cell surface marker on target cells associated with a particular disease state. Thus, examples of cell surface markers that may act as target antigens for the antigen binding domain in a TFP of the present disclosure include those associated with viral, bacterial and parasitic infections; autoimmune diseases; and cancerous diseases (e.g., malignant diseases). [0538] In one aspect, the TFP-mediated T cell response can be directed to an antigen of interest by way of engineering an antigen-binding domain into the TFP that specifically binds a desired antigen. [0539] The antigen binding domain can be any domain that binds to the antigen including but not limited to a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a human antibody, a humanized antibody, and a functional fragment thereof, including but not limited to a single-domain antibody such as a heavy chain variable domain (VH), a light chain variable domain (VL) and a variable domain (VHH) of a camelid derived nanobody, and to an alternative scaffold known in the art to function as antigen binding domain, such as a recombinant fibronectin domain, anticalin, DARPIN and the like. Likewise, a natural or synthetic ligand specifically recognizing and binding the target antigen can be used as antigen binding domain for the TFP. In some instances, it is beneficial for the antigen binding domain to be derived from the same species in which the TFP will ultimately be used in. For example, for use in humans, it may be beneficial for the antigen binding domain of the TFP to comprise human or humanized residues for the antigen binding domain of an antibody or antibody fragment. [0540] Thus, in one aspect, the antigen-binding domain comprises a humanized or human antibody or an antibody fragment, or a murine antibody or antibody fragment. In one embodiment, the humanized or human anti-TAA binding domain comprises one or more (e.g., all three) light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) of a humanized or human anti-TAA binding domain described herein, and/or one or more (e.g., all three) heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) of a humanized or human anti-CD19 binding domain described herein, e.g., a humanized or human anti-TAA binding domain comprising one or more, e.g., all three, LC CDRs and one or more, e.g., all three, HC CDRs. In one embodiment, the humanized or human anti-CD19 binding domain comprises one or more (e.g., all three) heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) of a humanized or human anti-TAA binding domain described herein, e.g., the humanized or human anti-TAA binding domain has two variable heavy chain regions, each comprising a HC CDR1, a HC CDR2 and a HC CDR3 described herein. In one embodiment, the humanized or human anti-TAA binding domain comprises a humanized or human light chain variable region described herein and/or a humanized or human heavy chain variable region described herein. In one embodiment, the humanized or human anti-TAA binding domain comprises a humanized heavy chain variable region described herein, e.g., at least two humanized or human heavy chain variable regions described herein. In one embodiment, the anti-TAA binding domain is a scFv comprising a light chain and a heavy chain of an amino acid sequence provided herein. In an embodiment, the anti-TAA binding domain (e.g., a scFv) comprises: a light chain variable region comprising an amino acid sequence having at least one, two or three modifications (e.g., substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions) of an amino acid sequence of a light chain variable region provided herein, or a sequence with 95-99% identity with an amino acid sequence provided herein; and/or a heavy chain variable region comprising an amino acid sequence having at least one, two or three modifications (e.g., substitutions) but not more than 30, 20 or 10 modifications (e.g., substitutions) of an amino acid sequence of a heavy chain variable region provided herein, or a sequence with 95-99% identity to an amino acid sequence provided herein. In one embodiment, the humanized or human anti-TAA binding domain is a scFv, and a light chain variable region comprising an amino acid sequence described herein, is attached to a heavy chain variable region comprising an amino acid sequence described herein, via a linker, e.g., a linker described herein. In one embodiment, the humanized anti-TAA binding domain includes a (Gly4-Ser)n linker, wherein n is 1, 2, 3, 4, 5, or 6, preferably 3 or 4. The light chain variable region and heavy chain variable region of a scFv can be, e.g., in any of the following orientations: light chain variable region-linker-heavy chain variable region or heavy chain variable region-linker-light chain variable region. In some instances, the linker sequence comprises a long linker (LL) sequence. In some instances, the long linker sequence comprises (G4S)n, wherein n=2 to 4. In some instances, the linker sequence comprises a short linker (SL) sequence. In some instances, the short linker sequence comprises (G4S)n, wherein n=1 to 3. [0541] In some embodiments, the antigen-binding domain comprises an anti-CD19 humanized or human antibody or an antibody fragment, or a murine antibody or antibody fragment having a light chain CDR1 of SEQ ID NO:73, a CDR2 of SEQ ID NO:75, and a CDR3 of SEQ ID NO:77 and a heavy chain CDR1 of SEQ ID NO:79, a CDR2 of SEQ ID NO:81, and a CDR3 of SEQ ID NO:83. In some embodiments, the anti-CD19 antibody is a murine scFv. In some embodiments, the anti-CD-19 antibody comprises a VL of SEQ ID NO:85 and a VH of SEQ ID NO:87 [0542] In some embodiments, the antigen-binding domain comprises an anti-mesothelin humanized or human single domain antibody or an antibody fragment having a CDR1 of SEQ ID NO:60, a CDR2 of SEQ ID NO:61, and a CDR3 of SEQ ID NO:62 or a CDR1 of SEQ ID NO:63, a CDR2 of SEQ ID NO:64, and a CDR3 of SEQ ID NO:65. In some embodiments, the anti-mesothelin antibody has a variable domain of SEQ ID NO:69, or SEQ ID NO:70. [0543] In some embodiments, the antigen-binding domain comprises an anti-CD70 humanized or human single domain antibody or an antibody fragment having a CDR1 of SEQ ID NO:88, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:90, or a CDR1 of SEQ ID NO:92, a CDR2 of SEQ ID NO:93, and a CDR3 of SEQ ID NO:94, or a CDR1 of SEQ ID NO:96, a CDR2 of SEQ ID NO:97, and a CDR3 of SEQ ID NO:98, or a CDR1 of SEQ ID NO:100, a CDR2 of SEQ ID NO:101, and a CDR3 of SEQ ID NO:102, or a CDR1 of SEQ ID NO:104, a CDR2 of SEQ ID NO:105, and a CDR3 of SEQ ID NO:106, or a CDR1 of SEQ ID NO:108, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:110, or a CDR1 of SEQ ID NO:112, a CDR2 of SEQ ID NO:113, and a CDR3 of SEQ ID NO:114, or a CDR1 of SEQ ID NO:116, a CDR2 of SEQ ID NO:117, and a CDR3 of SEQ ID NO:118, or a CDR1 of SEQ ID NO:120, a CDR2 of SEQ ID NO:121, and a CDR3 of SEQ ID NO:122. [0544] In some embodiments, the antigen-binding domain comprises an anti-CD70 single chain Fv (scFv) or an antibody fragment thereof. The anti-CD70 scFv or antibody fragment thereof can comprise a heavy chain complementary determining region 1 (CDRH1) having a sequence of SEQ ID NO:361, a CDRH2 having a sequence of SEQ ID NO:362, and a CDRH3 having a sequence of SEQ ID NOs: 363. The anti-CD70 scFv or antibody fragment thereof can comprise a light chain complementary determining region 1 (CDRL1) having a sequence of SEQ ID NO:365 , a CDRL2 having a sequence of SEQ ID NO:366, and a CDRL3 having a sequence of SEQ ID NO:367. The anti-CD70 scFv or antibody fragment thereof can comprise a heavy chain variable (VH) domain having at least 70%, 75%, 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:364. The anti-CD70 scFv or antibody fragment thereof can comprise a light chain variable (VL) domain having at least 70%, 75%, 80%, 85%, 90%, 95%, or 100% sequence identity to SEQ ID NO:368. [0545] In some aspects, a non-human antibody is humanized, where specific sequences or regions of the antibody are modified to increase similarity to an antibody naturally produced in a human or fragment thereof. In one aspect, the antigen binding domain is humanized. [0546] A humanized antibody can be produced using a variety of techniques known in the art, including but not limited to, CDR-grafting (see, e.g., European Patent No. EP 239,400; International Publication No. WO 91/09967; and U.S. Pat. Nos.5,225,539, 5,530,101, and 5,585,089, each of which is incorporated herein in its entirety by reference), veneering or resurfacing (see, e.g., European Patent Nos. EP 592,106 and EP 519,596; Padlan, 1991, Molecular Immunology, 28(4/5):489-498; Studnicka et al., 1994, Protein Engineering, 7(6):805- 814; and Roguska et al., 1994, PNAS, 91:969-973, each of which is incorporated herein by its entirety by reference), chain shuffling (see, e.g., U.S. Pat. No.5,565,332, which is incorporated herein in its entirety by reference), and techniques disclosed in, e.g., U.S. Patent Application Publication No. US2005/0042664, U.S. Patent Application Publication No. US2005/0048617, U.S. Pat. No.6,407,213, U.S. Pat. No.5,766,886, International Publication No. WO 9317105, Tan et al., J. Immunol., 169:1119-25 (2002), Caldas et al., Protein Eng., 13(5):353-60 (2000), Morea et al., Methods, 20(3):267-79 (2000), Baca et al., J. Biol. Chem., 272(16):10678-84 (1997), Roguska et al., Protein Eng., 9(10):895-904 (1996), Couto et al., Cancer Res., 55 (23 Supp):5973s-5977s (1995), Couto et al., Cancer Res., 55(8):1717-22 (1995), Sandhu J S, Gene, 150(2):409-10 (1994), and Pedersen et al., J. Mol. Biol., 235(3):959-73 (1994), each of which is incorporated herein in its entirety by reference. Often, framework residues in the framework regions will be substituted with the corresponding residue from the CDR donor antibody to alter, for example improve, antigen binding. These framework substitutions are identified by methods well-known in the art, e.g., by modeling of the interactions of the CDR and framework residues to identify framework residues important for antigen binding and sequence comparison to identify unusual framework residues at particular positions (see, e.g., Queen et al., U.S. Pat. No. 5,585,089; and Riechmann et al., 1988, Nature, 332:323, which are incorporated herein by reference in their entireties.) [0547] A humanized antibody or antibody fragment has one or more amino acid residues remaining in it from a source which is nonhuman. These nonhuman amino acid residues are often referred to as “import” residues, which are typically taken from an “import” variable domain. As provided herein, humanized antibodies or antibody fragments comprise one or more CDRs from nonhuman immunoglobulin molecules and framework regions wherein the amino acid residues comprising the framework are derived completely or mostly from human germline. Multiple techniques for humanization of antibodies or antibody fragments are well-known in the art and can essentially be performed following the method of Winter and co-workers (Jones et al., Nature, 321:522-525 (1986); Riechmann et al., Nature, 332:323-327 (1988); Verhoeyen et al., Science, 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody, i.e., CDR-grafting (EP 239,400; PCT Publication No. WO 91/09967; and U.S. Pat. Nos.4,816,567; 6,331,415; 5,225,539; 5,530,101; 5,585,089; 6,548,640, the contents of which are incorporated herein by reference in their entirety). In such humanized antibodies and antibody fragments, substantially less than an intact human variable domain has been substituted by the corresponding sequence from a nonhuman species. Humanized antibodies are often human antibodies in which some CDR residues and possibly some framework (FR) residues are substituted by residues from analogous sites in rodent antibodies. Humanization of antibodies and antibody fragments can also be achieved by veneering or resurfacing (EP 592,106; EP 519,596; Padlan, 1991, Molecular Immunology, 28(4/5):489-498; Studnicka et al., Protein Engineering, 7(6):805-814 (1994); and Roguska et al., Proc. Natl. Acad. Sci. USA, 91:969-973 (1994)) or chain shuffling (U.S. Pat. No.5,565,332), the contents of which are incorporated herein by reference in their entirety. [0548] The choice of human variable domains, both light and heavy, to be used in making the humanized antibodies is to reduce antigenicity. According to the so-called “best-fit” method, the sequence of the variable domain of a rodent antibody is screened against the entire library of known human variable-domain sequences. The human sequence which is closest to that of the rodent is then accepted as the human framework (FR) for the humanized antibody (Sims et al., J. Immunol., 151:2296 (1993); Chothia et al., J. Mol. Biol., 196:901 (1987), the contents of which are incorporated herein by reference herein in their entirety). Another method uses a particular framework derived from the consensus sequence of all human antibodies of a particular subgroup of light or heavy chains. The same framework may be used for several different humanized antibodies (see, e.g., Nicholson et al., Mol. Immun.34 (16-17): 1157-1165 (1997); Carter et al., Proc. Natl. Acad. Sci. USA, 89:4285 (1992); Presta et al., J. Immunol., 151:2623 (1993), the contents of which are incorporated herein by reference herein in their entirety). In some embodiments, the framework region, e.g., all four framework regions, of the heavy chain variable region are derived from a VH4-4-59 germline sequence. In one embodiment, the framework region can comprise, one, two, three, four or five modifications, e.g., substitutions, e.g., from the amino acid at the corresponding murine sequence. In one embodiment, the framework region, e.g., all four framework regions of the light chain variable region are derived from a VK3-1.25 germline sequence. In one embodiment, the framework region can comprise, one, two, three, four or five modifications, e.g., substitutions, e.g., from the amino acid at the corresponding murine sequence. [0549] In some aspects, the portion of a TFP composition of the present disclosure that comprises an antibody fragment is humanized with retention of high affinity for the target antigen and other favorable biological properties. According to one aspect of the present disclosure, humanized antibodies and antibody fragments are prepared by a process of analysis of the parental sequences and various conceptual humanized products using three-dimensional models of the parental and humanized sequences. Three-dimensional immunoglobulin models are commonly available and are familiar to those skilled in the art. Computer programs are available which illustrate and display probable three-dimensional conformational structures of selected candidate immunoglobulin sequences. Inspection of these displays permits analysis of the likely role of the residues in the functioning of the candidate immunoglobulin sequence, e.g., the analysis of residues that influence the ability of the candidate immunoglobulin to bind the target antigen. In this way, FR residues can be selected and combined from the recipient and import sequences so that the desired antibody or antibody fragment characteristic, such as increased affinity for the target antigen, is achieved. In general, the CDR residues are directly and most substantially involved in influencing antigen binding. [0550] A humanized antibody or antibody fragment may retain a similar antigenic specificity as the original antibody, e.g., in the present disclosure, the ability to bind human a tumor associated antigen (TAA). In some embodiments, a humanized antibody or antibody fragment may have improved affinity and/or specificity of binding to, e.g., human CD19, human BCMA, or another tumor associated antigen. [0551] In one aspect, the binding domain is characterized by particular functional features or properties of an antibody or antibody fragment. In certain aspects, the scFv is contiguous with and in the same reading frame as a leader sequence. [0552] In one aspect, the anti-tumor-associated antigen binding domain is a fragment, e.g., a single chain variable fragment (scFv). In one aspect, the anti-TAA binding domain is a Fv, a Fab, a (Fab’)2, or a bi-functional (e.g. bi-specific) hybrid antibody (e.g., Lanzavecchia et al., Eur. J. Immunol.17, 105 (1987)). In one aspect, the antibodies and fragments thereof of the present disclosure binds a CD19 protein with wild-type or enhanced affinity. In another aspect, the anti- TAA binding domain comprises a single domain antibody (sdAb or VHH). [0553] Also provided herein are methods for obtaining an antibody antigen binding domain specific for a target antigen (e.g., CD19, BCMA, MSLN, CD70, or any target antigen described elsewhere herein for targets of fusion moiety binding domains), the method comprising providing by way of addition, deletion, substitution or insertion of one or more amino acids in the amino acid sequence of a VH domain set out herein a VH domain which is an amino acid sequence variant of the VH domain, optionally combining the VH domain thus provided with one or more VL domains, and testing the VH domain or VH/VL combination or combinations to identify a specific binding member or an antibody antigen binding domain specific for a target antigen of interest (e.g., MSLN, CD79B, etc.) and optionally with one or more desired properties. [0554] In some instances, VH domains and scFvs can be prepared according to method known in the art (see, for example, Bird et al., (1988) Science 242:423-426 and Huston et al., (1988) Proc. Natl. Acad. Sci. USA 85:5879-5883). scFv molecules can be produced by linking VH and VL regions together using flexible polypeptide linkers. The scFv molecules comprise a linker (e.g., a Ser-Gly linker) with an optimized length and/or amino acid composition. The linker length can greatly affect how the variable regions of a scFv fold and interact. In fact, if a short polypeptide linker is employed (e.g., between 5-10 amino acids) intra-chain folding is prevented. Inter-chain folding is also required to bring the two variable regions together to form a functional epitope binding site. In some instances, the linker sequence comprises a linker sequence. In some instances, the long linker sequence comprises (G4S)n, wherein n=2 to 4. In some instances, the linker sequence comprises (G4S)n, wherein n=1 to 3. For examples of linker orientation and size see, e.g., Hollinger et al., 1993 Proc Natl Acad. Sci. U.S.A.90:6444-6448, U.S. Patent Application Publication Nos.2005/0100543, 2005/0175606, 2007/0014794, and PCT publication Nos. WO2006/020258 and WO2007/024715, each of which is incorporated herein by reference. [0555] An scFv can comprise a linker of about 10, 11, 12, 13, 14, 15 or greater than 15 residues between its VL and VH regions. The linker sequence may comprise any naturally occurring amino acid. In some embodiments, the linker sequence comprises amino acids glycine and serine. In another embodiment, the linker sequence comprises sets of glycine and serine repeats such as (Gly4Ser)n, where n is a positive integer equal to or greater than 1. In one embodiment, the linker can be (Gly4Ser)4 or (Gly4Ser)3. Variation in the linker length may retain or enhance activity, giving rise to superior efficacy in activity studies. In some instances, the linker sequence comprises (G4S)n, wherein n=2 to 4. In some instances, the linker sequence comprises (G4S)n, wherein n=1 to 3. In some embodiments, the linker sequence comprises GGSGGSGGSGGS (SEQ ID NO:369). Stability and Mutations [0556] The stability of a tumor associated antigen binding domain, e.g., scFv molecules (e.g., soluble scFv) can be evaluated in reference to the biophysical properties (e.g., thermal stability) of a conventional control scFv molecule or a full-length antibody. In one embodiment, the humanized or human scFv has a thermal stability that is greater than about 0.1, about 0.25, about 0.5, about 0.75, about 1, about 1.25, about 1.5, about 1.75, about 2, about 2.5, about 3, about 3.5, about 4, about 4.5, about 5, about 5.5, about 6, about 6.5, about 7, about 7.5, about 8, about 8.5, about 9, about 9.5, about 10 degrees, about 11 degrees, about 12 degrees, about 13 degrees, about 14 degrees, or about 15 degrees Celsius than a parent scFv in the described assays. [0557] The improved thermal stability of the anti-TAA binding domain, e.g., scFv is subsequently conferred to the entire TAA-TFP construct, leading to improved therapeutic properties of the anti-TAA TFP construct. The thermal stability of the binding domain, e.g., scFv or sdAb, can be improved by at least about 2 °C or 3 °C as compared to a conventional antibody. In one embodiment, the binding domain, has a 1 °C improved thermal stability as compared to a conventional antibody. In another embodiment, the binding domain, has a 2 °C improved thermal stability as compared to a conventional antibody. In another embodiment, the scFv has a 4 °C, 5 °C, 6 °C, 7 °C, 8 °C, 9 °C, 10 °C, 11 °C, 12 °C, 13 °C, 14 °C, or 15 °C improved thermal stability as compared to a conventional antibody. Comparisons can be made, for example, between the scFv molecules disclosed herein and scFv molecules or Fab fragments of an antibody from which the scFv VH and VL were derived. Thermal stability can be measured using methods known in the art. For example, in one embodiment, TM can be measured. Methods for measuring TM and other methods of determining protein stability are described in more detail below. [0558] Mutations in antibody sequences (arising through humanization or direct mutagenesis of the soluble scFv) alter the stability of the antibody or fragment thereof and improve the overall stability of the antibody and the TFP construct. Stability of the humanized antibody or fragment thereof is compared against the murine antibody or fragment thereof using measurements such as TM, temperature denaturation and temperature aggregation. In one embodiment, the binding domain, e.g., a scFv or sdAb, comprises at least one mutation arising from the humanization process such that the mutated scFv confers improved stability to the anti-TAA TFP construct. In another embodiment, the anti-TAA binding domain, e.g., scFv or sdAb, comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 mutations arising from the humanization process such that the mutated scFv or sdAb confers improved stability to the TAA-TFP construct. [0559] In one aspect, the antigen binding domain of the TFP comprises an amino acid sequence that is homologous to an antigen binding domain amino acid sequence described herein, and the antigen binding domain retains the desired functional properties of the anti-tumor-associated antigen antibody fragments described herein. In one specific aspect, the TFP composition of the present disclosure comprises an antibody fragment. In a further aspect, that antibody fragment comprises a scFv. [0560] In various aspects, the antigen binding domain of the TFP is engineered by modifying one or more amino acids within one or both variable regions (e.g., VH and/or VL), for example within one or more CDR regions and/or within one or more framework regions. In one specific aspect, the TFP composition of the present disclosure comprises an antibody fragment. In a further aspect, that antibody fragment comprises a scFv. [0561] It will be understood by one of ordinary skill in the art that the antibody or antibody fragment of the present disclosure may further be modified such that they vary in amino acid sequence (e.g., from wild-type), but not in desired activity. For example, additional nucleotide substitutions leading to amino acid substitutions at “non-essential” amino acid residues may be made to the protein. For example, a nonessential amino acid residue in a molecule may be replaced with another amino acid residue from the same side chain family. In another embodiment, a string of amino acids can be replaced with a structurally similar string that differs in order and/or composition of side chain family members, e.g., a conservative substitution, in which an amino acid residue is replaced with an amino acid residue having a similar side chain, may be made. [0562] Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). [0563] Percent identity in the context of two or more nucleic acids or polypeptide sequences refers to two or more sequences that are the same. Two sequences are “substantially identical” if two sequences have a specified percentage of amino acid residues or nucleotides that are the same (e.g., 60% identity, optionally 70%, 71% , 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% identity over a specified region, or, when not specified, over the entire sequence), when compared and aligned for maximum correspondence over a comparison window, or designated region as measured using one of the following sequence comparison algorithms or by manual alignment and visual inspection. Optionally, the identity exists over a region that is at least about 50 nucleotides (or 10 amino acids) in length, or more preferably over a region that is 100 to 500 or 1000 or more nucleotides (or 20, 50, 200 or more amino acids) in length. [0564] For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters. Methods of alignment of sequences for comparison are well known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith and Waterman, (1970) Adv. Appl. Math.2:482c, by the homology alignment algorithm of Needleman and Wunsch, (1970) J. Mol. Biol.48:443, by the search for similarity method of Pearson and Lipman, (1988) Proc. Natl. Acad. Sci. USA 85:2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by manual alignment and visual inspection (see, e.g., Brent et al., (2003) Current Protocols in Molecular Biology). Two examples of algorithms that are suitable for determining percent sequence identity and sequence similarity are the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al., (1977) Nuc. Acids Res.25:3389-3402; and Altschul et al., (1990) J. Mol. Biol.215:403-410, respectively. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. [0565] In one aspect, the present disclosure contemplates modifications of the starting antibody or fragment (e.g., scFv) amino acid sequence that generate functionally equivalent molecules. For example, the VH or VL of a binding domain, e.g., scFv, comprised in the TFP can be modified to retain at least about 70%, 71%.72%.73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity of the starting VH or VL framework region of the anti-CD19 binding domain, e.g., scFv. The present disclosure contemplates modifications of the entire TFP construct, e.g., modifications in one or more amino acid sequences of the various domains of the TFP construct in order to generate functionally equivalent molecules. The TFP construct can be modified to retain at least about 70%, 71%.72%.73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% identity of the starting TFP construct. Extracellular domain [0566] The extracellular domain may be derived either from a natural or from a recombinant source. Where the source is natural, the domain may be derived from any protein, but in particular a membrane-bound or transmembrane protein. In one aspect the extracellular domain is capable of associating with the transmembrane domain. An extracellular domain of particular use in this present disclosure may include at least the extracellular region(s) of e.g., the alpha, beta or zeta chain of the T cell receptor, or CD3 epsilon, CD3 gamma, or CD3 delta, or in alternative embodiments, CD28, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134, CD137, or CD154. In some embodiments, the extracellular domain is a TCR extracellular domain. In some instances, the TCR extracellular domain comprises an extracellular domain or portion thereof of a protein selected from the group consisting of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, a CD3 delta TCR subunit, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0567] In some embodiments, the TCR extracellular domain comprises an extracellular domain or portion thereof of a TCR alpha chain, a TCR beta chain, a TCR delta chain, or a TCR gamma chain. In some embodiments, the TCR extracellular domain comprises the extracellular portion of a constant domain of a TCR alpha chain, a TCR beta chain, a TCR delta chain, or a TCR gamma chain. [0568] In some embodiments, the extracellular domain comprises, or comprises at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more consecutive amino acid residues of the extracellular domain of a TCR alpha chain, a TCR beta chain, a TCR delta chain, or a TCR gamma chain. In some embodiments, the extracellular domain comprises a sequence having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more sequence identity to a sequence encoding the extracellular domain of a TCR alpha chain, a TCR beta chain, a TCR delta chain, or a TCR gamma chain. In some embodiments, the extracellular domain comprises a sequence encoding the extracellular domain of a TCR alpha chain, a TCR beta chain, a TCR delta chain, or a TCR gamma chain having a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more amino acids at the N- or C-terminus or at both the N- and C-terminus. [0569] In some embodiments, the extracellular domain comprises, or comprises at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more consecutive amino acid residues of an extracellular portion of a constant domain or IgC domain of TCR alpha, a TCR beta, a TCR delta, or a TCR gamma. In some embodiments, the extracellular domain comprises a sequence having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more sequence identity to a sequence encoding an extracellular portion of a constant domain or IgC domain of TCR alpha, a TCR beta, a TCR delta, or a TCR gamma. In some embodiments, the extracellular domain comprises a sequence encoding an extracellular portion of a constant domain or IgC domain of TCR alpha, TCR beta, TCR delta, or TCR gamma having a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more amino acids at the N- or C-terminus or at both the N- and C-terminus. [0570] In some embodiments, the extracellular domain comprises, or comprises at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100 or more consecutive amino acid residues of the extracellular domain of a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit. In some embodiments, the extracellular domain comprises a sequence having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more sequence identity to a sequence encoding the extracellular domain of a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit. In some embodiments, the extracellular domain comprises a sequence encoding the extracellular domain of a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit having a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more amino acids at the N- or C-terminus or at both the N- and C-terminus. [0571] The extracellular domain can be a TCR extracellular domain. The TCR extracellular domain can be derived from a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit or a CD3 delta TCR subunit. The extracellular domain can be a full-length TCR extracellular domain or fragment (e.g., functional fragment) thereof. The extracellular domain can comprise a variable domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The extracellular domain can comprise a variable domain and a constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. In some cases, the extracellular domain may not comprise a variable domain. [0572] The extracellular domain can comprise an extracellular portion of a constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The extracellular domain can comprise the extracellular portion of a full-length constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The extracellular domain can comprise a fragment (e.g., functional fragment) of the extracellular portion of the full-length constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. For example, the extracellular domain can comprise at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of the extracellular portion of the constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. [0573] The TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain described herein can be derived from various species. The TCR chain can be a murine or human TCR chain. For example, the extracellular domain can comprise a constant domain of a murine TCR alpha chain, a murine TCR beta chain, a human TCR gamma chain or a human TCR delta chain. Transmembrane Domain [0574] In general, a TFP sequence contains an extracellular domain and a transmembrane domain encoded by a single genomic sequence. In alternative embodiments, a TFP can be designed to comprise a transmembrane domain that is heterologous to the extracellular domain of the TFP. A transmembrane domain can include one or more additional amino acids adjacent to the transmembrane region, e.g., one or more amino acid associated with the extracellular region of the protein from which the transmembrane was derived (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more amino acids of the extracellular region) and/or one or more additional amino acids associated with the intracellular region of the protein from which the transmembrane protein is derived (e.g., 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or more amino acids of the intracellular region). In some cases, the transmembrane domain can include at least 30, 35, 40, 45, 50, 55, 60 or more amino acids of the extracellular region. In some cases, the transmembrane domain can include at least 30, 35, 40, 45, 50, 55, 60 or more amino acids of the intracellular region. In one aspect, the transmembrane domain is one that is associated with one of the other domains of the TFP is used. In some instances, the transmembrane domain can be selected or modified by amino acid substitution to avoid binding of such domains to the transmembrane domains of the same or different surface membrane proteins, e.g., to minimize interactions with other members of the receptor complex. In one aspect, the transmembrane domain is capable of homodimerization with another TFP on the TFP-T cell surface. In a different aspect the amino acid sequence of the transmembrane domain may be modified or substituted so as to minimize interactions with the binding domains of the native binding partner present in the same TFP. [0575] The transmembrane domain may be derived either from a natural or from a recombinant source. Where the source is natural, the domain may be derived from any membrane-bound or transmembrane protein. In one aspect the transmembrane domain is capable of signaling to the intracellular domain(s) whenever the TFP has bound to a target. In some instances, the TCR- integrating subunit comprises a transmembrane domain comprising a transmembrane domain of a protein selected from the group consisting of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a TCR zeta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, a CD3 delta TCR subunit, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD28, CD37, CD64, CD80, CD86, CD134, CD137, CD154, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0576] In some embodiments, the transmembrane domain comprises, or comprises at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 or more consecutive amino acid residues of the transmembrane domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit. In some embodiments, the transmembrane domain comprises a sequence having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more sequence identity to a sequence encoding the transmembrane domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit. In some embodiments, the transmembrane domain comprises a sequence encoding the transmembrane domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit having a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acids at the N- or C-terminus or at both the N- and C- terminus. [0577] In some instances, the transmembrane domain can be attached to the extracellular region of the TFP, e.g., the antigen binding domain of the TFP, via a hinge, e.g., a hinge from a human protein. For example, in one embodiment, the hinge can be a human immunoglobulin (Ig) hinge, e.g., an IgG4 hinge, or a CD8a hinge. Linkers [0578] Optionally, a short oligo- or polypeptide linker, between 2 and 10 amino acids in length may form the linkage between the binding element and the TCR extracellular domain of the TFP. A glycine-serine doublet provides a particularly suitable linker. In some cases, the linker may be at least about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or more in length. For example, in one aspect, the linker comprises the amino acid sequence of GGGGSGGGGS or a sequence (GGGGS)x wherein X is 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more. In some embodiments, X is 2. In some embodiments, X is 4. In some embodiments, the linker is encoded by a nucleotide sequence of GGTGGCGGAGGTTCTGGAGGTGGAGGTTCC. Cytoplasmic Domain [0579] The cytoplasmic domain of the TFP can include an intracellular domain. In some embodiments, the intracellular domain is from CD3 gamma, CD3 delta, CD3 epsilon, TCR alpha, TCR beta, TCR gamma, or TCR delta. In some embodiments, the intracellular domain comprises a signaling domain, if the TFP contains CD3 gamma, delta or epsilon polypeptides; TCR alpha, TCR beta, TCR gamma, and TCR delta subunits generally have short (e.g., 1-19 amino acids in length) intracellular domains and are generally lacking in a signaling domain. An intracellular signaling domain is generally responsible for activation of at least one of the normal effector functions of the immune cell in which the TFP has been introduced. While the intracellular domains of TCR alpha, TCR beta, TCR gamma, and TCR delta do not have signaling domains, they are able to recruit proteins having a primary intracellular signaling domain described herein, e.g., CD3 zeta, which functions as an intracellular signaling domain. The term “effector function” refers to a specialized function of a cell. Effector function of a T cell, for example, may be cytolytic activity or helper activity including the secretion of cytokines. Thus the term “intracellular signaling domain” refers to the portion of a protein which transduces the effector function signal and directs the cell to perform a specialized function. While usually the entire intracellular signaling domain can be employed, in many cases it is not necessary to use the entire chain. To the extent that a truncated portion of the intracellular signaling domain is used, such truncated portion may be used in place of the intact chain as long as it transduces the effector function signal. The term intracellular signaling domain is thus meant to include any truncated portion of the intracellular signaling domain sufficient to transduce the effector function signal. [0580] Examples of intracellular domains for use in the TFP of the present disclosure include the cytoplasmic sequences of the T cell receptor (TCR) and co-receptors that are able to act in concert to initiate signal transduction following antigen receptor engagement, as well as any derivative or variant of these sequences and any recombinant sequence that has the same functional capability. In some embodiments, the intracellular domain comprises the intracellular domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit. In some embodiments, the intracellular domain comprises, or comprises at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, or 19 or more consecutive amino acid residues of the intracellular domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, or a TCR delta chain. In some embodiments, the intracellular domain comprises a sequence having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more sequence identity to a sequence encoding the intracellular domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, or a TCR delta chain. In some embodiments, the transmembrane domain comprises a sequence encoding the intracellular domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, or a TCR delta chain having a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 or more amino acids at the N- or C-terminus or at both the N- and C-terminus. [0581] In some embodiments, the intracellular domain comprises, or comprises at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, or 62 or more consecutive amino acid residues of the intracellular domain of a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit. In some embodiments, the intracellular domain comprises a sequence having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% or more sequence identity to a sequence encoding the intracellular domain of a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit. In some embodiments, the intracellular domain comprises a sequence encoding the intracellular domain of a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, or a CD3 delta TCR subunit having a truncation of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or more amino acids at the N- or C-terminus or at both the N- and C-terminus. [0582] It is known that signals generated through the TCR alone are insufficient for full activation of naive T cells and that a secondary and/or costimulatory signal is required. Thus, naïve T cell activation can be said to be mediated by two distinct classes of cytoplasmic signaling sequences: those that initiate antigen-dependent primary activation through the TCR (primary intracellular signaling domains) and those that act in an antigen-independent manner to provide a secondary or costimulatory signal (secondary cytoplasmic domain, e.g., a costimulatory domain). [0583] A primary signaling domain regulates primary activation of the TCR complex either in a stimulatory way, or in an inhibitory way. Primary intracellular signaling domains that act in a stimulatory manner may contain signaling motifs which are known as immunoreceptor tyrosine- based activation motifs (ITAMs). [0584] Examples of ITAMs containing primary intracellular signaling domains that are of particular use in the present disclosure include those of CD3 zeta, FcR gamma, FcR beta, CD3 gamma, CD3 delta, CD3 epsilon, CD5, CD22, CD79a, CD79b, and CD66d. In one embodiment, a TFP of the present disclosure comprises an intracellular signaling domain, e.g., a primary signaling domain of CD3-epsilon. In one embodiment, a primary signaling domain comprises a modified ITAM domain, e.g., a mutated ITAM domain which has altered (e.g., increased or decreased) activity as compared to the native ITAM domain. In one embodiment, a primary signaling domain comprises a modified ITAM-containing primary intracellular signaling domain, e.g., an optimized and/or truncated ITAM-containing primary intracellular signaling domain. In an embodiment, a primary signaling domain comprises one, two, three, four or more ITAM motifs. [0585] The intracellular signaling domain of the TFP can comprise a CD3 signaling domain, e.g., CD3 epsilon, CD3 delta, CD3 gamma, or CD3 zeta, by itself or it can be combined with any other desired intracellular signaling domain(s) useful in the context of a TFP of the present disclosure. For example, the intracellular signaling domain of the TFP can comprise a CD3 epsilon chain portion and a costimulatory signaling domain. The costimulatory signaling domain refers to a portion of the TFP comprising the intracellular domain of a costimulatory molecule. A costimulatory molecule is a cell surface molecule other than an antigen receptor or its ligands that is required for an efficient response of lymphocytes to an antigen. Examples of such molecules include CD27, CD28, 4-1BB (CD137), OX40, CD30, CD40, PD1, ICOS, lymphocyte function-associated antigen-1 (LFA-1), CD2, CD7, LIGHT, NKG2C, B7-H3, and a ligand that specifically binds with CD83, and the like. For example, CD27 costimulation has been demonstrated to enhance expansion, effector function, and survival of human TFP-T cells in vitro and augments human T cell persistence and antitumor activity in vivo (Song et al., Blood. 2012; 119(3):696-706). [0586] The intracellular signaling sequences within the cytoplasmic portion of the TFP of the present disclosure may be linked to each other in a random or specified order. Optionally, a short oligo- or polypeptide linker, for example, between 2 and 10 amino acids (e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 amino acids) in length may form the linkage between intracellular signaling sequences. [0587] In one embodiment, a glycine-serine doublet can be used as a suitable linker. In one embodiment, a single amino acid, e.g., an alanine, a glycine, can be used as a suitable linker. [0588] In one aspect, the TFPs described herein may comprise a TCR extracellular domain, a TCR transmembrane domain, and a TCR intracellular domain, wherein at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit. In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from TCR alpha. In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from TCR beta. In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from TCR gamma. In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from TCR delta. In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from CD3 epsilon. In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from CD3 delta. In some embodiments, at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from CD3 gamma. [0589] In one aspect, the TFPs described herein may comprise a TCR extracellular domain, a TCR transmembrane domain, and a TCR intracellular domain, wherein all three of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from the same TCR subunit. In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from CD3 epsilon. In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from CD3 delta. In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain can be from CD3 gamma. In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain may comprise the constant domain of TCR alpha. In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain may comprise the constant domain of TCR beta. In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain may comprise the constant domain of TCR gamma. In some embodiments, the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain may comprise the constant domain of TCR delta. In some embodiments, the constant domain of TCR alpha or the constant domain of TCR beta may be murine. [0590] In one aspect, the cells expressing a TFP and an RNAi agent as described herein can further comprise a second TFP, e.g., a second TFP that includes a different antigen binding domain, e.g., to the same target (e.g., MSLN) or a different target (e.g., CD70, CD19, or MUC16). In one embodiment, when the cell expressing a TFP and an RNAi agent as described herein comprises two or more different TFPs, the antigen binding domains of the different TFPs can be such that the antigen binding domains do not interact with one another. For example, a cell expressing a first and second TFP can have an antigen binding domain of the first TFP, e.g., as a fragment, e.g., a scFv, that does not form an association with the antigen binding domain of the second TFP, e.g., the antigen binding domain of the second TFP is a VHH. [0591] In another aspect, the cells expressing a TFP and an RNAi agent as described herein can further express another agent, e.g., an agent which enhances the activity of a modified T cell. For example, in one embodiment, the agent can be an agent which inhibits an inhibitory molecule. Inhibitory molecules, e.g., PD1, can, in some embodiments, decrease the ability of a modified T cell to mount an immune effector response. Examples of inhibitory molecules include PD1, PD- L1, CTLA4, TIM3, LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 and TGFR beta. In one embodiment, the agent which inhibits an inhibitory molecule comprises a first polypeptide, e.g., an inhibitory molecule, associated with a second polypeptide that provides a positive signal to the cell, e.g., an intracellular signaling domain described herein. In one embodiment, the agent comprises a first polypeptide, e.g., of an inhibitory molecule such as PD1, LAG3, CTLA4, CD160, BTLA, LAIR1, TIM3, 2B4 and TIGIT, or a fragment of any of these (e.g., at least a portion of an extracellular domain of any of these), and a second polypeptide which is an intracellular signaling domain described herein (e.g., comprising a costimulatory domain (e.g., 4- 1BB, CD27 or CD28, e.g., as described herein) and/or a primary signaling domain (e.g., a CD3 zeta signaling domain described herein). In one embodiment, the agent comprises a first polypeptide of PD1 or a fragment thereof (e.g., at least a portion of an extracellular domain of PD1), and a second polypeptide of an intracellular signaling domain described herein (e.g., a CD28 signaling domain described herein and/or a CD3 zeta signaling domain described herein). In one particular embodiment, the agent comprises the extracellular and transmembrane domain of PD-1 fused to the intracellular signaling domain of CD28. In some embodiments, the agent comprises SEQ ID NO:370. PD1 is an inhibitory member of the CD28 family of receptors that also includes CD28, CTLA-4, ICOS, and BTLA. PD-1 is expressed on activated B cells, T cells and myeloid cells (Agata et al., 1996, Int. Immunol 8:765-75). Two ligands for PD1, PD-L1 and PD-L2, have been shown to downregulate T cell activation upon binding to PD1 (Freeman et al., 2000 J. Exp. Med.192:1027-34; Latchman et al., 2001 Nat. Immunol.2:261-8; Carter et al., 2002 Eur. J. Immunol.32:634-43). PD-L1 is abundant in human cancers (Dong et al., 2003 J. Mol. Med.81:281-7; Blank et al., 2005 Cancer Immunol. Immunother.54:307-314; Konishi et al., 2004 Clin. Cancer Res.10:5094). Immune suppression can be reversed by inhibiting the local interaction of PD1 with PD-L1. [0592] PD1CD28 fusion protein/switch-receptor, amino acid sequence (SEQ ID NO:370) MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSN TSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRN DSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVVGVVGG LLGSLVLLVWVLAVIRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS [0593] In one embodiment, the agent comprises the extracellular domain (ECD) of an inhibitory molecule, e.g., Programmed Death 1 (PD1) can be fused to a transmembrane domain and optionally an intracellular signaling domain such as 41BB and CD3 zeta (also referred to herein as a PD1 TFP). In one embodiment, the PD1 TFP, when used in combinations with an anti-TAA TFP described herein, improves the persistence of the T cell. In one embodiment, the TFP is a PD1 TFP comprising the extracellular domain of PD 1. Alternatively, provided are TFPs containing an antibody or antibody fragment such as a scFv that specifically binds to the Programmed Death-Ligand 1 (PD-L1) or Programmed Death-Ligand 2 (PD-L2). [0594] In another aspect, the present disclosure provides a population of immune cells, e.g., T cells, expressing a TFP and an RNAi agent or a sequence encoding the RNAi agent as described herein. In some embodiments, the population of immune cells, e.g., T cells expressing a TFP and an RNAi agent as described herein comprises a mixture of cells expressing different TFPs. For example, in one embodiment, the population of TFP-T cells can include a first cell expressing a TFP having a binding domain described herein, and a second cell expressing a TFP having a different anti-TAA binding domain, e.g., a binding domain described herein that differs from the binding domain in the TFP expressed by the first cell. As another example, the population of cells expressing a TFP and an RNAi agent as described herein can include a first cell expressing a TFP that includes a first binding domain binding domain, e.g., as described herein, and a second cell expressing a TFP that includes an antigen binding domain to a target other than the binding domain of the first cell (e.g., another tumor-associated antigen). [0595] In another aspect, the present disclosure provides a population of cells wherein at least one cell in the population expresses a TFP having a domain described herein, and a second cell expressing another agent, e.g., an agent which enhances the activity of a modified T cell. For example, in one embodiment, the agent can be an agent which inhibits an inhibitory molecule. Inhibitory molecules, e.g., can, in some embodiments, decrease the ability of a modified T cell to mount an immune effector response. Examples of inhibitory molecules include PD1, PD-L1, PD- L2, CTLA4, TIM3, LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 and TGFR beta. In one embodiment, the agent that inhibits an inhibitory molecule comprises a first polypeptide, e.g., an inhibitory molecule, associated with a second polypeptide that provides a positive signal to the cell, e.g., an intracellular signaling domain described herein. [0596] Disclosed herein are methods for producing in vitro transcribed RNA encoding TFPs and/or an RNAi agent as described herein. The present disclosure also includes a TFP and/or an RNAi agent encoding RNA construct that can be directly transfected into a cell. A method for generating mRNA for use in transfection can involve in vitro transcription (IVT) of a template with specially designed primers, followed by polyA addition, to produce a construct containing 3’ and 5’ untranslated sequence (“UTR”), a 5’ cap and/or Internal Ribosome Entry Site (IRES), the nucleic acid to be expressed, and a polyA tail, typically 50-2000 bases in length. RNA so produced can efficiently transfect different kinds of cells. In one aspect, the template includes sequences for the TFP and/or an RNAi agent. [0597] In one aspect the anti-TAA TFP is encoded by a messenger RNA (mRNA). In one aspect the mRNA encoding the anti-TAA TFP is introduced into a T cell for production of a TFP-T cell. In one embodiment, the in vitro transcribed RNA TFP can be introduced to a cell as a form of transient transfection. The RNA is produced by in vitro transcription using a polymerase chain reaction (PCR)-generated template. DNA of interest from any source can be directly converted by PCR into a template for in vitro mRNA synthesis using appropriate primers and RNA polymerase. The source of the DNA can be, for example, genomic DNA, plasmid DNA, phage DNA, cDNA, synthetic DNA sequence or any other appropriate source of DNA. The desired template for in vitro transcription is a TFP of the present disclosure. In one embodiment, the DNA to be used for PCR contains an open reading frame. The DNA can be from a naturally occurring DNA sequence from the genome of an organism. In one embodiment, the nucleic acid can include some or all of the 5’ and/or 3’ untranslated regions (UTRs). The nucleic acid can include exons and introns. In one embodiment, the DNA to be used for PCR is a human nucleic acid sequence. In another embodiment, the DNA to be used for PCR is a human nucleic acid sequence including the 5’ and 3’ UTRs. The DNA can alternatively be an artificial DNA sequence that is not normally expressed in a naturally occurring organism. An exemplary artificial DNA sequence is one that contains portions of genes that are ligated together to form an open reading frame that encodes a fusion protein. The portions of DNA that are ligated together can be from a single organism or from more than one organism. [0598] PCR is used to generate a template for in vitro transcription of mRNA which is used for transfection. Methods for performing PCR are well known in the art. Primers for use in PCR are designed to have regions that are substantially complementary to regions of the DNA to be used as a template for the PCR. “Substantially complementary,” as used herein, refers to sequences of nucleotides where a majority or all of the bases in the primer sequence are complementary, or one or more bases are non-complementary, or mismatched. Substantially complementary sequences are able to anneal or hybridize with the intended DNA target under annealing conditions used for PCR. The primers can be designed to be substantially complementary to any portion of the DNA template. For example, the primers can be designed to amplify the portion of a nucleic acid that is normally transcribed in cells (the open reading frame), including 5’ and 3’ UTRs. The primers can also be designed to amplify a portion of a nucleic acid that encodes a particular domain of interest. In one embodiment, the primers are designed to amplify the coding region of a human cDNA, including all or portions of the 5’ and 3’ UTRs. Primers useful for PCR can be generated by synthetic methods that are well known in the art. “Forward primers” are primers that contain a region of nucleotides that are substantially complementary to nucleotides on the DNA template that are upstream of the DNA sequence that is to be amplified. “Upstream” is used herein to refer to a location 5, to the DNA sequence to be amplified relative to the coding strand. “Reverse primers” are primers that contain a region of nucleotides that are substantially complementary to a double-stranded DNA template that are downstream of the DNA sequence that is to be amplified. “Downstream” is used herein to refer to a location 3’ to the DNA sequence to be amplified relative to the coding strand. [0599] Any DNA polymerase useful for PCR can be used in the methods disclosed herein. The reagents and polymerase are commercially available from a number of sources. [0600] Chemical structures with the ability to promote stability and/or translation efficiency may also be used. The RNA preferably has 5’ and 3’ UTRs. In one embodiment, the 5’ UTR is between one and 3000 nucleotides in length. The length of 5’ and 3’ UTR sequences to be added to the coding region can be altered by different methods, including, but not limited to, designing primers for PCR that anneal to different regions of the UTRs. Using this approach, one of ordinary skill in the art can modify the 5’ and 3’ UTR lengths required to achieve optimal translation efficiency following transfection of the transcribed RNA. [0601] The 5’ and 3’ UTRs can be the naturally occurring, endogenous 5’ and 3’ UTRs for the nucleic acid of interest. Alternatively, UTR sequences that are not endogenous to the nucleic acid of interest can be added by incorporating the UTR sequences into the forward and reverse primers or by any other modifications of the template. The use of UTR sequences that are not endogenous to the nucleic acid of interest can be useful for modifying the stability and/or translation efficiency of the RNA. For example, it is known that AU-rich elements in 3’UTR sequences can decrease the stability of mRNA. Therefore, 3’ UTRs can be selected or designed to increase the stability of the transcribed RNA based on properties of UTRs that are well known in the art. [0602] In one embodiment, the 5’ UTR can contain the Kozak sequence of the endogenous nucleic acid. Alternatively, when a 5’ UTR that is not endogenous to the nucleic acid of interest is being added by PCR as described above, a consensus Kozak sequence can be redesigned by adding the 5’ UTR sequence. Kozak sequences can increase the efficiency of translation of some RNA transcripts but do not appear to be required for all RNAs to enable efficient translation. The requirement for Kozak sequences for many mRNAs is known in the art. In other embodiments the 5’ UTR can be 5’UTR of an RNA virus whose RNA genome is stable in cells. In other embodiments various nucleotide analogues can be used in the 3’ or 5’ UTR to impede exonuclease degradation of the mRNA. [0603] To enable synthesis of RNA from a DNA template without the need for gene cloning, a promoter of transcription should be attached to the DNA template upstream of the sequence to be transcribed. When a sequence that functions as a promoter for an RNA polymerase is added to the 5’ end of the forward primer, the RNA polymerase promoter becomes incorporated into the PCR product upstream of the open reading frame that is to be transcribed. In one preferred embodiment, the promoter is a T7 polymerase promoter, as described elsewhere herein. Other useful promoters include, but are not limited to, T3 and SP6 RNA polymerase promoters. Consensus nucleotide sequences for T7, T3 and SP6 promoters are known in the art. [0604] In some embodiments, the mRNA has both a cap on the 5’ end and a 3’ poly(A) tail which determine ribosome binding, initiation of translation and stability mRNA in the cell. On a circular DNA template, for instance, plasmid DNA, RNA polymerase produces a long concatemeric product which is not suitable for expression in eukaryotic cells. The transcription of plasmid DNA linearized at the end of the 3’ UTR results in normal sized mRNA which is not effective in eukaryotic transfection even if it is polyadenylated after transcription. [0605] On a linear DNA template, phage T7 RNA polymerase can extend the 3’ end of the transcript beyond the last base of the template (Schenborn and Mierendorf, Nuc Acids Res., 13:6223-36 (1985); Nacheva and Berzal-Herranz, Eur. J. Biochem., 270:1485-65 (2003). [0606] The conventional method of integration of polyA/T stretches into a DNA template is molecular cloning. However, polyA/T sequence integrated into plasmid DNA can cause plasmid instability, which is why plasmid DNA templates obtained from bacterial cells are often highly contaminated with deletions and other aberrations. This makes cloning procedures not only laborious and time consuming but often not reliable. That is why a method which allows construction of DNA templates with polyA/T 3’ stretch without cloning highly desirable. [0607] The polyA/T segment of the transcriptional DNA template can be produced during PCR by using a reverse primer containing a poly-T tail, such as 100 T tail (size can be 50-5000 T), or after PCR by any other method, including, but not limited to, DNA ligation or in vitro recombination. Poly(A) tails also provide stability to RNAs and reduce their degradation. Generally, the length of a poly(A) tail positively correlates with the stability of the transcribed RNA. In one embodiment, the poly(A) tail is between 100 and 5000 adenosines. [0608] Poly(A) tails of RNAs can be further extended following in vitro transcription with the use of a poly(A) polymerase, such as E. coli polyA polymerase (E-PAP). In one embodiment, increasing the length of a poly(A) tail from 100 nucleotides to between 300 and 400 nucleotides results in about a two-fold increase in the translation efficiency of the RNA. Additionally, the attachment of different chemical groups to the 3’ end can increase mRNA stability. Such attachment can contain modified/artificial nucleotides, aptamers and other compounds. For example, ATP analogs can be incorporated into the poly(A) tail using poly(A) polymerase. ATP analogs can further increase the stability of the RNA. [0609] 5’ caps can also provide stability to RNA molecules. In some embodiments, RNAs produced by the methods disclosed herein include a 5’ cap. The 5’ cap is provided using techniques known in the art and described herein (Cougot, et al., Trends in Biochem. Sci., 29:436-444 (2001); Stepinski, et al., RNA, 7:1468-95 (2001); Elango, et al., Biochim. Biophys. Res. Commun., 330:958-966 (2005)). [0610] The RNAs produced by the methods disclosed herein can also contain an internal ribosome entry site (IRES) sequence. The IRES sequence may be any viral, chromosomal or artificially designed sequence which initiates cap-independent ribosome binding to mRNA and facilitates the initiation of translation. Any solutes suitable for cell electroporation, which can contain factors facilitating cellular permeability and viability such as sugars, peptides, lipids, proteins, antioxidants, and surfactants can be included. [0611] RNA can be introduced into target cells using any of a number of different methods, for instance, commercially available methods which include, but are not limited to, electroporation (Amaxa Nucleofector®-II (Amaxa Biosystems, Cologne, Germany)), ECM 830 (BTX) (Harvard Instruments, Boston, Mass.) or the Gene Pulser® II (BioRad, Denver, Colo.), Multiporator® (Eppendorf, Hamburg Germany), cationic liposome mediated transfection using lipofection, polymer encapsulation, peptide mediated transfection, or biolistic particle delivery systems such as “gene guns” (see, for example, Nishikawa, et al. Hum Gene Ther., 12(8):861-70 (2001). Recombinant Nucleic Acid Encoding a TFP and a TCR Constant Domain [0612] Disclosed herein, in some embodiments, are recombinant nucleic acid molecules comprising a sequence encoding a T cell receptor (TCR) fusion protein (TFP). The TFP can comprise a TCR subunit comprising at least a portion of a TCR extracellular domain. The TCR subunit can further comprise a transmembrane domain. The TCR subunit can further comprise an intracellular domain of TCR gamma, TCR delta, TCR alpha or TCR beta or an intracellular domain comprising a stimulatory domain from an intracellular signaling domain of CD3 epsilon, CD3 gamma, CD3 delta. The TFP can further comprise an antibody (e.g., a human, humanized, or murine antibody) comprising an antigen binding domain. The recombinant nucleic acid molecule can further comprise a sequence encoding a TCR constant domain, wherein the TCR constant domain is a TCR alpha constant domain, a TCR beta constant domain, a TCR alpha constant domain and a TCR beta constant domain, a TCR gamma constant domain, a TCR delta constant domain, or a TCR gamma constant domain and a TCR delta constant domain. The TCR subunit and the antibody can be operatively linked. The TFP can functionally incorporate into a TCR complex (e.g., an endogenous TCR complex) when expressed in a T cell. [0613] The constant domain can comprise a constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The constant domain can comprise a full-length constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The constant domain can comprise a fragment (e.g., functional fragment) of the full-length constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. For example, the constant domain can comprise at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of the constant domain of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The sequence encoding the TCR constant domain can further encode the transmembrane domain and/or intracellular region of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The sequence encoding the TCR constant domain can encode a full-length constant region of a TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. The constant region of a TCR chain can comprise a constant domain, a transmembrane domain, and an intracellular region. The constant region of a TCR chain can also exclude the transmembrane domain and the intracellular region of the TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain. [0614] The TCR alpha chain, a TCR beta chain, a TCR gamma chain or a TCR delta chain described herein can be derived from various species. The TCR chain can be a murine or human TCR chain. For example, the constant domain can comprise a constant domain of a murine or human TCR alpha chain, TCR beta chain, TCR gamma chain or TCR delta chain. [0615] The constant domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the constant domain can comprise a truncated version of a constant domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, SEQ ID NO:155, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:243 or SEQ ID NO:265. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, SEQ ID NO:155, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:243 or SEQ ID NO:265. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, SEQ ID NO:155, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:243 or SEQ ID NO:265. The constant domain can comprise a sequence or fragment thereof of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, SEQ ID NO:155, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:243 or SEQ ID NO:265. The constant domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, SEQ ID NO:155, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:243 or SEQ ID NO:265. The constant domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, SEQ ID NO:155, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:243 or SEQ ID NO:265. The constant domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO:18, SEQ ID NO:19, SEQ ID NO:20, SEQ ID NO:21, or SEQ ID NO:22, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, SEQ ID NO:155, SEQ ID NO:207, SEQ ID NO:209, SEQ ID NO:243 or SEQ ID NO:265. [0616] The murine TCR alpha constant domain can comprise positions 2-137 of SEQ ID NO:146. The murine TCR alpha constant domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the constant domain can comprise a truncated version of a constant domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of positions 2-137 of SEQ ID NO:146. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of positions 2-137 of SEQ ID NO:146. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of positions 2-137 of SEQ ID NO:146. The constant domain can comprise a sequence or fragment thereof of positions 2-137 of SEQ ID NO:146. The constant domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of positions 2-137 of SEQ ID NO:146. The constant domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of positions 2-137 of SEQ ID NO:146. The constant domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of positions 2-137 of SEQ ID NO:146. [0617] The murine TCR beta constant domain can comprise positions 2-173 of SEQ ID NO:152. The murine TCR beta constant domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the constant domain can comprise a truncated version of a constant domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of positions 2-173 of SEQ ID NO:152. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of positions 2-173 of SEQ ID NO:152. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of positions 2-173 of SEQ ID NO:152. The constant domain can comprise a sequence or fragment thereof of positions 22-173 of SEQ ID NO:152. The constant domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of positions 2-173 of SEQ ID NO:152. The constant domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of positions 2-173 of SEQ ID NO:152. The constant domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of positions 2-173 of SEQ ID NO:152. [0618] In some instances, the TCR constant domain is a TCR delta constant domain. The TCR delta constant domain can comprise SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:243 or SEQ ID NO:265, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modification. In some embodiments, the TCR delta constant domain can comprise SEQ ID NO:243. The TCR delta constant domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the constant domain can comprise a truncated version of a constant domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of SEQ ID NO:243. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of SEQ ID NO:243. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of SEQ ID NO:243. The constant domain can comprise a sequence or fragment thereof of SEQ ID NO:243. The constant domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of SEQ ID NO:243. The constant domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of SEQ ID NO:243. The constant domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of SEQ ID NO:243. In some embodiments, the TCR delta constant domain can comprise SEQ ID NO:265. The TCR delta constant domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the constant domain can comprise a truncated version of a constant domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of SEQ ID NO:265. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of SEQ ID NO:265. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of SEQ ID NO:265. The constant domain can comprise a sequence or fragment thereof of SEQ ID NO:265. The constant domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of SEQ ID NO:265. The constant domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of SEQ ID NO:265. The constant domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of SEQ ID NO:265. [0619] The TCR delta constant domain can comprise SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:243 or SEQ ID NO:265, functional fragments thereof, or amino acid sequences thereof having at least one but not more than 20 modifications. In some cases, the sequence encoding a TCR delta constant domain further encodes a TCR delta variable domain, thereby encoding a full TCR delta domain. The full TCR delta domain can be delta 2 or delta 1. The full TCR delta constant domain can comprise SEQ ID NO:256, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0620] The full TCR delta domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the delta domain can comprise a truncated version of a delta domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of SEQ ID NO:256. For example, the delta domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of SEQ ID NO:256. For example, the delta domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of SEQ ID NO:256. The delta domain can comprise a sequence or fragment thereof of SEQ ID NO:256. The delta domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of SEQ ID NO:256. The delta domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of SEQ ID NO:256. The delta domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of SEQ ID NO:256. [0621] The TCR gamma constant domain can comprise SEQ ID NO:21. The TCR gamma constant domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the constant domain can comprise a truncated version of a constant domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of SEQ ID NO:21. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of SEQ ID NO:21. For example, the constant domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of SEQ ID NO:21. The constant domain can comprise a sequence or fragment thereof of SEQ ID NO:21. The constant domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or deletions of the sequence of SEQ ID NO:21. The constant domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of SEQ ID NO:21. The constant domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of SEQ ID NO:21. [0622] The TCR gamma constant domain can comprise SEQ ID NO:21 or SEQ ID NO:155, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. In some cases, the sequence encoding the TCR gamma constant domain further encodes a TCR gamma variable domain, thereby encoding a full TCR gamma domain. The full TCR gamma domain can be gamma 9 or gamma 4. The full TCR gamma domain can comprise SEQ ID NO:255, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0623] The full TCR gamma domain can comprise truncations, additions, or substitutions of a sequence of a constant domain described herein. For example, the gamma domain can comprise a truncated version of a gamma domain described herein having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid residues of SEQ ID NO:255. For example, the gamma domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more additional amino acid residues of SEQ ID NO:255. For example, the gamma domain can comprise a sequence having at least about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 150 or more amino acid substitutions of SEQ ID NO:255. The gamma domain can comprise a sequence or fragment thereof of SEQ ID NO:255. The gamma domain can comprise at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more modifications, mutations or gamma of the sequence of SEQ ID NO:255. The gamma domain can comprise at most 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 modification, mutations or deletions of the sequence of SEQ ID NO:255. The gamma domain can comprise a sequence having a sequence identity of at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% to the sequence of SEQ ID NO:255. [0624] TCR beta chain (Homo sapiens): VEDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVST DPQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKP VTQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKR KDF (SEQ ID NO:16). [0625] The murine TCR beta chain constant region canonical sequence is: EDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTD PQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNIS AEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS (SEQ ID NO:152). [0626] TCR alpha constant region (Mus musculus) (or [mm]TRAC(82-137)): ATYPSSDVPCDATLTEKSFETDMNLNFQNLSVMGLRILLLKVAGFNLLMTLRLWSS (SEQ ID NO:17). [0627] The murine TCR alpha chain constant (mTRAC) region canonical sequence is: XIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKSN GAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLSVMGLRILL LKVAGFNLLMTLRLWSS (SEQ ID NO:146). [0628] TCR beta constant region (Mus musculus) (or [mm]TRBC1(123-173)): GRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS (SEQ ID NO:18). [0629] The murine TCR beta chain constant region canonical sequence is: EDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTD PQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNIS AEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS (SEQ ID NO:152). [0630] TCR beta chain (Homo sapiens): PVDSGVTQTPKHLITATGQRVTLRCSPRSGDLSVSWYQQSLDQGLQFLIQYYNGEERAK GNILERFSAQQFPDLHSELNLSSLELGDSALYFCASSPRTGLNTEAFFGQGTRLTVVEDLN KVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTDPQPL KEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVTQIV SAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDF (SEQ ID NO:19). [0631] TCR delta constant region version 1 (Homo sapiens): SQPHTKPSVFVMKNGTNVACLVKEFYPKDIRINLVSSKKITEFDPAIVISPSGKYNAVKLG KYEDSNSVTCSVQHDNKTVHSTDFEVKTDSTDHVKPKETENTKQPSKSCHKPKAIVHTE KVNMMSLTVLGLRMLFAKTVAVNFLLTAKLFF (SEQ ID NO:20). [0632] TCR gamma constant region (Homo sapiens) (or [hs]TRGC(1-173)): DKQLDADVSPKPTIFLPSIAETKLQKAGTYLCLLEKFFPDVIKIHWQEKKSNTILGSQEGN TMKTNDTYMKFSWLTVPEKSLDKEHRCIVRHENNKNGVDQEIIFPPIKTDVITMDPKDN CSKDANDTLLLQLTNTSAYYMYLLLLLKSVVYFAIITCCLLRRTAFCCNGEKS (SEQ ID NO:21). [0633] TCR delta constant region version 2 (Homo sapiens): SQPHTKPSVFVMKNGTNVACLVKEFYPKDIRINLVSSKKITEFDPAIVISPSGKYNAVKLG KYEDSNSVTCSVQHDNKTVHSTDFEVKTDSTDHVKPKETENTKQPSKSCHKPKAIVHTE KVNMMSLTVLGLRMLFAKTVAVNFLLTAK (SEQ ID NO:22). [0634] In some instances, the TCR constant domain is a TCR delta constant domain. The sequence encoding the TCR delta constant domain can further encode a second antigen binding domain or ligand binding domain that is operatively linked to the sequence encoding the TCR delta constant domain. The second antigen binding domain or ligand binding domain can be the same or different as the antigen binding domain or ligand binding domain of the TFP. [0635] In some instances, the TCR constant domain is a TCR gamma constant domain. The sequence encoding the TCR gamma constant domain can further encode a second antigen binding domain or ligand binding domain that is operatively linked to the sequence encoding the TCR gamma constant domain. The second antigen binding domain or ligand binding domain can be the same or different as the antigen binding domain or ligand binding domain of the TFP. [0636] In some instances, the recombinant nucleic acid comprises a sequence encoding a TCR gamma constant domain and a TCR delta constant domain. The TCR gamma constant domain can comprise SEQ ID NO:21 or SEQ ID NO:155, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The sequence encoding the TCR gamma constant domain can further encode a TCR gamma variable domain, thereby encoding a full TCR gamma domain. The TCR gamma domain can be gamma 9 or gamma 4. The full TCR gamma domain comprises SEQ ID NO:255, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The TCR delta constant domain can comprise SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:243 or SEQ ID NO:265, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The sequence encoding the TCR delta constant domain can further encode a TCR delta variable domain, thereby encoding a full TCR delta domain. The TCR delta domain can be delta 2 or delta 1. The full TCR delta domain can comprise SEQ ID NO:256, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0637] In some instances, the TCR constant domain incorporates into a functional TCR complex when expressed in a T cell. In some instances, the TCR constant domain incorporates into a same functional TCR complex as the functional TCR complex that incorporates the TFP when expressed in a T cell. In some instances, the sequence encoding the TFP and the sequence encoding the TCR constant domain are contained within a same nucleic acid molecule. In some instances, the sequence encoding the TFP and the sequence encoding the TCR constant domain are contained within different nucleic acid molecules. The sequence can further encode a cleavage site (e.g., a protease cleavage site) between the encoded TFP and the TCR constant domain. The cleavage site can be a protease cleavage site. The cleavage site can be a self- cleaving peptide such as a T2A, P2A, E2A or F2A cleavage site. The cleavage site can comprise a sequence of SEQ ID NO:23. [0638] T2A cleavage site: EGRGSLLTCGDVEENPGP (SEQ ID NO:23). [0639] The TCR subunit of the TFP and the constant domain can comprise a sequence derived from a same TCR chain or a different TCR chain. In some cases, the TCR subunit of the TFP and the constant domain are derived from different TCR chains. For example, the TCR subunit can comprise (1) at least a portion of a TCR extracellular domain, (2) a transmembrane domain, and (3) an intracellular domain, where the TCR extracellular domain, the transmembrane domain and the intracellular domain are derived from a TCR alpha chain, and the constant domain can comprise a constant domain of a TCR beta chain. For another example, the TCR subunit can comprise (1) at least a portion of a TCR extracellular domain, (2) a transmembrane domain, and (3) an intracellular domain, where the TCR extracellular domain, the transmembrane domain and the intracellular domain are derived from a TCR beta chain, and the constant domain can comprise a constant domain of a TCR alpha chain. For another example, the TCR subunit can comprise (1) at least a portion of a TCR extracellular domain, (2) a transmembrane domain, and (3) an intracellular domain, where the TCR extracellular domain, the transmembrane domain and the intracellular domain are derived from a TCR gamma chain, and the constant domain can comprise a constant domain of a TCR delta chain. For yet another example, the TCR subunit can comprise (1) at least a portion of a TCR extracellular domain, (2) a transmembrane domain, and (3) an intracellular domain, where the TCR extracellular domain, the transmembrane domain and the intracellular domain are derived from a TCR delta chain, and the constant domain can comprise a constant domain of a TCR gamma chain. [0640] In some instances, the TCR subunit and the antibody domain, the antigen domain or the binding ligand or fragment thereof are operatively linked by a linker sequence. In some instances, the linker sequence comprises (G4S)n, wherein n=1 to 4. [0641] In some instances, the transmembrane domain is a TCR transmembrane domain from CD3 epsilon, CD3 gamma, CD3 delta, TCR gamma, TCR delta, TCR alpha or TCR beta. In some instances, the intracellular domain is derived from only CD3 epsilon, only CD3 gamma, only CD3 delta, only TCR gamma, only TCR delta, only TCR alpha or only TCR beta. [0642] In some instances, the TCR subunit comprises (i) at least a portion of a TCR extracellular domain, (ii) a TCR transmembrane domain, and (iii) a TCR intracellular domain, wherein at least two or all of (i), (ii), and (iii) are from the same TCR subunit. [0643] In some instances, the TCR extracellular domain comprises an extracellular domain or portion thereof of a protein selected from the group consisting of a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, a CD3 delta TCR subunit, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0644] In some instances, the TCR subunit comprises a transmembrane domain comprising a transmembrane domain of a protein selected from the group consisting of a TCR alpha chain, a TCR beta chain, a TCR zeta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, a CD3 delta TCR subunit, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD28, CD37, CD64, CD80, CD86, CD134, CD137, CD154, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0645] In some instances, the TCR subunit comprises a TCR intracellular domain of TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, or a fragment thereof. In some instances, the TCR subunit comprises an intracellular domain comprising a stimulatory domain of a protein selected from an intracellular signaling domain of CD3 epsilon, CD3 gamma or CD3 delta, or an amino acid sequence having at least one modification thereto. [0646] In some instances, the TCR subunit can comprise (i) at least a portion of a TCR extracellular domain, (ii) a TCR transmembrane domain, and (iii) a TCR intracellular domain of a TCR gamma chain or a TCR delta chain. The TCR extracellular domain can comprise the extracellular portion of a constant domain of a TCR gamma chain or a TCR delta chain, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. In some embodiments, the TCR subunit comprising (i) at least a portion of a TCR extracellular domain, (ii) a TCR transmembrane domain, and (iii) a TCR intracellular domain is or comprises a delta constant domain, or a fragment thereof, e.g., a delta constant domain described herein. The delta constant domain can have the sequence of SEQ ID NO:20, SEQ ID NO:22, SEQ ID NO:243 or SEQ ID NO:265, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. In some embodiments, the TCR subunit comprising (i) at least a portion of a TCR extracellular domain, (ii) a TCR transmembrane domain, and (iii) a TCR intracellular domain is or comprises a gamma constant domain, e.g., a gamma constant domain described herein. The gamma constant domain can have the sequence of SEQ ID NO:21 or SEQ ID NO:155, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The extracellular domain of the TFP may not comprise the variable domain of a gamma chain or a delta chain. [0647] The TCR subunit of the TFP can comprise the extracellular, transmembrane and intracellular domain of CD3 epsilon, CD3 gamma, or CD3 delta. In some embodiments, recombinant nucleic acid comprises a TFP comprising the extracellular, transmembrane and intracellular domain of CD3 epsilon, CD3 gamma, or CD3 delta and the constant domains of TCR beta and TCR alpha. In some embodiments, recombinant nucleic acid comprises a TFP comprising the extracellular, transmembrane and intracellular domain of CD3 epsilon and the constant domains of TCR gamma and TCR delta. In some embodiments, recombinant nucleic acid comprises a TFP comprising the extracellular, transmembrane and intracellular domain of CD3 epsilon and full length TCF gamma and full length TCR delta. In some embodiments, the TCR subunit of the TFP comprises CD3 epsilon. The TCR subunit of CD3 epsilon can comprise the sequence of SEQ ID NO:258 functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0648] In some instances, the TCR subunit comprising at least a portion of a murine TCR alpha or murine TCR beta extracellular domain and a murine TCR alpha or murine TCR beta transmembrane domain is or comprises a TCR alpha constant domain or a TCR beta constant domain. The TCR subunit can comprise an intracellular domain of murine TCR alpha or murine TCR beta. The TCR constant domain can be a TCR alpha constant domain, e.g., a TCR alpha constant domain described herein. The TCR alpha constant domain can comprise SEQ ID NO:17, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, or SEQ ID NO:207, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The sequence encoding the TCR alpha constant domain can further encode a second antigen binding domain or ligand binding domain that is operatively linked to the sequence encoding the TCR alpha constant domain. The second antigen binding domain or ligand binding domain can be the same or different as the antigen binding domain or ligand binding domain of the TFP. The TCR alpha constant domain can comprise a murine TCR alpha constant domain. The murine TCR alpha constant domain can comprise amino acids 2-137 of the murine TCR alpha constant domain. The murine TCR alpha constant domain can comprise amino acids 2-137 of SEQ ID NO:146. The murine TCR alpha constant domain can comprise a sequence of SEQ ID NO:207. The murine TCR alpha constant domain can comprise amino acids 82-137 of SEQ ID NO:146. The murine TCR alpha constant domain comprises a sequence of SEQ ID NO:17. The TCR constant domain can be a TCR beta constant domain, e.g., a TCR beta constant domain described herein. The TCR beta constant domain can comprise SEQ ID NO:18, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, or SEQ ID NO:209, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The sequence encoding the TCR beta constant domain can further encode a second antigen binding domain or ligand binding domain that is operatively linked to the sequence encoding the TCR beta constant domain. The second antigen binding domain or ligand binding domain can be the same or different as the antigen binding domain or ligand binding domain of the TFP. TCR beta constant domain can comprise a murine TCR beta constant domain. The murine TCR beta constant domain can comprise amino acids 2-173 of the murine TCR beta constant domain. The murine TCR beta constant domain can comprise amino acids 2- 173 of SEQ ID NO:152. The murine TCR beta constant domain can comprise SEQ ID NO:209. The TCR beta constant domain can comprise amino acids 123-173 of SEQ ID NO:152. The TCR beta constant domain can comprise SEQ ID NO:18. [0649] The recombinant nucleic acid can comprise sequence encoding a TCR alpha constant domain and a TCR beta constant domain. The TCR alpha constant domain can comprise SEQ ID NO:17, SEQ ID NO:142, SEQ ID NO:143, SEQ ID NO:146, or SEQ ID NO:207, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The TCR beta constant domain can comprise SEQ ID NO:18, SEQ ID NO:148, SEQ ID NO:149, SEQ ID NO:152, or SEQ ID NO:209, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. The intracellular signaling domain can be CD3 epsilon, CD3 gamma, or CD3 delta. The intracellular signaling domain can be CD3 epsilon. [0650] The sequence encoding the TCR constant domain can comprise from 5’ to 3’, a first leader sequence, an antigen binding domain sequence, a linker, a TRAC gene sequence, a cleavable linker sequence, a second leader sequence, and a TRBC gene sequence. The sequence encoding the TCR constant domain can comprise, from 5’ to 3’, a first leader sequence, an antigen binding domain sequence, a linker, a TRAC gene sequence, a cleavable linker sequence, a second leader sequence, and a TRBC gene sequence. The sequence encoding the TCR constant domain can comprise, from 5’ to 3’, a first leader sequence, a TRAC gene sequence, a cleavable linker sequence, a second leader sequence, an antigen binding domain sequence, a linker, and a TRBC gene sequence. The sequence encoding the TCR constant domain can comprise, from 5’ to 3’, a first leader sequence, an antigen binding domain sequence, a linker, a TRAC gene sequence, a cleavable linker sequence, a second leader sequence, an antigen binding domain sequence, a linker, and a TRBC gene sequence. The sequence encoding the TCR constant domain can comprise, from 5’-3’, a first leader sequence, a TRAC gene sequence, a first cleavable linker sequence, a second leader sequence, a TRBC gene sequence, a second cleavable linker sequence, a third leader sequence, an antigen binding domain sequence, a linker sequence, and a CD3 epsilon gene sequence. [0651] As described herein, the at least one but not more than 20 modifications thereto of a sequence described herein can comprise a modification of an amino acid that mediates cell signaling or a modification of an amino acid that is phosphorylated in response to a ligand binding to the TFP. [0652] In some instances, the TCR subunit comprises an intracellular domain comprising a stimulatory domain of a protein selected from a functional signaling domain of 4-1BB and/or a functional signaling domain of CD3 zeta, or an amino acid sequence having at least one modification thereto. [0653] In some instances, the recombinant nucleic acid further comprises a sequence encoding a costimulatory domain. In some instances, the costimulatory domain comprises a functional signaling domain of a protein selected from the group consisting of OX40, CD2, CD27, CD28, CDS, ICAM-1, LFA-1 (CD11a/CD18), ICOS (CD278), and 4-1BB (CD137), and amino acid sequences thereof having at least one but not more than 20 modifications thereto. [0654] In some instances, the TCR subunit comprises an immunoreceptor tyrosine-based activation motif (ITAM) of a TCR subunit that comprises an ITAM or portion thereof of a protein selected from the group consisting of CD3 zeta TCR subunit, CD3 epsilon TCR subunit, CD3 gamma TCR subunit, CD3 delta TCR subunit, TCR zeta chain, Fc epsilon receptor 1 chain, Fc epsilon receptor 2 chain, Fc gamma receptor 1 chain, Fc gamma receptor 2a chain, Fc gamma receptor 2b1 chain, Fc gamma receptor 2b2 chain, Fc gamma receptor 3a chain, Fc gamma receptor 3b chain, Fc beta receptor 1 chain, TYROBP (DAP12), CD5, CD16a, CD16b, CD22, CD23, CD32, CD64, CD79a, CD79b, CD89, CD278, CD66d, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications thereto. In some instances, the ITAM replaces an ITAM of CD3 gamma, CD3 delta, or CD3 epsilon. In some instances, the ITAM is selected from the group consisting of CD3 zeta TCR subunit, CD3 epsilon TCR subunit, CD3 gamma TCR subunit, and CD3 delta TCR subunit and replaces a different ITAM selected from the group consisting of CD3 zeta TCR subunit, CD3 epsilon TCR subunit, CD3 gamma TCR subunit, and CD3 delta TCR subunit. [0655] In some instances, the TFP, the TCR gamma constant domain, the TCR delta constant domain, and any combination thereof is capable of functionally interacting with an endogenous TCR complex and/or at least one endogenous TCR polypeptide. In some instances, (a) the TCR constant domain is a TCR gamma constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR delta, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; (b) the TCR constant domain is a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR gamma, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; or (c) the TCR constant domain is a TCR gamma constant domain and a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof. [0656] In some instances, the at least one but not more than 20 modifications thereto comprise a modification of an amino acid that mediates cell signaling or a modification of an amino acid that is phosphorylated in response to a ligand binding to the TFP. [0657] The antibody or antigen binding domain can be an antibody fragment. The antibody or antigen binding domain can be murine, human or humanized. In some instances, the murine, human or humanized antibody is an antibody fragment. In some instances, the antibody fragment is a scFv, a single domain antibody domain, a VH domain or a VL domain. [0658] An antigen binding domain described herein can be selected from a group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, an anti-79b binding domain, , an anti-PMSA binding domain, an anti-MUC16 binding domain, an anti-CD22 binding domain, an anti-PD-L1 binding domain, an anti BAFF receptor binding domain, an anti-Nectin-4 binding domain, an anti-TROP-2 binding domain, an anti- GPC3 binding domain, and anti-ROR-1 binding domain. [0659] In some instances, the nucleic acid is selected from the group consisting of a DNA and an RNA. In some instances, the nucleic acid is an mRNA. In some instances, the recombinant nucleic acid comprises a nucleic acid analog, wherein the nucleic acid analog is not in an encoding sequence of the recombinant nucleic acid. In some instances, the nucleic analog is selected from the group consisting of 2’-O-methyl, 2’-O-methoxyethyl (2’-O-MOE), 2’-O- aminopropyl, 2’-deoxy, T-deoxy-2’-fluoro, 2’-O-aminopropyl (2’-O-AP), 2'-O- dimethylaminoethyl (2’-O-DMAOE), 2’-O-dimethylaminopropyl (2’-O-DMAP), T-O- dimethylaminoethyloxyethyl (2’-O-DMAEOE), 2’-O-N-methylacetamido (2’-O-NMA) modified, a locked nucleic acid (LNA), an ethylene nucleic acid (ENA), a peptide nucleic acid (PNA), a 1’,5’- anhydrohexitol nucleic acid (HNA), a morpholino, a methylphosphonate nucleotide, a thiolphosphonate nucleotide, and a 2’-fluoro N3-P5’-phosphoramidite. [0660] In some instances, the recombinant nucleic acid further comprises a leader sequence. In some instances, the recombinant nucleic acid further comprises a promoter sequence. In some instances, the recombinant nucleic acid further comprises a sequence encoding a poly(A) tail. In some instances, the recombinant nucleic acid further comprises a 3’UTR sequence. In some instances, the nucleic acid is an isolated nucleic acid or a non-naturally occurring nucleic acid. In some instances, the nucleic acid is an in vitro transcribed nucleic acid. [0661] In some instances, the recombinant nucleic acid further comprises a sequence encoding a TCR alpha transmembrane domain. In some instances, the recombinant nucleic acid further comprises a sequence encoding a TCR beta transmembrane domain. In some instances, the recombinant nucleic acid further comprises a sequence encoding a TCR alpha transmembrane domain and a sequence encoding a TCR beta transmembrane domain. [0662] In some instances, the TCR subunit comprises an immunoreceptor tyrosine-based activation motif (ITAM) of a TCR subunit that comprises an ITAM or portion thereof of a protein selected from the group consisting of CD3 zeta TCR subunit, CD3 epsilon TCR subunit, CD3 gamma TCR subunit, CD3 delta TCR subunit, TCR zeta chain, Fc epsilon receptor 1 chain, Fc epsilon receptor 2 chain, Fc gamma receptor 1 chain, Fc gamma receptor 2a chain, Fc gamma receptor 2b1 chain, Fc gamma receptor 2b2 chain, Fc gamma receptor 3a chain, Fc gamma receptor 3b chain, Fc beta receptor 1 chain, TYROBP (DAP12), CD5, CD16a, CD16b, CD22, CD23, CD32, CD64, CD79a, CD79b, CD89, CD278, CD66d, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications thereto. In some instances, the ITAM replaces an ITAM of CD3 gamma, CD3 delta, or CD3 epsilon. In some instances, the ITAM is selected from the group consisting of CD3 zeta TCR subunit, CD3 epsilon TCR subunit, CD3 gamma TCR subunit, and CD3 delta TCR subunit and replaces a different ITAM selected from the group consisting of CD3 zeta TCR subunit, CD3 epsilon TCR subunit, CD3 gamma TCR subunit, and CD3 delta TCR subunit. [0663] In some instances, the TFP, the TCR gamma constant domain, the TCR delta constant domain, the TCR alpha constant domain, the TCR beta constant domain, and any combination thereof is capable of functionally interacting with an endogenous TCR complex and/or at least one endogenous TCR polypeptide. In some instances, (a) the TCR constant domain is a TCR gamma constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR beta, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; (b) the TCR constant domain is a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR alpha, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; (c) the TCR constant domain is a TCR gamma constant domain and a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; (d) the TCR constant domain is a TCR alpha constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR beta, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; or (e) the TCR constant domain is a TCR beta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR alpha, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof. [0664] In some instances, the at least one but not more than 20 modifications thereto comprise a modification of an amino acid that mediates cell signaling or a modification of an amino acid that is phosphorylated in response to a ligand binding to the TFP. [0665] In some instances, the murine, human or humanized antibody is an antibody fragment. In some instances, the antibody fragment is a scFv, a single domain antibody domain (sdAb), a VH domain or a VL domain. [0666] In some instances, murine, human or humanized antibody comprising an antigen binding domain. The antigen binding domain described herein can be selected from a group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, an anti-79b binding domain, , an anti-PMSA binding domain, an anti-MUC16 binding domain, an anti-CD22 binding domain, an anti-PD-L1 binding domain, an anti BAFF receptor binding domain, an anti-Nectin-4 binding domain, an anti-TROP-2 binding domain, an anti- GPC3 binding domain, and anti-ROR-1 binding domain. [0667] In some instances, the antigen binding domain comprises a ligand. In some instances, the ligand binds to the receptor of a cell. In some instances, the ligand binds to the polypeptide expressed on a surface of a cell. In some instances, the receptor or polypeptide expressed on a surface of a cell comprises a stress response receptor or polypeptide. In some instances, the receptor or polypeptide expressed on a surface of a cell is an MHC class I-related glycoprotein. In some instances, the MHC class I-related glycoprotein is selected from the group consisting of MICA, MICB, RAET1E, RAET1G, ULBP1, ULBP2, ULBP3, ULBP4 and combinations thereof. In some instances, the antigen domain comprises a monomer, a dimer, a trimer, a tetramer, a pentamer, a hexamer, a heptamer, an octomer, a nonamer, or a decamer. In some instances, the antigen domain comprises a monomer or a dimer of the ligand or fragment thereof. In some instances, the ligand or fragment thereof is a monomer, a dimer, a trimer, a tetramer, a pentamer, a hexamer, a heptamer, an octomer, a nonamer, or a decamer. In some instances, the ligand or fragment thereof is a monomer or a dimer. In some instances, the antigen domain does not comprise an antibody or fragment thereof. In some instances, the antigen domain does not comprise a variable region. In some instances, the antigen domain does not comprise a CDR. In some instances, the ligand or fragment thereof is a Natural Killer Group 2D (NKG2D) ligand or a fragment thereof. [0668] In some instances, the TCR subunit and the antibody domain, the antigen domain or the binding ligand or fragment thereof are operatively linked by a linker sequence. In some instances, the linker sequence comprises (G4S)n, wherein n=1 to 4. [0669] In some instances, the transmembrane domain is a TCR transmembrane domain from CD3 epsilon, CD3 gamma, CD3 delta, TCR alpha, TCR beta, TCR delta, or TCR gamma. In some instances, the intracellular domain is derived from only CD3 epsilon, only CD3 gamma, only CD3 delta, only TCR alpha, only TCR beta, only TCR delta, or only TCR gamma. [0670] In some instances, the TCR subunit comprises (i) at least a portion of a TCR extracellular domain, (ii) a TCR transmembrane domain, and (iii) a TCR intracellular domain, wherein at least two of (i), (ii), and (iii) are from the same TCR subunit. [0671] In some instances, the TCR extracellular domain comprises an extracellular domain or portion thereof of a protein selected from the group consisting of a TCR alpha chain, a TCR beta chain, a TCR delta chain, a TCR gamma chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, a CD3 delta TCR subunit, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0672] In some instances, the TCR subunit comprises a transmembrane domain comprising a transmembrane domain of a protein selected from the group consisting of a TCR alpha chain, a TCR beta chain, a TCR delta chain, a TCR gamma chain, a TCR zeta chain, a CD3 epsilon TCR subunit, a CD3 gamma TCR subunit, a CD3 delta TCR subunit, CD45, CD4, CD5, CD8, CD9, CD16, CD22, CD33, CD28, CD37, CD64, CD80, CD86, CD134, CD137, CD154, functional fragments thereof, and amino acid sequences thereof having at least one but not more than 20 modifications. [0673] In some instances, the TFP, the TCR gamma constant domain, the TCR delta constant domain, the TCR alpha constant domain, the TCR beta constant domain, and any combination thereof is capable of functionally interacting with an endogenous TCR complex and/or at least one endogenous TCR polypeptide. In some instances, (a) the TCR constant domain is a TCR gamma constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR beta, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; (b) the TCR constant domain is a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR gamma, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; (c) the TCR constant domain is a TCR gamma constant domain and a TCR delta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; (d) the TCR constant domain is a TCR alpha constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR beta, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof; or (e) the TCR constant domain is a TCR beta constant domain and the TFP functionally integrates into a TCR complex comprising an endogenous subunit of TCR alpha, CD3 epsilon, CD3 gamma, CD3 delta, or a combination thereof. [0674] In some instances, the at least one but not more than 20 modifications thereto comprise a modification of an amino acid that mediates cell signaling or a modification of an amino acid that is phosphorylated in response to a ligand binding to the TFP. [0675] In some instances, the murine, human or humanized antibody is an antibody fragment. In some instances, the antibody fragment is a scFv, a single domain antibody domain, a VH domain or a VL domain. In some instances, murine, human or humanized antibody comprising an antigen binding domain is selected from a group consisting of an anti-CD19 binding domain, anti-CD20 binding domain, anti-mesothelin binding domain, anti-PMSA binding domain, anti- CD70 binding domain, anti-CD79b binding domain, anti-MUC16 binding domain, anti-anti-B- cell maturation antigen (BCMA) binding domain, anti-mesothelin (MSLN) binding domain, anti- IL13Rα2 binding domain, anti-CD22 binding domain, anti-BAFF or anti-BAFFR binding domain, anti-PD-1 binding domain, anti-PD-L1 binding domain, and anti-ROR-1 binding domain. [0676] In some embodiments, a sequence encoding the antigen binding domain or ligand binding domain is operatively linked to a sequence encoding a delta constant domain. In some embodiments, the intracellular domain is an intracellular domain of TCR gamma. In some embodiments, a sequence encoding the antigen binding domain or ligand binding domain is operatively linked to a sequence encoding a gamma constant domain. In some embodiments, the intracellular domain is an intracellular domain of TCR delta. In some embodiments, a sequence encoding the antigen binding domain or ligand binding domain is operatively linked to both a sequence encoding a TCR delta constant domain or fragment thereof and a TCR gamma constant domain or fragment thereof. In some embodiments, the intracellular signaling domain is CD3 epsilon, CD3 gamma, or CD3 delta. In some embodiments, the intracellular signaling domain is CD3 epsilon. In some embodiments, the recombinant nucleic acid further comprises at least one leader sequence and at least one linker. In some embodiments, the recombinant nucleic acid further comprises a portion of a TCR alpha constant domain, a portion of a TCR beta domain, or both. In some embodiments, the sequence comprises, from 5’ to 3’, a first leader sequence, an antigen binding domain sequence, a linker, a TRDC gene sequence, a cleavable linker sequence, a second leader sequence, and a TRGC gene sequence. In some embodiments, the sequence comprises, from 5’-3’, a first leader sequence, a TRDC gene sequence, a cleavable linker sequence, a second leader sequence, an antigen binding domain sequence, a linker sequence, and a TRGC gene sequence. In some embodiments, the sequence comprises, from 5’-3’, a first leader sequence, an antigen binding domain sequence, a first linker sequence, a TRDC gene sequence, a cleavable linker, a second leader sequence, a second antigen binding domain sequence, a second linker sequence, and a TRGC gene sequence. In some embodiments, the sequence comprises, from 5’-3’, a first leader sequence, a TRDC gene sequence, a first cleavable linker sequence, a second leader sequence, a TRGC gene sequence, a second cleavable linker sequence, a third leader sequence, an antigen binding domain sequence, a linker sequence, and a CD3 epsilon gene sequence. In some embodiments, the sequence comprises, from 5’-3’, a first leader sequence, a first antigen binding domain sequence, a first linker sequence, a TRDC gene sequence or fragment thereof, a TRAC gene sequence or fragment thereof, a cleavable linker sequence, a second leader sequence, a second antigen binding domain sequence, a second linker sequence, a TRGC gene sequence or fragment thereof, and a TRBC gene sequence or fragment thereof. In some embodiments, the binding ligand is capable of binding an Fc domain of the antibody. In some embodiments, the binding ligand is capable of selectively binding an IgG1 antibody. In some embodiments, the binding ligand is capable of specifically binding an IgG4 antibody. In some embodiments, the antibody or fragment thereof binds to a cell surface antigen. In some embodiments, the antibody or fragment thereof is murine, human or humanized. In some embodiments, the antibody or fragment thereof binds to a cell surface antigen on the surface of a tumor cell. In some embodiments, the binding ligand comprises a monomer, a dimer, a trimer, a tetramer, a pentamer, a hexamer, a heptamer, an octomer, a nonamer, or a decamer. In some embodiments, the binding ligand does not comprise an antibody or fragment thereof. In some embodiments, the binding ligand comprises a CD16 polypeptide or fragment thereof. In some embodiments, the binding ligand comprises a CD16-binding polypeptide. In some embodiments, the binding ligand is human or humanized. In some embodiments, the recombinant nucleic acid further comprises a nucleic acid sequence encoding an antibody or fragment thereof capable of being bound by the binding ligand. In some embodiments, the antibody or fragment thereof is capable of being secreted from a cell. [0677] The present disclosure, in some cases, provides a recombinant nucleic acid comprising (a) a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, (2) a transmembrane domain, and (3) an intracellular domain of TCR alpha, TCR beta, TCR gamma, or TCR delta or an intracellular domain comprising a stimulatory domain from an intracellular signaling domain of CD3 epsilon, CD3 gamma, or CD3 delta, and (ii) an antibody comprising an antigen binding domain; and (b) an RNAi agent or the sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, where-in the target protein is a protein associated with alloreactivity; wherein the TCR subunit and the antibody are operatively linked, and wherein the TFP functionally incorporates into a TCR complex when expressed in a modified T cell. In some embodiments, the recombinant nucleic acid further comprises a sequence encoding a TCR constant domain, wherein the TCR constant domain is a TCR gamma constant domain, a TCR delta constant domain, or a TCR gamma constant domain and a TCR delta constant domain. In some embodiment, a modified T cell further comprises a functional disruption of an endogenous TCR. [0678] The present disclosure, in some cases, provides a recombinant nucleic acid comprising (a) a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, (2) a transmembrane domain, and (3) an intracellular domain of TCR alpha, TCR beta, TCR gamma, or TCR delta or an intracellular domain comprising a stimulatory domain from an intracellular signaling domain of CD3 epsilon, CD3 gamma, or CD3 delta, and (ii) a binding ligand or a fragment thereof that is capable of binding to an antibody or fragment thereof; and (b) an RNAi agent or the sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, where-in the target protein is a protein associated with alloreactivity; wherein the TCR subunit and the binding ligand or fragment thereof are operatively linked, and wherein the TFP functionally incorporates into TCR complex when expressed in a modified T cell. In some embodiments, the recombinant nucleic acid further comprises a sequence encoding a TCR constant domain, wherein the TCR constant domain is a TCR gamma constant domain, a TCR delta constant domain, or a TCR gamma constant domain and a TCR delta constant domain. In some embodiment, a modified T cell further comprises a functional disruption of an endogenous TCR. Exemplary Constructs [0679] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence comprising: (i) a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (ii) a CSF2RA signal peptide, a CD19 binder light chain, a Whitlow linker, a CD19 binder heavy chain, an mmTRAC, a GSG- P2A sequence, a CSF2RA signal peptide, a CD19 binder light chain, a Whitlow linker, a CD19 binder heavy chain, an mmTRBC, or any combination thereof; (iii) a CSF2RA signal peptide, an mmTRAC, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (iv) a CSF2RA signal peptide, an MSLN binder, an mmTRAC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an mmTRBC, or any combination thereof; (v) a CSF2RA signal peptide, an mmTRAC PRT, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (vi) a CSF2RA signal peptide, an MSLN binder, an mmTRAC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an mmTRBC, or any combination thereof; (vii) a CSF2RA signal peptide, an mmTRAC, a GSG- T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (viii) a CSF2RA signal peptide, a tEGFR, or any combination thereof; (ix) a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (x) a CSF2RA signal peptide, an MSLN binder, a TRDC, a furin cleavage sequence, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, a TRGC1, or any combination thereof; or (xi) a CSF2RA signal peptide, an MSLN binder, an A3(G4S) linker, a CD3e, or any combination thereof. [0680] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence comprising, from N-terminal to C-terminal,: (i) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (ii) a CSF2RA signal peptide operatively linked to a CD19 binder light chain operatively linked to a Whitlow linker operatively linked to a CD19 binder heavy chain operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to a CD19 binder light chain operatively linked to a Whitlow linker operatively linked to a CD19 binder heavy chain operatively linked to an mmTRBC, or any combination thereof; (iii) a CSF2RA signal peptide operatively linked to an mmTRAC operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (iv) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRBC, or any combination thereof; (v) a CSF2RA signal peptide operatively linked to an mmTRAC PRT operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (vi) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRBC, or any combination thereof; (vii) a CSF2RA signal peptide operatively linked to an mmTRAC operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (viii) a CSF2RA signal peptide operatively linked to a tEGFR, or any combination thereof; (ix) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (x) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to a TRDC operatively linked to a furin cleavage sequence operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to a TRGC1, or any combination thereof; or (xi) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3(G4S) linker operatively linked to a CD3e. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence comprising one or more components listed in Table 2, 3, 4, or 5 or any combination thereof. [0681] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence comprising: (i) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (ii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:85, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:227, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:87, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:85, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:227, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:87, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, or any combination thereof; (iii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (iv) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, or any combination thereof; (v) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (vi) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, or any combination thereof; (vii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (viii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:228, or any combination thereof; (ix) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (x) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:243, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:229, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:21, or any combination thereof; or (xi) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof. [0682] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence comprising, from N-terminal to C-terminal,: (i) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (ii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:85 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:227 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:87 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:85 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:227 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:87 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, or any combination thereof; (iii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (iv) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, or any combination thereof; (v) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (vi) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209, or any combination thereof; (vii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (viii) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:228, or any combination thereof; (ix) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof; (x) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:243 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:229 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:21, or any combination thereof; or (xi) an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:258, or any combination thereof. [0683] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence comprising: (i) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (ii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:85, the sequence of SEQ ID NO:227, the sequence of SEQ ID NO:87, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:85, the sequence of SEQ ID NO:227, the sequence of SEQ ID NO:87, the sequence of SEQ ID NO:209, or any combination thereof; (iii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (iv) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:209, or any combination thereof; (v) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (vi) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:209, or any combination thereof; (vii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (viii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:228, or any combination thereof; (ix) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (x) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:243, the sequence of SEQ ID NO:229, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:21, or any combination thereof; or (xi) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof. [0684] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence comprising from N-terminal to C-terminal: (i) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (ii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:85 operatively linked to the sequence of SEQ ID NO:227 operatively linked to the sequence of SEQ ID NO:87 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:85 operatively linked to the sequence of SEQ ID NO:227 operatively linked to the sequence of SEQ ID NO:87 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (iii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (iv) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (v) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (vi) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (vii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (viii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:228, or any combination thereof; (ix) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (x) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:243 operatively linked to the sequence of SEQ ID NO:229 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:21, or any combination thereof; or (xi) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258. In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising a sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to one or more component amino acid sequences listed in Table 2 or 4. In some embodiments, the recombinant nucleic acid encodes an amino acid sequence comprising one or more component amino acid sequences listed in Table 2 or 4, or any combination thereof. [0685] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises: (i) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:282, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:283, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:289, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:291, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (ii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:293, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:294, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:295, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:296, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:297, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (iii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:299, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:300, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:301, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:302, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:303, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:304, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:307, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:308, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:309, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:310, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (iv) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:312, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:283, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:313, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:314, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:316, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:319, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:321, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (v) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:324, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:325, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:326, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:327, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:328, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (vi) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:336, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:337, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:338, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:339, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:340, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (vii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:344, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:345, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:346, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:347, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:348, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (viii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:350, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:351, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:352, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:353, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:354, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (ix) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:356, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:357, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:358, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:359, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:360, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (x) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:375, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xi) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:377, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:378, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:379, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:380, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:381, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:383, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xiii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:385, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:386, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xiv) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:388, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:389, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:379, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:390, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:381, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:391, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xv) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:393, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:394, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xvi) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:396, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:397, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xvii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:399, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:400, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xviii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:402, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:403, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:404, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xix) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:406, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:407, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:408, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xx) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:410, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:411, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:412, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xxi) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:414, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:415, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:416, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xxii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:418, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:419, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:420, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:423, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:424, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xxiii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:426, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:427, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:428, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:429, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:430, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xxiv) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:432, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:433, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:434, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:435, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:436, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xxv) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:438, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:439, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:440, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:441, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:442, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xxvi) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:444, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:445, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:447, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:448, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; (xxvii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:450, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:451, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:452, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:453, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292;, or any combination thereof (xxviii) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:455, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:456, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:457, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292, or any combination thereof; or (xxix) a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:330, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:331, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:332, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:333, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:334, a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to SEQ ID NO:292., or any combination thereof [0686] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises: (i) the sequence of SEQ ID NO:282, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:283, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:289, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:291, the sequence of SEQ ID NO:292, or any combination thereof; (ii) the sequence of SEQ ID NO:293, the sequence of SEQ ID NO:294, the sequence of SEQ ID NO:295, the sequence of SEQ ID NO:296, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:297, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:292, or any combination thereof; (iii) the sequence of SEQ ID NO:299, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:300, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:301, the sequence of SEQ ID NO:302, the sequence of SEQ ID NO:303, the sequence of SEQ ID NO:304, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:307, the sequence of SEQ ID NO:308, the sequence of SEQ ID NO:309, the sequence of SEQ ID NO:310, the sequence of SEQ ID NO:292, or any combination thereof; (iv) the sequence of SEQ ID NO:312, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:283, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:313, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:314, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:316, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:319, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:321, the sequence of SEQ ID NO:292, or any combination thereof; (v) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:324, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:325, the sequence of SEQ ID NO:326, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:327, the sequence of SEQ ID NO:328, the sequence of SEQ ID NO:292, or any combination thereof; (vi) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:336, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:337, the sequence of SEQ ID NO:338, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:339, the sequence of SEQ ID NO:340, the sequence of SEQ ID NO:292, or any combination thereof; (vii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:344, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:345, the sequence of SEQ ID NO:346, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:347, the sequence of SEQ ID NO:348, the sequence of SEQ ID NO:292, or any combination thereof; (viii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:350, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:351, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:352, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:353, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:354, the sequence of SEQ ID NO:292, or any combination thereof; (ix) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:356, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:357, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:358, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:359, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:360, the sequence of SEQ ID NO:292, or any combination thereof; (x) the sequence of SEQ ID NO:375, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:292, or any combination thereof; (xi) the sequence of SEQ ID NO:377, the sequence of SEQ ID NO:378, the sequence of SEQ ID NO:379, the sequence of SEQ ID NO:380, the sequence of SEQ ID NO:381, the sequence of SEQ ID NO:292, or any combination thereof; (xii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:383, the sequence of SEQ ID NO:292, or any combination thereof; (xiii) the sequence of SEQ ID NO:385, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:386, the sequence of SEQ ID NO:292, or any combination thereof; (xiv) the sequence of SEQ ID NO:388, the sequence of SEQ ID NO:389, the sequence of SEQ ID NO:379, the sequence of SEQ ID NO:390, the sequence of SEQ ID NO:381, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:391, the sequence of SEQ ID NO:292, or any combination thereof; (xv) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:393, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:394, the sequence of SEQ ID NO:292, or any combination thereof; (xvi) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:396, the sequence of SEQ ID NO:397, the sequence of SEQ ID NO:292, or any combination thereof; (xvii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:399, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:400, the sequence of SEQ ID NO:292, or any combination thereof; (xviii) the sequence of SEQ ID NO:402, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:403, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:404, the sequence of SEQ ID NO:292, or any combination thereof; (xix) the sequence of SEQ ID NO:406, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:407, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:408, the sequence of SEQ ID NO:292, or any combination thereof; (xx) the sequence of SEQ ID NO:410, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:411, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:412, the sequence of SEQ ID NO:292, or any combination thereof; (xxi) the sequence of SEQ ID NO:414, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:415, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:416, the sequence of SEQ ID NO:292, or any combination thereof; (xxii) the sequence of SEQ ID NO:418, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:419, the sequence of SEQ ID NO:420, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:423, the sequence of SEQ ID NO:424, the sequence of SEQ ID NO:292, or any combination thereof; (xxiii) the sequence of SEQ ID NO:426, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:427, the sequence of SEQ ID NO:428, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:429, the sequence of SEQ ID NO:430, the sequence of SEQ ID NO:292, or any combination thereof; (xxiv) the sequence of SEQ ID NO:432, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:433, the sequence of SEQ ID NO:434, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:435, the sequence of SEQ ID NO:436, the sequence of SEQ ID NO:292, or any combination thereof; (xxv) the sequence of SEQ ID NO:438, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:439, the sequence of SEQ ID NO:440, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:441, the sequence of SEQ ID NO:442, the sequence of SEQ ID NO:292, or any combination thereof; (xxvi) the sequence of SEQ ID NO:444, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:445, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:447, the sequence of SEQ ID NO:448, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292, or any combination thereof; (xxvii) the sequence of SEQ ID NO:450, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:451, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:452, the sequence of SEQ ID NO:453, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292; or (xxviii) the sequence of SEQ ID NO:455, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:456, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:457, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292, or any combination thereof; or (xxix) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:330, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:331, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:332, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:333, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:334, the sequence of SEQ ID NO:292, or any combination thereof. [0687] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises a nucleic acid sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to one or more component nucleic acid sequence listed in Table 3 or 5. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises one or more component nucleic acid sequence listed in Table 3 or 5. [0688] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes an amino acid sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to any one full amino acid sequence listed in Table 2 or 4. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that encodes any one full amino acid sequence listed in Table 2 or 4. [0689] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:2-15, 65-68, 71, 159, 192-194, 198, 199, and 221-224. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises a sequence selected from the group consisting of SEQ ID NO:2-15, 65-68, 71, 159, 192-194, 198, 199, and 221-224. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to any one full nucleic acid sequence listed in Table 3 or 5. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises any one full nucleic acid sequence listed in Table 3 or 5. [0690] In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:230-241 and 269-281. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises a sequence selected from the group consisting of SEQ ID NO:230- 241 and 269-281. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises a sequence having at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, 99.5%, 99.7%, or 99.9% sequence identity to any one transgene nucleic acid sequence listed in in Table 3 or 5. In some embodiments, the present disclosure provides an exemplary recombinant nucleic acid that comprises any one transgene nucleic acid sequence listed in in Table 3 or 5. Vectors [0691] The present disclosure provides a vector comprising the recombinant nucleic acid molecule encoding the TFP described herein. The vector can comprise an RNAi agent or the sequence encoding the RNAi agent. In one aspect, the vector can be directly transduced into a cell, e.g., a T cell. In one aspect, the vector is a cloning or expression vector, e.g., a vector including, but not limited to, one or more plasmids (e.g., expression plasmids, cloning vectors, minicircles, minivectors, double minute chromosomes), retroviral and lentiviral vector constructs. In one aspect, the vector is capable of expressing the TFP construct and an RNAi agent in mammalian T cells. In one aspect, the mammalian T cell is a human T cell. [0692] In some instances, the vector is selected from the group consisting of a DNA, a RNA, a plasmid, a lentivirus vector, adenoviral vector, an adeno-associated viral vector (AAV), a Rous sarcoma viral (RSV) vector, or a retrovirus vector. In some instances, the vector is an AAV6 vector. In some instances, the vector further comprises a promoter. In some instances, the vector is an in vitro transcribed vector. [0693] The nucleic acid sequences coding for the desired molecules can be obtained using recombinant methods known in the art, such as, for example by screening libraries from cells expressing the gene, by deriving the gene from a vector known to include the same, or by isolating directly from cells and tissues containing the same, using standard techniques. Alternatively, the gene of interest can be produced synthetically, rather than cloned. [0694] The present disclosure also provides vectors in which a DNA of the present disclosure is inserted. Vectors derived from retroviruses such as the lentivirus are suitable tools to achieve long-term gene transfer since they allow long-term, stable integration of a transgene and its propagation in daughter cells. Lentiviral vectors have the added advantage over vectors derived from onco-retroviruses such as murine leukemia viruses in that they can transduce non- proliferating cells, such as hepatocytes. They also have the added advantage of low immunogenicity. [0695] The expression constructs of the present disclosure may also be used for nucleic acid immunization and gene therapy, using standard gene delivery protocols. Methods for gene delivery are known in the art (see, e.g., U.S. Pat. Nos.5,399,346, 5,580,859, 5,589,466, incorporated by reference herein in their entireties). In another embodiment, the present disclosure provides a gene therapy vector. [0696] The nucleic acid can be cloned into a number of types of vectors. For example, the nucleic acid can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, an animal virus, and a cosmid. Vectors of particular interest include expression vectors, replication vectors, probe generation vectors, and sequencing vectors. [0697] Further, the expression vector may be provided to a cell in the form of a viral vector. Viral vector technology is well known in the art and is described, for example, in Sambrook et al., 2012, Molecular Cloning: A Laboratory Manual, volumes 1-4, Cold Spring Harbor Press, NY), and in other virology and molecular biology manuals. Viruses, which are useful as vectors include, but are not limited to, retroviruses, adenoviruses, adeno-associated viruses, herpes viruses, and lentiviruses. In general, a suitable vector contains an origin of replication functional in at least one organism, a promoter sequence, convenient restriction endonuclease sites, and one or more selectable markers, (e.g., WO 01/96584; WO 01/29058; and U.S. Pat. No.6,326,193). [0698] A number of virally based systems have been developed for gene transfer into mammalian cells. For example, retroviruses provide a convenient platform for gene delivery systems. A selected gene can be inserted into a vector and packaged in retroviral particles using techniques known in the art. The recombinant virus can then be isolated and delivered to cells of the subject either in vivo or ex vivo. A number of retroviral systems are known in the art. In some embodiments, adenovirus vectors are used. A number of adenovirus vectors are known in the art. In one embodiment, lentivirus vectors are used. [0699] Additional promoter elements, e.g., enhancers, regulate the frequency of transcriptional initiation. Typically, these are located in the region 30-110 bp upstream of the start site, although a number of promoters have been shown to contain functional elements downstream of the start site as well. The spacing between promoter elements frequently is flexible, so that promoter function is preserved when elements are inverted or moved relative to one another. In the thymidine kinase (tk) promoter, the spacing between promoter elements can be increased to 50 bp apart before activity begins to decline. Depending on the promoter, it appears that individual elements can function either cooperatively or independently to activate transcription. [0700] Methods of introducing and expressing genes into a cell are known in the art. In the context of an expression vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the expression vector can be transferred into a host cell by physical, chemical, or biological means. [0701] Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, and the like. Methods for producing cells comprising vectors and/or exogenous nucleic acids are well-known in the art. See, for example, Sambrook et al., 2012, Molecular Cloning: A Laboratory Manual, volumes 1-4, Cold Spring Harbor Press, NY). A preferred method for the introduction of a polynucleotide into a host cell is calcium phosphate transfection [0702] Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. Viral vectors, and especially retroviral vectors, have become the most widely used method for inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus I, adenoviruses and adeno-associated viruses, and the like (see, e.g., U.S. Pat. Nos.5,350,674 and 5,585,362. [0703] Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle). Other methods of state-of-the-art targeted delivery of nucleic acids are available, such as delivery of polynucleotides with targeted nanoparticles or other suitable sub-micron sized delivery system. [0704] In the case where a non-viral delivery system is utilized, an exemplary delivery vehicle is a liposome. The use of lipid formulations is contemplated for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo). In another aspect, the nucleic acid may be associated with a lipid. The nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. Lipid, lipid/DNA or lipid/expression vector associated compositions are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, as micelles, or with a “collapsed” structure. They may also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances which may be naturally occurring or synthetic lipids. For example, lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes. [0705] Lipids suitable for use can be obtained from commercial sources. For example, dimyristyl phosphatidylcholine (“DMPC”) can be obtained from Sigma, St. Louis, Mo.; dicetyl phosphate (“DCP”) can be obtained from K & K Laboratories (Plainview, N.Y.); cholesterol (“Choi”) can be obtained from Calbiochem-Behring; dimyristyl phosphatidylglycerol (“DMPG”) and other lipids may be obtained from Avanti Polar Lipids, Inc. (Birmingham, Ala.). Stock solutions of lipids in chloroform or chloroform/methanol can be stored at about -20 °C. Chloroform is used as the only solvent since it is more readily evaporated than methanol. “Liposome” is a generic term encompassing a variety of single and multilamellar lipid vehicles formed by the generation of enclosed lipid bilayers or aggregates. Liposomes can be characterized as having vesicular structures with a phospholipid bilayer membrane and an inner aqueous medium. Multilamellar liposomes have multiple lipid layers separated by aqueous medium. They form spontaneously when phospholipids are suspended in an excess of aqueous solution. The lipid components undergo self-rearrangement before the formation of closed structures and entrap water and dissolved solutes between the lipid bilayers (Ghosh et al., 1991 Glycobiology 5: 505-10). However, compositions that have different structures in solution than the normal vesicular structure are also encompassed. For example, the lipids may assume a micellar structure or merely exist as nonuniform aggregates of lipid molecules. Also contemplated are lipofectamine- nucleic acid complexes. [0706] Regardless of the method used to introduce exogenous nucleic acids into a host cell or otherwise expose a cell to the inhibitor of the present disclosure, in order to confirm the presence of the recombinant DNA sequence in the host cell, a variety of assays may be performed. Such assays include, for example, “molecular biological” assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; “biochemical” assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and western blots) or by assays described herein to identify agents falling within the scope of the present disclosure. Genetically-Modified Immune Cells [0707] The present disclosure provides genetically-modified immune cells and populations thereof and methods for producing the same. In some embodiments, the genetically-modified immune cells of the presently disclosed compositions and methods are human immune cells. In some embodiments, the immune cells are T cells, or cells derived therefrom. In other embodiments, the immune cells are natural killer (NK) cells, or cells derived therefrom. In still other embodiments, the immune cells are B cells, or cells derived therefrom. In yet other embodiments, the immune cells are monocyte or macrophage cells or cells derived therefrom. [0708] In some of those embodiments wherein the expression of an endogenous protein is reduced by a shRNAmiR, the expression of the endogenous protein is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell (e.g., a cell not expressing a shRNAmiR). Any method known in the art can be used to determine the expression level of an endogenous protein targeted by a shRNAmiR, including but not limited to, ELISA, flow cytometry, Western blot, immunocytochemistry, and immunoprecipitation. [0709] Expressing a shRNAmiR by cells within a population can lead to a reduction in the percentage of cells in the population of cells that fully express the endogenous protein to which the shRNAmiR is targeted when compared to a population of control cells. Such a reduction may be up to 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99%, or up to 100% of cells in the population. [0710] A nucleic acid sequence encoding a pri-shRNAmiR can be present in the genome of the genetically-modified immune cell, for example, in a cassette. Such cassettes can be inserted into the genome, for example, by introducing a template nucleic acid of the invention either by random integration (e.g., lentiviral transduction) or by targeted insertion into a selected site (e.g., by nuclease-mediated targeted insertion). Cassettes comprising the pri-shRNAmiR-encoding sequence can include, for example, nucleic acid sequences encoding additional proteins, such as a TFP described herein, and may also include control sequences such as promoters and termination sequences. The nucleic acid sequence encoding the pri-shRNAmiR can be positioned at any number of locations within the cassette or template nucleic acid that allow for expression of the pri-shRNAmiR. In some examples, a nucleic acid sequence encoding a pri-shRNAmiR is positioned in the promoter of the nucleic acid sequence encoding a TFP described herein. Here, “positioned” is intended to mean that the intron sequence is inserted into the promoter sequence, such that the resulting sequence comprises a 5' portion of the promoter, the pri-shRNAmiR sequence, and a 3' portion of the promoter sequence. In some examples, a nucleic acid sequence encoding a pri-shRNAmiR is positioned in the 5’ UTR or 3’ UTR of the nucleic acid sequence encoding a TFP described herein. Here, “positioned” is intended to mean that the intron sequence is inserted into the UTR (e.g.5’ or 3’ UTR) sequence, such that the resulting sequence comprises a 5' portion of the UTR (the 5’ or 3’ UTR), the pri-shRNAmiR sequence, and a 3' portion of the UTR (the 5’ or 3’ UTR) sequence. In any of said embodiments, expression of the pri- shRNAmiR is driven by the promoter of the TFP. [0711] In some embodiments, genetically-modified immune cells of the invention comprise an inactivated TCR alpha gene and/or an inactivated TCR beta gene. Inactivation of the TCR alpha gene and/or TCR beta gene to generate the genetically-modified cells of the present disclosure occurs in at least one or both alleles where the TCR alpha gene and/or TCR beta gene is being expressed. Accordingly, inactivation of one or both genes prevents expression of the endogenous TCR alpha chain or the endogenous TCR beta chain protein. Expression of these proteins is required for assembly of the endogenous alpha/beta TCR on the cell surface. Thus, inactivation of the TCR alpha gene and/or the TCR beta gene results in genetically-modified immune that have no detectable cell surface expression of the endogenous alpha/beta TCR. In particular embodiments, the inactivated gene is a TCR alpha constant region (TRAC) gene. [0712] In some examples, the TCR alpha gene, the TRAC gene, or the TCR beta gene is inactivated by insertion of a template nucleic acid into a cleavage site in the gene. Insertion of the template nucleic acid disrupts expression of the endogenous TCR alpha chain or TCR beta chain and, therefore, prevents assembly of an endogenous alpha/beta TCR on the T cell surface. In some examples, the template nucleic acid is inserted into the TRAC gene. [0713] In some of those embodiments wherein the genetically-modified immune cell expresses a TFP, such cells have no detectable cell-surface expression of an endogenous T cell receptor (e.g., an alpha/beta T cell receptor). Thus, the invention further provides a population of genetically- modified immune cells that express a pri-shRNAmiR and have no detectable cell-surface expression of an endogenous T cell receptor (e.g., an alpha/beta T cell receptor), and in some embodiments also express a TFP. For example, the population can include a plurality of genetically-modified immune cells of the invention which express a TFP, and have no cell- surface expression of an endogenous T cell receptor (i.e., are TCR-). [0714] As used herein, “detectable cell-surface expression of an endogenous TCR” refers to the ability to detect one or more components of the TCR complex (e.g., an alpha/beta TCR complex) on the cell surface of an immune cell using standard experimental methods. Such methods can include, for example, immunostaining and/or flow cytometry specific for components of the TCR itself, such as a TCR alpha or TCR beta chain, or for components of the assembled cell- surface TCR complex, such as CD3. Methods for detecting cell-surface expression of an endogenous TCR (e.g., an alpha/beta TCR) on an immune cell include those described in the examples herein, and, for example, those described in MacLeod et al. (2017) Molecular Therapy 25(4): 949-961. [0715] In some cases, the present disclosure provides a modified allogenic immune cell, e.g., T cell comprising the sequence encoding the TFP described herein or a TFP encoded by the sequence of the nucleic acid described herein encoding the TFP and the RNAi agent or the sequence encoding the RNAi agent as described herein. [0716] In some embodiments, the modified allogeneic immune cells comprising the sequence encoding the TFP described herein or a TFP encoded by the sequence of the nucleic acid described herein encoding the TFP and the RNAi agent or the sequence encoding the RNAi agent as described herein exhibit reduced allogenicity compared to a control cells that so not express the RNAi agent or the sequence encoding the RNAi agent as described herein. In some embodiments, the modified allogeneic immune cells that exhibit reduced allogenicity may be used in the cell therapies to provide better treatment for cancer patients. In some embodiments, the modified allogeneic immune cells that exhibit reduced allogenicity may be used in the cell therapies to avoid immune responses associated with allogenicity, such as, for example, Graft Versus Host Disease (GVHD) and modified T cell rejection. In some embodiments, the modified allogeneic immune cells that exhibit reduced allogenicity may be used in the cell therapies to overcome the limitations of the autologous cell therapy, such as, for example, T cell dysfunction, harvest and manufacture failure, and disease progression during manufacture. Modified T cells [0717] Disclosed herein, in some embodiments, are modified immune cells, e.g., T cells comprising the recombinant nucleic acid disclosed herein, or the vectors disclosed herein. In some embodiments, the modified T cell further comprises a functional disruption of an endogenous TCR. Also disclosed herein, in some embodiments, are modified T cells comprising the sequence encoding the TFP of the nucleic acid disclosed herein or a TFP encoded by the sequence of the nucleic acid disclosed herein and an RNAi agent or the sequence encoding the RNAi agent as described herein. In some embodiments, the modified T cell further comprises a functional disruption of an endogenous TCR. Further disclosed herein, in some embodiments, are modified allogenic T cells comprising the sequence encoding the TFP disclosed herein or a TFP encoded by the sequence of the nucleic acid disclosed herein and an RNAi agent or the sequence encoding the RNAi agent as described herein. [0718] Disclosed herein, in some embodiments, are modified T cell comprising the recombinant nucleic acid disclosed above, or the vector disclosed above; wherein the modified T cell further comprises a functional disruption of an endogenous TCR. Further disclosed herein, in some embodiments, are modified T cells comprising the sequence encoding the TFP of the nucleic acid disclosed above or a TFP encoded by the sequence of the nucleic acid disclosed above encoding the TFP and an RNAi agent or the sequence encoding the RNAi agent as described herein, wherein the modified T cell further comprises a functional disruption of an endogenous TCR. Also disclosed herein, are modified allogenic T cell comprising the sequence encoding the TFP disclosed above or a TFP encoded by the sequence of the nucleic acid disclosed above encoding the TFP and an RNAi agent or the sequence encoding the RNAi agent as described herein. In some instances, the T cell further comprises a heterologous sequence encoding a TCR constant domain, wherein the TCR constant domain is a TCR gamma constant domain, a TCR delta constant domain or a TCR gamma constant domain and a TCR delta constant domain. In some instances, the endogenous TCR that is functionally disrupted is an endogenous TCR alpha chain, an endogenous TCR beta chain, or an endogenous TCR alpha chain and an endogenous TCR beta chain. In some instances, the endogenous TCR that is functionally disrupted has reduced binding to MHC-peptide complex compared to that of an unmodified control T cell. In some instances, the functional disruption is a disruption of a gene encoding the endogenous TCR. In some instances, the disruption of a gene encoding the endogenous TCR is a removal of a sequence of the gene encoding the endogenous TCR from the genome of a T cell. In some instances, the T cell is a human T cell. In some instances, the T cell is a CD8+ T cell, a CD4+ T cell, a naïve T cell, a memory stem T cell, a central memory T cell, a double negative T cell, an effector memory T cell, an effector T cell, a ThO cell, a TcO cell, a Th1 cell, a Tc1 cell, a Th2 cell, a Tc2 cell, a Th17 cell, a Th22 cell, a gamma delta T cell, a natural killer (NK) cell, a natural killer T (NKT) cell, a hematopoietic stem cell, or a pluripotent stem cell. In some instances, the T cell is a CD8+ or CD4+ T cell. In some embodiments, the T cell is a CD4+CD8+ T cell. In some instances, the T cell is an allogenic T cell. In some instances, the modified T cells further comprise a nucleic acid encoding an inhibitory molecule that comprises a first polypeptide comprising at least a portion of an inhibitory molecule, associated with a second polypeptide comprising a positive signal from an intracellular signaling domain. In some instances, the inhibitory molecule comprises the first polypeptide comprising at least a portion of PD1 and the second polypeptide comprising a costimulatory domain and primary signaling domain. [0719] In some instances, the T cell further comprises a heterologous sequence encoding a TCR constant domain, wherein the TCR constant domain is a TCR alpha constant domain, a TCR beta constant domain, a TCR alpha constant domain and a TCR beta constant domain, a TCR gamma constant domain, a TCR delta constant domain or a TCR gamma constant domain and a TCR delta constant domain. In some instances, the endogenous TCR that is functionally disrupted is an endogenous TCR alpha chain, an endogenous TCR beta constant domain, an endogenous TCR alpha constant domain and an endogenous TCR beta constant domain, an endogenous TCR gamma chain, an endogenous TCR delta chain, or an endogenous TCR gamma chain and an endogenous TCR delta chain. In some instances, the endogenous TCR that is functionally disrupted has reduced binding to MHC-peptide complex compared to that of an unmodified control T cell. In some instances, the functional disruption is a disruption of a gene encoding the endogenous TCR. In some instances, the disruption of a gene encoding the endogenous TCR is a removal of a sequence of the gene encoding the endogenous TCR from the genome of a T cell. In some instances, the T cell is a human T cell. In some instances, the T cell is a CD8+ or CD4+ T cell. In some instances, the T cell is an allogenic T cell. In some embodiments, the T cell is a CD8+ or CD4+ T cell. In some embodiments, the T cell is a human αβ T cell. In some embodiments, the T cell is a human γδ T cell. In some embodiments, the cell is a human NKT cell. In some embodiments, the cell is an allogeneic cell or an autologous cell. In some embodiments, the T cell is modified to comprise a functional disruption of the TCR. In some embodiments, the modified T cells are γδ T cells and do not comprise a functional disruption of an endogenous TCR. In some embodiments, the γδ T cells are Vδ 1+ Vδ 2- γδ T cells. In some embodiments, the γδ T cells are V 1- V 2+ T cells. In some embodiments, the γδ T cells are Vδ 1- Vδ 2- γδ T cells. [0720] In some instances, the modified T cells further comprise a nucleic acid encoding an inhibitory molecule that comprises a first polypeptide comprising at least a portion of an inhibitory molecule, associated with a second polypeptide comprising a positive signal from an intracellular signaling domain. In some instances, the inhibitory molecule comprises the first polypeptide comprising at least a portion of PD1 and the second polypeptide comprising a costimulatory domain and primary signaling domain. [0721] Disclosed herein, in some embodiments, are recombinant nucleic acid molecules comprising a sequence encoding a TFP and an RNAi agent or a sequence encoding the RNAi agent, and a second nucleic acid sequence encoding an agent that can enhance the activity of a modified T cell expressing the TFP and the RNAi agent. In some embodiments, the second nucleic acid sequence is included in a separate nucleic acid sequence. In some embodiments, the second nucleic acid sequence is included in the same nucleic acid molecule as the recombinant nucleic acid molecules. For example, in one embodiment, the agent that can enhance the activity of a modified T cell can be a PD-1 polypeptide. In these embodiments, the PD-1 polypeptide may be operably linked to the N-terminus of an intracellular domain of a costimulatory polypeptide via the C-terminus of the PD-1 polypeptide. For example, in another embodiment, the agent that can enhance the activity of a modified T cell can be an anti-PD-1 antibody, or antigen binding fragment thereof. In this embodiment, the anti-PD-1 antibody or antigen binding fragment thereof may be operably linked to the N-terminus of an intracellular domain of a costimulatory polypeptide via the C-terminus of the anti-PD-1 antibody, or antigen binding fragment thereof. In some embodiments, the PD-1 polypeptide or anti-PD-1 antibody is linked to the intracellular domain of the costimulatory polypeptide via the transmembrane domain of PD- 1. In some embodiments, the costimulatory polypeptide is selected from the group consisting of OX40, CD2, CD27, CDS, ICAM-1, ICOS (CD278), 4-1BB (CD137), GITR, CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, CD226, FcγRI, FcγRII, and FcγRIII. In some embodiments, the costimulatory peptide is CD28. [0722] Disclosed herein, in some embodiments, are recombinant nucleic acid molecules comprising a sequence encoding a TFP and an RNAi agent or a sequence encoding the RNAi agent, wherein the recombinant nucleic acid molecules further comprising an agent that can enhance the activity of a modified T cell expressing the TFP and the RNAi agent. For example, the agent can be an agent that can inhibit an inhibitory molecule that can decrease the ability of a T cell expressing a TFP and an RNAi agent to mount an immune effector response. In some embodiments, the agent which inhibits an inhibitory molecule comprises a first polypeptide, e.g., an inhibitory molecule, associated with a second polypeptide that provides a positive signal to the cell, e.g., an intracellular signaling domain described herein. In one embodiment, the agent may comprise a first polypeptide, e.g., of an inhibitory molecule such as PD-1, LAG3, CTLA4, CD160, BTLA, LAIR1, TIM3, 2B4, and TIGIT, or a fragment of any of these (e.g., at least a portion of an extracellular domain of any of these), and a second polypeptide which is an intracellular signaling domain described herein (e.g., comprising a costimulatory domain (e.g., 4- 1BB, CD27, or CD28, as described herein)) and/or a primary signaling domain. In some embodiments, the recombinant nucleic acid molecules as described herein further comprises a sequence encoding PD-1 or a fragment thereof. In some embodiments, the recombinant nucleic acid molecules as described herein further comprises a sequence encoding the extracellular domain of PD-1. In some embodiments, the recombinant nucleic acid molecules as described herein comprises a sequence encoding the extracellular domain and transmembrane domain of PD-1. In some embodiments, the recombinant nucleic acid molecules as described herein may further comprise a sequence encoding CD28 or a fragment thereof. In some embodiments, the recombinant nucleic acid molecules as described herein comprises a sequence encoding the intracellular domain of CD28. In some embodiments, the recombinant nucleic acid molecules as described herein comprises a sequence encoding a fusion protein comprising the PD-1 extracellular domain and transmembrane domain linked to the CD28 intracellular domain linked to intracellular domain. Sources of T cells [0723] Prior to expansion and genetic modification, a source of T cells is obtained from a subject. The term “subject” is intended to include living organisms in which an immune response can be elicited (e.g., mammals). Examples of subjects include humans, dogs, cats, mice, rats, and transgenic species thereof. T cells can be obtained from a number of sources, including peripheral blood mononuclear cells, bone marrow, lymph node tissue, cord blood, thymus tissue, tissue from a site of infection, ascites, pleural effusion, spleen tissue, and tumors. In certain aspects of the present disclosure, any number of T cell lines available in the art, may be used. In certain aspects of the present disclosure, T cells can be obtained from a unit of blood collected from a subject using any number of techniques known to the skilled artisan, such as FicollTM separation. In one preferred aspect, cells from the circulating blood of an individual are obtained by apheresis. The apheresis product typically contains lymphocytes, including T cells, monocytes, granulocytes, B cells, other nucleated white blood cells, red blood cells, and platelets. In one aspect, the cells collected by apheresis may be washed to remove the plasma fraction and to place the cells in an appropriate buffer or media for subsequent processing steps. In one aspect of the present disclosure, the cells are washed with phosphate buffered saline (PBS). In an alternative aspect, the wash solution lacks calcium and may lack magnesium or may lack many if not all divalent cations. Initial activation steps in the absence of calcium can lead to magnified activation. As those of ordinary skill in the art would readily appreciate a washing step may be accomplished by methods known to those in the art, such as by using a semi-automated “flow-through” centrifuge (for example, the Cobe® 2991 cell processor, the Baxter Oncology CytoMate™, or the Haemonetics® Cell Saver® 5) according to the manufacturer’s instructions. After washing, the cells may be resuspended in a variety of biocompatible buffers, such as, for example, Ca-free, Mg-free PBS, PlasmaLyte A, or other saline solution with or without buffer. Alternatively, the undesirable components of the apheresis sample may be removed, and the cells directly resuspended in culture media. [0724] In one aspect, T cells are isolated from peripheral blood lymphocytes by lysing the red blood cells and depleting the monocytes, for example, by centrifugation through a PERCOLL®gradient or by counterflow centrifugal elutriation. A specific subpopulation of T cells, such as CD3+, CD28+, CD4+, CD8+, CD45RA+, and CD45RO+ T cells, can be further isolated by positive or negative selection techniques. For example, in one aspect, T cells are isolated by incubation with anti-CD3/anti-CD28 (e.g., 3x28)-conjugated beads, such as DYNABEADS® M-450 CD3/CD28 T, for a time period sufficient for positive selection of the desired T cells. In one aspect, the time period is about 30 minutes. In a further aspect, the time period ranges from 30 minutes to 36 hours or longer and all integer values there between. In a further aspect, the time period is at least 1, 2, 3, 4, 5, or 6 hours. In yet another preferred aspect, the time period is 10 to 24 hours. In one aspect, the incubation time period is 24 hours. Longer incubation times may be used to isolate T cells in any situation where there are few T cells as compared to other cell types, such in isolating tumor infiltrating lymphocytes (TIL) from tumor tissue or from immunocompromised individuals. Further, use of longer incubation times can increase the efficiency of capture of CD8+ T cells. Thus, by simply shortening or lengthening the time T cells are allowed to bind to the CD3/CD28 beads and/or by increasing or decreasing the ratio of beads to T cells (as described further herein), subpopulations of T cells can be preferentially selected for or against at culture initiation or at other time points during the process. Additionally, by increasing or decreasing the ratio of anti-CD3 and/or anti-CD28 antibodies on the beads or other surface, subpopulations of T cells can be preferentially selected for or against at culture initiation or at other desired time points. The skilled artisan would recognize that multiple rounds of selection can also be used in the context of this present disclosure. In certain aspects, it may be desirable to perform the selection procedure and use the “unselected” cells in the activation and expansion process. “Unselected” cells can also be subjected to further rounds of selection. [0725] Enrichment of a T cell population by negative selection can be accomplished with a combination of antibodies directed to surface markers unique to the negatively selected cells. One method is cell sorting and/or selection via negative magnetic immunoadherence or flow cytometry that uses a cocktail of monoclonal antibodies directed to cell surface markers present on the cells negatively selected. For example, to enrich for CD4+ cells by negative selection, a monoclonal antibody cocktail typically includes antibodies to CD14, CD20, CD11b, CD16, HLA-DR, and CD8. In certain aspects, it may be desirable to enrich for or positively select for regulatory T cells which typically express CD4+, CD25+, CD62Lhi, GITR+, and FoxP3+. Alternatively, in certain aspects, T regulatory cells are depleted by anti-C25 conjugated beads or other similar method of selection. [0726] In one embodiment, a T cell population can be selected that expresses one or more of IFN-γ TNF-alpha, IL-17A, IL-2, IL-3, IL-4, GM-CSF, IL-10, IL-13, granzyme B, and perforin, or other appropriate molecules, e.g., other cytokines. Methods for screening for cell expression can be determined, e.g., by the methods described in PCT Publication No.: WO 2013/126712. [0727] For isolation of a desired population of cells by positive or negative selection, the concentration of cells and surface (e.g., particles such as beads) can be varied. In certain aspects, it may be desirable to significantly decrease the volume in which beads and cells are mixed together (e.g., increase the concentration of cells), to ensure maximum contact of cells and beads. For example, in one aspect, a concentration of 2 billion cells/mL is used. In one aspect, a concentration of 1 billion cells/mL is used. In a further aspect, greater than 100 million cells/mL is used. In a further aspect, a concentration of cells of 10, 15, 20, 25, 30, 35, 40, 45, or 50 million cells/mL is used. In yet one aspect, a concentration of cells from 75, 80, 85, 90, 95, or 100 million cells/mL is used. In further aspects, concentrations of 125 or 150 million cells/mL can be used. Using high concentrations can result in increased cell yield, cell activation, and cell expansion. Further, use of high cell concentrations allows more efficient capture of cells that may weakly express target antigens of interest, such as CD28-negative T cells, or from samples where there are many tumor cells present (e.g., leukemic blood, tumor tissue, etc.). Such populations of cells may have therapeutic value and would be desirable to obtain. For example, using high concentration of cells allows more efficient selection of CD8+ T cells that normally have weaker CD28 expression. [0728] In a related aspect, it may be desirable to use lower concentrations of cells. By significantly diluting the mixture of T cells and surface (e.g., particles such as beads), interactions between the particles and cells is minimized. This selects for cells that express high amounts of desired antigens to be bound to the particles. For example, CD4+ T cells express higher levels of CD28 and are more efficiently captured than CD8+ T cells in dilute concentrations. In one aspect, the concentration of cells used is 5x106/mL. In other aspects, the concentration used can be from about 1x105/mL to 1x106/mL, and any integer value in between. In other aspects, the cells may be incubated on a rotator for varying lengths of time at varying speeds at either 2-10 °C or at room temperature. [0729] T cells for stimulation can also be frozen after a washing step. Wishing not to be bound by theory, the freeze and subsequent thaw step provides a more uniform product by removing granulocytes and to some extent monocytes in the cell population. After the washing step that removes plasma and platelets, the cells may be suspended in a freezing solution. While many freezing solutions and parameters are known in the art and will be useful in this context, one method involves using PBS containing 20% DMSO and 8% human serum albumin, or culture media containing 10% Dextran 40 and 5% Dextrose, 20% Human Serum Albumin and 7.5% DMSO, or 31.25% Plasmalyte-A, 31.25% Dextrose 5%, 0.45% NaCl, 10% Dextran 40 and 5% Dextrose, 20% Human Serum Albumin, and 7.5% DMSO or other suitable cell freezing media containing for example, Hespan and PlasmaLyte A, the cells then are frozen to -80 °C at a rate of 1 per minute and stored in the vapor phase of a liquid nitrogen storage tank. Other methods of controlled freezing may be used as well as uncontrolled freezing immediately at -20 °C or in liquid nitrogen. In certain aspects, cryopreserved cells are thawed and washed as described herein and allowed to rest for one hour at room temperature prior to activation using the methods of the present disclosure. [0730] Also contemplated in the context of the present disclosure is the collection of blood samples or apheresis product from a subject at a time period prior to when the expanded cells as described herein might be needed. As such, the source of the cells to be expanded can be collected at any time point necessary, and desired cells, such as T cells, isolated and frozen for later use in T cell therapy for any number of diseases or conditions that would benefit from T cell therapy, such as those described herein. In one aspect a blood sample or an apheresis is taken from a generally healthy subject. In certain aspects, a blood sample or an apheresis is taken from a generally healthy subject who is at risk of developing a disease, but who has not yet developed a disease, and the cells of interest are isolated and frozen for later use. In certain aspects, the T cells may be expanded, frozen, and used at a later time. In certain aspects, samples are collected from a patient shortly after diagnosis of a particular disease as described herein but prior to any treatments. In a further aspect, the cells are isolated from a blood sample or an apheresis from a subject prior to any number of relevant treatment modalities, including but not limited to treatment with agents such as natalizumab, efalizumab, antiviral agents, chemotherapy, radiation, immunosuppressive agents such as cyclosporin, azathioprine, methotrexate, and mycophenolate, antibodies, or other immunoablative agents such as alemtuzumab, anti-CD3 antibodies, cytoxan, fludarabine, cyclosporin, tacrolimus, rapamycin, mycophenolic acid, steroids, romidepsin, and irradiation. [0731] In a further aspect of the present disclosure, T cells are obtained from a patient directly following treatment that leaves the subject with functional T cells. In this regard, it has been observed that following certain cancer treatments, in particular treatments with drugs that damage the immune system, shortly after treatment during the period when patients would normally be recovering from the treatment, the quality of T cells obtained may be optimal or improved for their ability to expand ex vivo. Likewise, following ex vivo manipulation using the methods described herein, these cells may be in a preferred state for enhanced engraftment and in vivo expansion. Thus, it is contemplated within the context of the present disclosure to collect blood cells, including T cells, dendritic cells, or other cells of the hematopoietic lineage, during this recovery phase. Further, in certain aspects, mobilization (for example, mobilization with GM-CSF) and conditioning regimens can be used to create a condition in a subject wherein repopulation, recirculation, regeneration, and/or expansion of particular cell types is favored, especially during a defined window of time following therapy. Illustrative cell types include T cells, B cells, dendritic cells, and other cells of the immune system. Activation and Expansion of T Cells [0732] T cells may be activated and expanded generally using methods as described, for example, in U.S. Pat. Nos.6,352,694; 6,534,055; 6,905,680; 6,692,964; 5,858,358; 6,887,466; 6,905,681; 7,144,575; 7,067,318; 7,172,869; 7,232,566; 7,175,843; 5,883,223; 6,905,874; 6,797,514; 6,867,041; and 7,572,631. [0733] Generally, the T cells of the present disclosure may be expanded by contact with a surface having attached thereto an agent that stimulates a CD3/TCR complex associated signal and a ligand that stimulates a costimulatory molecule on the surface of the T cells. In particular, T cell populations may be stimulated as described herein, such as by contact with an anti-CD3 antibody, or antigen-binding fragment thereof, or an anti-CD2 antibody immobilized on a surface, or by contact with a protein kinase C activator (e.g., bryostatin) in conjunction with a calcium ionophore. For co-stimulation of an accessory molecule on the surface of the T cells, a ligand that binds the accessory molecule is used. For example, a population of T cells can be contacted with an anti-CD3 antibody and an anti-CD28 antibody, under conditions appropriate for stimulating proliferation of the T cells. To stimulate proliferation of either CD4+ T cells or CD8+ T cells, an anti-CD3 antibody and an anti-CD28 antibody. Examples of an anti-CD28 antibody include 9.3, B-T3, XR-CD28 (Diaclone, Besancon, France) can be used as can other methods commonly known in the art (Berg et al., Transplant Proc.30(8):3975-3977, 1998; Haanen et al., J. Exp. Med.190(9):13191328, 1999; Garland et al., J. Immunol. Meth.227(1- 2):53-63, 1999). T cells may additionally be activated and expanded in the presence of a cytokine with or without an anti-CD3 and/or CD28 antibody. Exemplary cytokines include IL-2, IL-7, IL-15, and IL-21. In some embodiments, T cells are activated by incubation with anti- CD3/anti-CD28-conjugated beads, such as DYNABEADS® or Trans-Act® beads, for a time period sufficient for activation of the T cells. In one aspect, the time period is at least 1, 2, 3, 4, 5, or 6 hours. In yet another preferred aspect, the time period is 10 to 24 hours, e.g., 24 hours. In some embodiments, T cells are activated by stimulation with an anti-CD3 antibody and an anti- CD28 antibody in combination with cytokines that bind the common gamma-chain (e.g., IL-2, IL-7, IL-12, IL-15, IL-21, and others). In some embodiments, T cells are activated by stimulation with an anti-CD3 antibody and an anti-CD28 antibody in combination with 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 200, 300, 400, 500, 600, 700, 800, 900, or 100 U/mL of IL-2, IL-7, and/or IL-15. In some embodiments, the cells are activated for 24 hours. In some embodiments, after transduction, the cells are expanded in the presence of anti-CD3 antibody, anti-CD28 antibody in combination with the same cytokines. In some embodiments, cells activated in the presence of an anti-CD3 antibody and an anti-CD28 antibody in combination with cytokines that bind the common gamma-chain are expanded in the presence of the same cytokines in the absence of the anti-CD3 antibody and anti-CD28 antibody after transduction. In some embodiments, after transduction, the cells are expanded in the presence of anti-CD3 antibody, anti-CD28 antibody in combination with the same cytokines up to a first washing step, when the cells are sub-cultured in media that includes the cytokines but does not include the anti-CD3 antibody and anti-CD28 antibody. In some embodiments, the cells are subcultured every 1, 2, 3, 4, 5, or 6 days. In some embodiments, cells are expanded for 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 days. [0734] The expansion of T cells may be stimulated with zoledronic acid (Zometa), alendronic acid (Fosamax) or other related bisphosphonate drugs at concentrations of 0.1, 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 7.5, 10, or 100 µM in the presence of feeder cells (irradiated cancer cells, PBMCs, artificial antigen presenting cells). The expansion of T cells may be stimulated with isopentyl pyrophosphate (IPP), (E)-4-Hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP or HMB-PP) or other structurutally related compounds at concentrations of 0.1, 0.25, 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 7.5, 10, or 100 µM in the presence of feeder cells (irradiated cancer cells, PBMCs, artificial antigen presenting cells). In some embodiments, the expansion of T cells may be stimulated with synthetic phosphoantigens (e.g., bromohydrin pyrophosphate; BrHPP), 2M3B1 PP, or 2-methyl- 3-butenyl-1 -pyrophosphate in the presence of IL-2 for one-to-two weeks. In some embodiments, the expansion of T cells may be stimulated with immobilized anti-TCRyd (e.g., pan TCRY6) in the presence of IL-2, e.g., for approximately 14 days. In some embodiments, the expansion of T cells may be stimulated with culture of immobilized anti-CD3 antibodies (e.g., OKT3) in the presence of IL-2. In some embodiments, the aforementioned culture is maintained for about seven days prior to subculture in soluble anti-CD3, and IL-2. [0735] T cells that have been exposed to varied stimulation times may exhibit different characteristics. For example, typical blood or apheresed peripheral blood mononuclear cell products have a helper T cell population (TH, CD4+) that is greater than the cytotoxic or suppressor T cell population (TC, CD8+). Ex vivo expansion of T cells by stimulating CD3 and CD28 receptors produces a population of T cells that prior to about days 8-9 consists predominately of TH cells, while after about days 8-9, the population of T cells comprises an increasingly greater population of TC cells. Accordingly, depending on the purpose of treatment, infusing a subject with a T cell population comprising predominately of TH cells may be advantageous. Similarly, if an antigen-specific subset of TC cells has been isolated it may be beneficial to expand this subset to a greater degree. [0736] Further, in addition to CD4 and CD8 markers, other phenotypic markers vary significantly, but in large part, reproducibly during the course of the cell expansion process. Thus, such reproducibility enables the ability to tailor an activated T cell product for specific purposes. [0737] Once an anti-CD19 anti-BCMA, anti-CD22, anti-ROR1, anti-PD-1, or anti-BAFF, anti- MUC16, anti-mesothelin, anti-PMSA, anti-CD20, anti-CD70, anti-GPC3, anti-Nectin-4, anti- Trop2, or antiCD79b TFP is constructed, various assays can be used to evaluate the activity of the molecule, such as but not limited to, the ability to expand T cells following antigen stimulation, sustain T cell expansion in the absence of re-stimulation, and anti-cancer activities in appropriate in vitro and animal models. Assays to evaluate the effects of an anti-CD19 anti- BCMA, anti-GPC3, anti-Nectin-4, anti-Trop2, anti-CD22, anti-MSLN, anti-CD79B, anti-ROR1, anti-PD-1, anti-IL13Ra2, anti-PD-L1, anti-CD20, anti-CD70, or anti-BAFF or BAFFR TFP are described in further detail below. [0738] Western blot analysis of TFP expression in primary T cells can be used to detect the presence of monomers and dimers (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). Very briefly, T cells (1:1 mixture of CD4+ and CD8+ T cells) expressing the TFPs are expanded in vitro for more than 10 days followed by lysis and SDS-PAGE under reducing conditions. TFPs are detected by western blotting using an antibody to a TCR chain. The same T cell subsets are used for SDS-PAGE analysis under non-reducing conditions to permit evaluation of covalent dimer formation. [0739] In vitro expansion of TFP+ T cells following antigen stimulation can be measured by flow cytometry. For example, a mixture of CD4+ and CD8+ T cells are stimulated with alphaCD3/alphaCD28 and APCs followed by transduction with lentiviral vectors expressing GFP under the control of the promoters to be analyzed. Exemplary promoters include the CMV IE gene, EF-1alpha, ubiquitin C, or phosphoglycerokinase (PGK) promoters. GFP fluorescence is evaluated on day 6 of culture in the CD4+ and/or CD8+ T cell subsets by flow cytometry (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). Alternatively, a mixture of CD4+ and CD8+ T cells are stimulated with alphaCD3/alphaCD28 coated magnetic beads on day 0, and transduced with TFP on day 1 using a bicistronic lentiviral vector expressing a TFP along with eGFP using a 2A ribosomal skipping sequence. Cultures are re-stimulated with either TAA+ K562 cells (K562-TAA), wild-type K562 cells (K562 wild type) or K562 cells expressing hCD32 and 4-1BBL in the presence of anti-CD3 and anti-CD28 antibody (K562-BBL-3/28) following washing. Exogenous IL-2 is added to the cultures every other day at 100 IU/mL. GFP+ T cells are enumerated by flow cytometry using bead-based counting (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). [0740] Sustained TFP+ T cell expansion in the absence of re-stimulation can also be measured (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). Briefly, mean T cell volume (fl) is measured on day 8 of culture using a Coulter Multisizer III particle counter following stimulation with alphaCD3/alphaCD28 coated magnetic beads on day 0, and transduction with the indicated TFP on day 1. [0741] Animal models can also be used to measure a TFP-T activity. For example, xenograft model using, e.g., human CD19-specific TFP+ T cells to treat a primary human pre-B ALL in immunodeficient mice can be used (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). After establishment of ALL, mice are randomized as to treatment groups. Different numbers of engineered T cells are coinjected at a 1:1 ratio into NOD/SCID/γ-/- mice bearing B- ALL. The number of copies of each vector in spleen DNA from mice is evaluated at various times following T cell injection. Animals are assessed for leukemia at weekly intervals. Peripheral blood CD19+ B-ALL blast cell counts are measured in mice that are injected with alphaCD19-zeta TFP+ T cells or mock-transduced T cells. Survival curves for the groups are compared using the log-rank test. In addition, absolute peripheral blood CD4+ and CD8+ T cell counts 4 weeks following T cell injection in NOD/SCID/γ-/- mice can also be analyzed. Mice are injected with leukemic cells and 3 weeks later are injected with T cells engineered to express TFP by a bicistronic lentiviral vector that encodes the TFP linked to eGFP. T cells are normalized to 45-50% input GFP+ T cells by mixing with mock-transduced cells prior to injection, and confirmed by flow cytometry. Animals are assessed for leukemia at 1-week intervals. Survival curves for the TFP+ T cell groups are compared using the log-rank test. [0742] Dose dependent TFP treatment response can be evaluated (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). For example, peripheral blood is obtained 35-70 days after establishing leukemia in mice injected on day 21 with TFP T cells, an equivalent number of mock-transduced T cells, or no T cells. Mice from each group are randomly bled for determination of peripheral blood CD19+ ALL blast counts and then killed on days 35 and 49. The remaining animals are evaluated on days 57 and 70. [0743] Assessment of cell proliferation and cytokine production has been previously described, e.g., at Milone et al., Molecular Therapy 17(8): 1453-1464 (2009). Briefly, assessment of TFP- mediated proliferation is performed in microtiter plates by mixing washed T cells with K562 cells expressing the tumor associated antigen (TAA, e.g., CD19) CD19 (K19) or CD32 and CD137 (KT32-BBL) for a final T cell:K562 ratio of 2:1. K562 cells are irradiated with gamma- radiation prior to use. Anti-CD3 (clone OKT3) and anti-CD28 (clone 9.3) monoclonal antibodies are added to cultures with KT32-BBL cells to serve as a positive control for stimulating T cell proliferation since these signals support long-term CD8+ T cell expansion ex vivo. T cells are enumerated in cultures using CountBrightTM fluorescent beads (Invitrogen) and flow cytometry as described by the manufacturer. TFP+ T cells are identified by GFP expression using T cells that are engineered with eGFP-2A linked TFP-expressing lentiviral vectors. For TFP+ T cells not expressing GFP, the TFP+ T cells are detected with biotinylated recombinant CD19 protein and a secondary avidin-PE conjugate. CD4+ and CD8+ expression on T cells are also simultaneously detected with specific monoclonal antibodies (BD Biosciences). Cytokine measurements are performed on supernatants collected 24 hours following re-stimulation using the human TH1/TH2 cytokine cytometric bead array kit (BD Biosciences) according the manufacturer's instructions. Fluorescence is assessed using a FACScalibur™ flow cytometer (BD Biosciences), and data are analyzed according to the manufacturer's instructions. [0744] Cytotoxicity can be assessed by a standard 51Cr-release assay (see, e.g., Milone et al., Molecular Therapy 17(8): 1453-1464 (2009)). Target cells (K562 lines and primary pro-B-ALL cells) are loaded with 51Cr (as NaCrO4, New England Nuclear) at 37 °C for 2 hours with frequent agitation, washed twice in complete RPMI and plated into microtiter plates. Effector T cells are mixed with target cells in the wells in complete RPMI at varying ratios of effector cell:target cell (E:T). Additional wells containing media only (spontaneous release, SR) or a 1% solution of Triton-X 100 detergent (total release, TR) are also prepared. After 4 hours of incubation at 37 °C, supernatant from each well is harvested. Released 51Cr is then measured using a gamma particle counter (Packard Instrument Co., Waltham, Mass.). Each condition is performed in at least triplicate, and the percentage of lysis is calculated using the formula: % Lysis=(ER- SR)/(TR-SR), where ER represents the average 51Cr released for each experimental condition. [0745] Imaging technologies can be used to evaluate specific trafficking and proliferation of TFPs in tumor-bearing animal models. Such assays have been described, e.g., in Barrett et al., Human Gene Therapy 22:1575-1586 (2011). NOD/SCID/γc-/- (NSG) mice are injected IV with Nalm-6 cells (ATCC® CRL-3273™) followed 7 days later with T cells 4 hour after electroporation with the TFP constructs. The T cells are stably transfected with a lentiviral construct to express firefly luciferase, and mice are imaged for bioluminescence. Alternatively, therapeutic efficacy and specificity of a single injection of TFP+ T cells in Nalm-6 xenograft model can be measured as the following: NSG mice are injected with Nalm-6 transduced to stably express firefly luciferase, followed by a single tail-vein injection of T cells electroporated with a TAA-TFP 7 days later. Animals are imaged at various time points post injection. For example, photon-density heat maps of firefly luciferase positive leukemia in representative mice at day 5 (2 days before treatment) and day 8 (24 hours post TFP+ PBLs) can be generated. [0746] Other assays, including those described in the Example section herein as well as those that are known in the art can also be used to evaluate the anti-CD19, anti-BCMA, , anti-CD22, anti-MSLN, anti-CD79B, anti-GPC3, anti-Nectin-4, anti-Trop2, anti-IL13Ra2, anti-PD-1, anti- ROR1, anti-PD-L1, or anti-BAFF or BAFFR TFP constructs disclosed herein. Pharmaceutical Compositions [0747] Disclosed herein, in some embodiments, are pharmaceutical compositions comprising: (a) the modified T cells of the disclosure; and (b) a pharmaceutically acceptable carrier. Such compositions may comprise buffers such as neutral buffered saline, phosphate buffered saline and the like; carbohydrates such as glucose, mannose, sucrose or dextrans, mannitol; proteins; polypeptides or amino acids such as glycine; antioxidants; chelating agents such as EDTA or glutathione; adjuvants (e.g., aluminum hydroxide); and preservatives. Compositions of the present disclosure are in one aspect formulated for intravenous administration. [0748] Pharmaceutical compositions of the present disclosure may be administered in a manner appropriate to the disease to be treated (or prevented). The quantity and frequency of administration will be determined by such factors as the condition of the patient, and the type and severity of the patient's disease, although appropriate dosages may be determined by clinical trials. [0749] In one embodiment, the pharmaceutical composition is substantially free of, e.g., there are no detectable levels of a contaminant, e.g., selected from the group consisting of endotoxin, mycoplasma, replication competent lentivirus (RCL), p24, VSV-G nucleic acid, HIV gag, residual anti-CD3/anti-CD28 coated beads, mouse antibodies, pooled human serum, bovine serum albumin, bovine serum, culture media components, vector packaging cell or plasmid components, a bacterium and a fungus. In one embodiment, the bacterium is at least one selected from the group consisting of Alcaligenes faecalis, Candida albicans, Escherichia coli, Haemophilus influenza, Neisseria meningitides, Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumonia, and Streptococcus pyogenes group A. [0750] When “an immunologically effective amount,” “an anti-tumor effective amount,” “a tumor-inhibiting effective amount,” or “therapeutic amount” is indicated, the precise amount of the compositions of the present disclosure to be administered can be determined by a physician with consideration of individual differences in age, weight, tumor size, extent of infection or metastasis, and condition of the patient (subject). It can generally be stated that a pharmaceutical composition comprising the T cells described herein may be administered at a dosage of 104 to 109 cells/kg body weight, in some instances 105 to 106 cells/kg body weight, including all integer values within those ranges. T cell compositions may also be administered multiple times at these dosages. The cells can be administered by using infusion techniques that are commonly known in immunotherapy (see, e.g., Rosenberg et al., New Eng. J. Med.319:1676, 1988). [0751] In certain aspects, it may be desired to administer activated T cells to a subject and then subsequently redraw blood (or have an apheresis performed), activate T cells therefrom according to the present disclosure, and reinfuse the patient with these activated and expanded T cells. This process can be carried out multiple times every few weeks. In certain aspects, T cells can be activated from blood draws of from 10 cc to 400 cc. In certain aspects, T cells are activated from blood draws of 20 cc, 30 cc, 40 cc, 50 cc, 60 cc, 70 cc, 80 cc, 90 cc, or 100 cc. [0752] The administration of the subject compositions may be carried out in any convenient manner, including by aerosol inhalation, injection, ingestion, transfusion, implantation or transplantation. The compositions described herein may be administered to a patient trans arterially, subcutaneously, intradermally, intratumorally, intranodally, intramedullary, intramuscularly, by intravenous (i.v.) injection, or intraperitoneally. In one aspect, the T cell compositions of the present disclosure are administered to a patient by intradermal or subcutaneous injection. In one aspect, the T cell compositions of the present disclosure are administered by i.v. injection. The compositions of T cells may be injected directly into a tumor, lymph node, or site of infection. [0753] In a particular exemplary aspect, subjects may undergo leukapheresis, wherein leukocytes are collected, enriched, or depleted ex vivo to select and/or isolate the cells of interest, e.g., T cells. These T cell isolates may be expanded by methods known in the art and treated such that one or more TFP constructs of the present disclosure may be introduced, thereby creating a modified T-T cell of the present disclosure. Subjects in need thereof may subsequently undergo standard treatment with high dose chemotherapy followed by peripheral blood stem cell transplantation. In certain aspects, following or concurrent with the transplant, subjects receive an infusion of the expanded modified T cells of the present disclosure. In an additional aspect, expanded cells are administered before or following surgery. [0754] The dosage of the above treatments to be administered to a patient will vary with the precise nature of the condition being treated and the recipient of the treatment. The scaling of dosages for human administration can be performed according to art-accepted practices. The dose for alemtuzumab, for example, will generally be in the range 1 to about 100 mg for an adult patient, usually administered daily for a period between 1 and 30 days. The preferred daily dose is 1 to 10 mg per day although in some instances larger doses of up to 40 mg per day may be used (described in U.S. Pat. No.6,120,766). [0755] In one embodiment, the TFP, the RNAi agent or the sequence encoding the RNAi agent as described herein, or a combination thereof is introduced into immune, e.g., T, cells, e.g., using in vitro transcription, and the subject (e.g., human) receives an initial administration of the modified immune cells of the present disclosure, and one or more subsequent administrations of the modified immune cells of the present disclosure, wherein the one or more subsequent administrations are administered less than 15 days, e.g., 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, or 2 days after the previous administration. In one embodiment, more than one administration of the modified immune cells of the present disclosure are administered to the subject (e.g., human) per week, e.g., 2, 3, or 4 administrations of the modified immune cells of the present disclosure are administered per week. In one embodiment, the subject (e.g., human subject) receives more than one administration of the modified immune cells per week (e.g., 2, 3 or 4 administrations per week) (also referred to herein as a cycle), followed by a week of no modified T cells administrations, and then one or more additional administration of the modified immune cells (e.g., more than one administration of the modified immune cells per week) is administered to the subject. In another embodiment, the subject (e.g., human subject) receives more than one cycle of modified immune cells, and the time between each cycle is less than 10, 9, 8, 7, 6, 5, 4, or 3 days. In one embodiment, the modified immune cells are administered every other day for 3 administrations per week. In one embodiment, the modified immune cells of the present disclosure are administered for at least two, three, four, five, six, seven, eight or more weeks. [0756] In one aspect, modified immune cells comprising TFP and the RNAi agent or the sequence encoding the RNAi agent as described herein are generated using lentiviral viral vectors, such as lentivirus. Modified immune cells generated that way will have stable TFP expression and the RNAi agent expression. [0757] In one aspect, modified immune cells transiently express vectors comprising the recombinant nucleic acid comprising a sequence encoding a TFP and an RNAi agent or a sequence encoding the RNAi agent as described herein for 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 days after transduction. Transient expression of TFPs and RNAi agents as described herein can be affected by RNA vector delivery. In one aspect, the TFP RNA and the RNAi agent as described herein is transduced into the T cell by electroporation. [0758] A potential issue that can arise in patients being treated using transiently expressing the modified immune cells (particularly immune cells with murine scFv bearing TFP and the RNAi agent as described herein) is anaphylaxis after multiple treatments. [0759] Without being bound by this theory, it is believed that such an anaphylactic response might be caused by a patient developing humoral anti-TFP response, i.e., anti-TFP antibodies having an anti-IgE isotype. It is thought that a patient's antibody producing cells undergo a class switch from IgG isotype (that does not cause anaphylaxis) to IgE isotype when there is a ten to fourteen day break in exposure to antigen. [0760] If a patient is at high risk of generating an anti-TFP antibody response during the course of transient TFP therapy (such as those generated by RNA transductions), the modified immune cell infusion breaks should not last more than ten to fourteen days. Methods of Producing Modified immune, e.g., T cells [0761] Disclosed herein, in some embodiments, are methods of producing the modified T cell of the disclosure, the method comprising (a) disrupting an endogenous TCR gene encoding a TCR alpha chain, a TCR beta chain, a TCR gamma chain, a TCR delta chain, or any combination thereof; thereby producing a T cell containing a functional disruption of an endogenous TCR gene; and (b) transducing the T cell containing a functional disruption of an endogenous TCR gene with the recombinant nucleic acid of the disclosure, or the vectors disclosed herein. In some instances, disrupting comprises transducing the T cell with a nuclease protein or a nucleic acid sequence encoding a nuclease protein that targets the endogenous gene encoding a TCR alpha chain, a TCR beta chain, or a TCR alpha chain and a TCR beta chain. [0762] Further disclosed herein, in some embodiments, are methods of producing the modified T cell of the disclosure, the method comprising transducing a T cell containing a functional disruption of an endogenous TCR gene with the recombinant nucleic acid disclosed herein, or the vectors disclosed herein. In some instances, the T cell containing a functional disruption of an endogenous TCR gene is a T cell containing a functional disruption of an endogenous TCR gene encoding a TCR alpha chain, a TCR beta chain, or a TCR alpha chain and a TCR beta chain. [0763] In some instances, the T cell is a human T cell. In some instances, the T cell containing a functional disruption of an endogenous TCR gene has reduced binding to MHC-peptide complex compared to that of an unmodified control T cell. [0764] In some instances, the nuclease is a meganuclease, a zinc-finger nuclease (ZFN), a transcription activator-like effector nuclease (TALEN), a CRISPR/Cas nuclease, CRISPR/Cas nickase, or a megaTAL nuclease. In some instances, the sequence comprised by the recombinant nucleic acid or the vector is inserted into the endogenous TCR subunit gene at the cleavage site, and wherein the insertion of the sequence into the endogenous TCR subunit gene functionally disrupts the endogenous TCR subunit. In some instances, the nuclease is a meganuclease. In some instances, the meganuclease comprises a first subunit and a second subunit, wherein the first subunit binds to a first recognition half-site of the recognition sequence, and wherein the second subunit binds to a second recognition half-site of the recognition sequence. In some instances, the meganuclease is a single-chain meganuclease comprising a linker, wherein the linker covalently joins the first subunit and the second subunit. Gene Editing Technologies [0765] In some embodiments, the modified immune cells comprising the recombinant nucleic acid comprising a sequence encoding a TFP and an RNAi agent or a sequence encoding the RNAi agent as disclosed herein are further engineered using a gene editing technique such as clustered regularly interspaced short palindromic repeats (CRISPR®, see, e.g., US Patent No. 8,697,359), transcription activator-like effector (TALE) nucleases (TALENs, see, e.g., U.S. Patent No.9,393,257), meganucleases (endodeoxyribonucleases having large recognition sites comprising double-stranded DNA sequences of 12 to 40 base pairs), zinc finger nuclease (ZFN, see, e.g., Urnov et al., Nat. Rev. Genetics (2010) v11, 636-646), or megaTAL nucleases (a fusion protein of a meganuclease to TAL repeats) methods. In this way, a chimeric construct may be engineered to combine desirable characteristics of each subunit, such as conformation or signaling capabilities. See also Sander & Joung, Nat. Biotech. (2014) v32, 347-55; and June et al., 2009 Nature Reviews Immunol.9.10: 704-716, each incorporated herein by reference. In some embodiments, one or more of the extracellular domain, the transmembrane domain, or the cytoplasmic domain of a TFP subunit are engineered to have aspects of more than one natural TCR subunit domain (i.e., are chimeric). [0766] Recent developments of technologies to permanently alter the human genome and to introduce site-specific genome modifications in disease relevant genes lay the foundation for therapeutic applications. These technologies are now commonly known as “genome editing. [0767] The endogenous TCR gene encoding a TCR alpha chain, a TCR beta chain, or a TCR alpha chain and a TCR beta chain can be inactivated in the modified cell (e.g., modified T cell) described herein. The inactivation can include disruption of genomic gene locus, gene silencing, inhibition or reduction of transcription, or inhibition or reduction of translation. The endogenous TCR gene can be silenced, for example, by inhibitory nucleic acids such as siRNA and shRNA. The translation of the endogenous TCR gene can be inhibited by inhibitory nucleic acids such as microRNA. In some embodiments, gene editing techniques are employed to disrupt an endogenous TCR gene. In some embodiments, mentioned endogenous TCR gene encodes a TCR alpha chain, a TCR beta chain, or a TCR alpha chain and a TCR beta chain. In some embodiments, gene editing techniques pave the way for multiplex genomic editing, which allows simultaneous disruption of multiple genomic loci in endogenous TCR gene. In some embodiments, multiplex genomic editing techniques are applied to generate gene-disrupted T cells that are deficient in the expression of endogenous TCR, and/or human leukocyte antigens (HLAs), and/or programmed cell death protein 1 (PD1), and/or other genes. [0768] Current gene editing technologies comprise meganucleases, zinc-finger nucleases (ZFN), TAL effector nucleases (TALEN), and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) system. These four major classes of gene-editing techniques share a common mode of action in binding a user-defined sequence of DNA and mediating a double-stranded DNA break (DSB). DSB may then be repaired by either non-homologous end joining (NHEJ) or –when donor DNA is present- homologous recombination (HR), an event that introduces the homologous sequence from a donor DNA fragment. Additionally, nickase nucleases generate single-stranded DNA breaks (SSB). DSBs may be repaired by single strand DNA incorporation (ssDI) or single strand template repair (ssTR), an event that introduces the homologous sequence from a donor DNA. [0769] Genetic modification of genomic DNA can be performed using site-specific, rare-cutting endonucleases that are engineered to recognize DNA sequences in the locus of interest. Methods for producing engineered, site-specific endonucleases are known in the art. For example, zinc- finger nucleases (ZFNs) can be engineered to recognize and cut predetermined sites in a genome. ZFNs are chimeric proteins comprising a zinc finger DNA-binding domain fused to the nuclease domain of the Fokl restriction enzyme. The zinc finger domain can be redesigned through rational or experimental means to produce a protein that binds to a pre-determined DNA sequence -18 basepairs in length. By fusing this engineered protein domain to the Fokl nuclease, it is possible to target DNA breaks with genome-level specificity. ZFNs have been used extensively to target gene addition, removal, and substitution in a wide range of eukaryotic organisms (reviewed in Durai et al. (2005), Nucleic Acids Res 33, 5978). Likewise, TAL- effector nucleases (TALENs) can be generated to cleave specific sites in genomic DNA. Like a ZFN, a TALEN comprises an engineered, site-specific DNA-binding domain fused to the Fokl nuclease domain (reviewed in Mak et al. (2013), Curr Opin Struct Biol.23:93-9). In this case, however, the DNA binding domain comprises a tandem array of TAL-effector domains, each of which specifically recognizes a single DNA basepair. Compact TALENs have an alternative endonuclease architecture that avoids the need for dimerization (Beurdeley et al. (2013), Nat Commun.4: 1762). A Compact TALEN comprises an engineered, site-specific TAL-effector DNA-binding domain fused to the nuclease domain from the I-TevI homing endonuclease. Unlike Fokl, I-TevI does not need to dimerize to produce a double-strand DNA break so a Compact TALEN is functional as a monomer. [0770] Engineered endonucleases based on the CRISPR/Cas9 system are also known in the art (Ran et al. (2013), Nat Protoc.8:2281-2308; Mali et al. (2013), Nat Methods 10:957-63). The CRISPR gene-editing technology is composed of an endonuclease protein whose DNA-targeting specificity and cutting activity can be programmed by a short guide RNA or a duplex crRNA/TracrRNA. A CRISPR endonuclease comprises two components: (1) a caspase effector nuclease, typically microbial Cas9; and (2) a short “guide RNA” or an RNA duplex comprising a 18 to 20 nucleotide targeting sequence that directs the nuclease to a location of interest in the genome. By expressing multiple guide RNAs in the same cell, each having a different targeting sequence, it is possible to target DNA breaks simultaneously to multiple sites in the genome (multiplex genomic editing). [0771] There are two classes of CRISPR systems known in the art (Adli (2018) Nat. Commun. 9:1911), each containing multiple CRISPR types. Class 1 contains type I and type III CRISPR systems that are commonly found in Archaea. And, Class II contains type II, IV, V, and VI CRISPR systems. Although the most widely used CRISPR/Cas system is the type II CRISPR- Cas9 system, CRISPR/Cas systems have been repurposed by researchers for genome editing. More than 10 different CRISPR/Cas proteins have been remodeled within last few years (Adli (2018) Nat. Commun.9:1911). Among these, such as Cas12a (Cpf1) proteins from Acid- aminococcus sp (AsCpf1) and Lachnospiraceae bacterium (LbCpf1), are particularly interesting. [0772] Homing endonucleases are a group of naturally-occurring nucleases that recognize 15-40 base-pair cleavage sites commonly found in the genomes of plants and fungi. They are frequently associated with parasitic DNA elements, such as group 1 self-splicing introns and inteins. They naturally promote homologous recombination or gene insertion at specific locations in the host genome by producing a double -stranded break in the chromosome, which recruits the cellular DNA-repair machinery (Stoddard (2006), Q. Rev. Biophys.38: 49-95). Specific amino acid substations could reprogram DNA cleavage specificity of homing nucleases (Niyonzima (2017), Protein Eng Des Sel.30(7): 503–522). Meganucleases (MN) are monomeric proteins with innate nuclease activity that are derived from bacterial homing endonucleases and engineered for a unique target site (Gersbach (2016), Molecular Therapy.24: 430–446). In some embodiments, meganuclease is engineered I-CreI homing endonuclease. In other embodiments, meganuclease is engineered I-SceI homing endonuclease. [0773] In addition to mentioned four major gene editing technologies, chimeric proteins comprising fusions of meganucleases, ZFNs, and TALENs have been engineered to generate novel monomeric enzymes that take advantage of the binding affinity of ZFNs and TALENs and the cleavage specificity of meganucleases (Gersbach (2016), Molecular Therapy 24: 430–446). For example, A megaTAL is a single chimeric protein, which is the combination of the easy-to- tailor DNA binding domains from TALENs with the high cleavage efficiency of meganucleases. [0774] In order to perform the gene editing technique, the nucleases, and in the case of the CRISPR/ Cas9 system, a gRNA, may need to be efficiently delivered to the cells of interest. Delivery methods such as physical, chemical, and viral methods are also know in the art (Mali (2013). Indian J. Hum. Genet.19: 3-8.). In some instances, physical delivery methods can be selected from the methods but not limited to electroporation, microinjection, or use of ballistic particles. On the other hand, chemical delivery methods require use of complex molecules such calcium phosphate, lipid, or protein. In some embodiments, viral delivery methods are applied for gene editing techniques using viruses such as but not limited to adenovirus, lentivirus, and retrovirus. [0775] As an example, the endogenous TCR gene (e.g., a TRAC locus or a TRBC locus) encoding a TCR alpha chain, a TCR beta chain, or a TCR alpha chain and a TCR beta chain can be inactivated by CRISPR/Cas9 system. The gRNA used to inactivate (e.g., disrupt) the TRAC locus can comprise a sequence of SEQ ID: 196. The gRNA used to disrupt the TRBC locus can comprise a sequence of SEQ ID: 197. [0776] CTCGACCAGCTTGACATCAC (SEQ ID NO:196). [0777] ACACTGGTGTGCCTGGCCAC (SEQ ID NO:197). Methods of Treatment [0778] Disclosed herein, in some embodiments, are methods of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical compositions disclosed herein. Further disclosed herein, in some embodiments, are methods of treating cancer in a subject in need thereof, the method comprising administering to the subject a pharmaceutical composition comprising (a) a modified T cell produced according to the methods disclosed herein; and (b) a pharmaceutically acceptable carrier. [0779] In some instances, the modified T cell is an allogeneic T cell. In some instances, less cytokines are released in the subject compared a subject administered an effective amount of an unmodified control T cell. In some instances, less cytokines are released in the subject compared a subject administered an effective amount of a modified T cell comprising the recombinant nucleic acid disclosed herein, or the vector disclosed herein. [0780] In some instances, the method comprises administering the pharmaceutical composition in combination with an agent that increases the efficacy of the pharmaceutical composition. In some instances, the method comprises administering the pharmaceutical composition in combination with an agent that ameliorates one or more side effects associated with the pharmaceutical composition. [0781] In some instances, the cancer is a solid cancer, a lymphoma or a leukemia. In some instances, the cancer is selected from the group consisting of renal cell carcinoma, breast cancer, lung cancer, ovarian cancer, prostate cancer, colon cancer, cervical cancer, brain cancer, liver cancer, pancreatic cancer, kidney and stomach cancer. [0782] The present disclosure includes a type of cellular therapy in which modified T cell is infused to a recipient in need thereof, wherein T cells are genetically modified to express a TFP and an RNAi agent as described herein. In some embodiments, modified T cell further expresses a TCR gamma and/or delta constant domain. The infused cell is able to kill tumor cells in the recipient. Unlike antibody therapies, modified T cells are able to replicate in vivo resulting in long-term persistence that can lead to sustained tumor control. In various aspects, the T cells administered to the patient, or their progeny, persist in the patient for at least four months, five months, six months, seven months, eight months, nine months, ten months, eleven months, twelve months, thirteen months, fourteen month, fifteen months, sixteen months, seventeen months, eighteen months, nineteen months, twenty months, twenty-one months, twenty-two months, twenty-three months, two years, three years, four years, or five years after administration of the T cell to the patient. [0783] The present disclosure also includes a type of cellular therapy in which the modified T cell is infused to a recipient in need thereof, wherein T cells are modified, e.g., by in vitro transcribed RNA, to transiently express a TFP and an RNAi agent as described herein. In some embodiments, T cells are further modified to transiently express a TCR gamma and/or delta constant domain. The infused cell is able to kill tumor cells in the recipient. Thus, in various aspects, the T cells administered to the patient, is present for less than one month, e.g., three weeks, two weeks, or one week, after administration of the T cell to the patient. [0784] Without wishing to be bound by any particular theory, the anti-tumor immunity response elicited by the modified T cells may be an active or a passive immune response, or alternatively may be due to a direct vs indirect immune response. [0785] In one aspect, the human modified T cells of the disclosure may be a type of vaccine for ex vivo immunization and/or in vivo therapy in a mammal. In one aspect, the mammal is a human. [0786] With respect to ex vivo immunization, at least one of the following occurs in vitro prior to administering the cell into a mammal: i) expansion of the cells, ii) introducing a nucleic acid encoding a TFP and an RNAi agent or a sequence encoding the RNAi agent to the cells or iii) cryopreservation of the cells. In some embodiments, a nucleic acid encoding a TCR gamma and/or delta constant domain is further introduced to the cells. [0787] Ex vivo procedures are well known in the art and are discussed more fully below. Briefly, cells are isolated from a mammal (e.g., a human) and genetically modified (i.e., transduced or transfected in vitro) with a vector disclosed herein. The modified T cell can be administered to a mammalian recipient to provide a therapeutic benefit. The mammalian recipient may be a human and the modified cell can be autologous with respect to the recipient. Alternatively, the cells can be allogeneic, syngeneic or xenogeneic with respect to the recipient. [0788] The procedure for ex vivo expansion of hematopoietic stem and progenitor cells is described in U.S. Pat. No.5,199,942, incorporated herein by reference, can be applied to the cells of the present disclosure. Other suitable methods are known in the art, therefore the present disclosure is not limited to any particular method of ex vivo expansion of the cells. Briefly, ex vivo culture and expansion of immune, e.g., T, cells comprises: (1) collecting CD34+ hematopoietic stem and progenitor cells from a mammal from peripheral blood harvest or bone marrow explants; and (2) expanding such cells ex vivo. In addition to the cellular growth factors described in U.S. Pat. No.5,199,942, other factors such as flt3-L, IL-1, IL-3 and c-kit ligand, can be used for culturing and expansion of the cells. [0789] In addition to using a cell-based vaccine in terms of ex vivo immunization, the present disclosure also provides compositions and methods for in vivo immunization to elicit an immune response directed against an antigen in a patient. [0790] Generally, the cells activated and expanded as described herein may be utilized in the treatment and prevention of diseases that arise in individuals who are immunocompromised. [0791] The modified T cells of the present disclosure may be administered either alone, or as a pharmaceutical composition in combination with diluents and/or with other components such as IL-2 or other cytokines or cell populations. Combination Therapies [0792] A modified immune cells, e.g., T cell described herein may be used in combination with other known agents and therapies. Administered “in combination”, as used herein, means that two (or more) different treatments are delivered to the subject during the course of the subject’s affliction with the disorder, e.g., the two or more treatments are delivered after the subject has been diagnosed with the disorder and before the disorder has been cured or eliminated or treatment has ceased for other reasons. In some embodiments, the delivery of one treatment is still occurring when the delivery of the second begins, so that there is overlap in terms of administration. This is sometimes referred to herein as “simultaneous” or “concurrent delivery”. In other embodiments, the delivery of one treatment ends before the delivery of the other treatment begins. In some embodiments of either case, the treatment is more effective because of combined administration. For example, the second treatment is more effective, e.g., an equivalent effect is seen with less of the second treatment, or the second treatment reduces symptoms to a greater extent, than would be seen if the second treatment were administered in the absence of the first treatment or the analogous situation is seen with the first treatment. In some embodiments, delivery is such that the reduction in a symptom, or other parameter related to the disorder is greater than what would be observed with one treatment delivered in the absence of the other. The effect of the two treatments can be partially additive, wholly additive, or greater than additive. The delivery can be such that an effect of the first treatment delivered is still detectable when the second is delivered. [0793] In some embodiments, the “at least one additional therapeutic agent” includes a modified immune cells, e.g., T cell. Also provided are T cells that express multiple TFPs, which bind to the same or different target antigens, or same or different epitopes on the same target antigen, multiple RNAi agents as described herein, which targets the same or different targets, or a combination thereof. Also provided are populations of T cells in which a first subset of T cells express a first TFP and a first RNAi agent as described herein, and a second subset of T cells express a second TFP and a second RNAi agent as described herein. [0794] A modified immune cells, e.g., T cell described herein and the at least one additional therapeutic agent can be administered simultaneously, in the same or in separate compositions, or sequentially. For sequential administration, the modified T cell described herein can be administered first, and the additional agent can be administered second, or the order of administration can be reversed. [0795] In further aspects, a modified immune cells, e.g., T cell described herein may be used in a treatment regimen in combination with surgery, chemotherapy, radiation, immunosuppressive agents, such as cyclosporin, azathioprine, methotrexate, mycophenolate, and tacrolimus, antibodies, or other immunoablative agents such as alemtuzumab, anti-CD3 antibodies or other antibody therapies, cytoxin, fludarabine, cyclosporin, tacrolimus, rapamycin, mycophenolic acid, steroids, romidepsin, cytokines, and irradiation. peptide vaccine, such as that described in Izumoto et al., 2008 J. Neurosurg.108:963-971. [0796] In one embodiment, the subject can be administered an agent which reduces or ameliorates a side effect associated with the administration of a modified immune cell, e.g., T cell. Side effects associated with the administration of a modified immune cell, e.g., T cell include but are not limited to cytokine release syndrome (CRS), and hemophagocytic lymphohistiocytosis (HLH), also termed Macrophage Activation Syndrome (MAS). Symptoms of CRS include high fevers, nausea, transient hypotension, hypoxia, and the like. Accordingly, the methods disclosed herein can comprise administering a modified T cell described herein to a subject and further administering an agent to manage elevated levels of a soluble factor resulting from treatment with a modified T cell. In one embodiment, the soluble factor elevated in the subject is one or more of IFN-γ, TNFα, IL-2 and IL-6. Therefore, an agent administered to treat this side effect can be an agent that neutralizes one or more of these soluble factors. Such agents include, but are not limited to a steroid, an inhibitor of TNFα, and an inhibitor of IL-6. An example of a TNFα inhibitor is entanercept. An example of an IL-6 inhibitor is tocilizumab (toc). [0797] In one embodiment, the subject can be administered an agent which enhances the activity of a modified immune cell, e.g., T cell. For example, in one embodiment, the agent can be an agent which inhibits an inhibitory molecule. Inhibitory molecules, e.g., Programmed Death 1 (PD1), can, in some embodiments, decrease the ability of a modified T cell to mount an immune effector response. Examples of inhibitory molecules include PD1, PD-L1, CTLA4, TIM3, LAG3, VISTA, BTLA, TIGIT, LAIR1, CD160, 2B4 and TGFR beta. Inhibition of an inhibitory molecule, e.g., by inhibition at the DNA, RNA or protein level, can optimize a modified T cell performance. In embodiments, an inhibitory nucleic acid, e.g., an inhibitory nucleic acid, e.g., a dsRNA, e.g., an siRNA or shRNA, can be used to inhibit expression of an inhibitory molecule in the cell expressing a TFP and an RNAi agent as described herein. In an embodiment the inhibitor is a shRNA. In an embodiment, the inhibitory molecule is inhibited within a modified T cell. In these embodiments, a dsRNA molecule that inhibits expression of the inhibitory molecule is linked to the nucleic acid that encodes a component, e.g., all of the components, of the TFP. In one embodiment, the inhibitor of an inhibitory signal can be, e.g., an antibody or antibody fragment that binds to an inhibitory molecule. For example, the agent can be an antibody or antibody fragment that binds to PD1, PD-L1, PD-L2 or CTLA4 (e.g., ipilimumab (also referred to as MDX-010 and MDX-101, and marketed as Yervoy®; Bristol-Myers Squibb; tremelimumab (IgG2 monoclonal antibody available from Pfizer, formerly known as ticilimumab, CP- 675,206)). In an embodiment, the agent is an antibody or antibody fragment that binds to TIM3. In an embodiment, the agent is an antibody or antibody fragment that binds to LAG3. [0798] In some embodiments, the agent which enhances the activity of a modified T cell can be, e.g., a fusion protein comprising a first domain and a second domain, wherein the first domain is an inhibitory molecule, or fragment thereof, and the second domain is a polypeptide that is associated with a positive signal, e.g., a polypeptide comprising an intracellular signaling domain as described herein. In some embodiments, the polypeptide that is associated with a positive signal can include a costimulatory domain of CD28, CD27, ICOS, e.g., an intracellular signaling domain of CD28, CD27 and/or ICOS, and/or a primary signaling domain, e.g., of CD3 zeta, e.g., described herein. In one embodiment, the fusion protein is expressed by the same cell that expressed the TFP. In another embodiment, the fusion protein is expressed by a cell, e.g., a T cell that does not express an anti-TAA TFP. EXAMPLES [0799] The invention is further described in detail by reference to the following experimental examples. These examples are provided for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Thus, the invention should in no way be construed as being limited to the following examples, but rather, should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. Without further description, it is believed that one of ordinary skill in the art can, using the preceding description and the following illustrative examples, make and utilize the compounds of the present invention and practice the claimed methods. The following working examples specifically point out various aspects of the present invention, and are not to be construed as limiting in any way the remainder of the disclosure. Background for Examples [0800] T-Cell Receptor (TCR) is formed by a complex of dimers TCRα/β, CD3γ/ε, CD3δ/ε and the homodimer CD3ζ/ζ. In some particular T cells, TCR γ/δ are expressed instead of TCRα/β to form a functional TCR. TCRα/β/γ/δ have a constant domain common to all T-cells and a variable domain specific to an antigen. TRAC, TRBC, TRGC and TRDC genes encode for the constant C-terminal region of TCRα, TCRβ, TCRγ and TCRδ respectively. Despite high structural homology between those molecules, TCRα only pairs with TCRβ and TCRγ only pairs with TCRδ. Hence, a TCR complex is formed with TCRα/β in α/β T cells or with TCRγ/δ in γ/δ T cells. Example 1. shRNA and mirtron design [0801] shRNA targeting B2M was designed under control of the U6 promoter. Exemplary guide and passenger strands targeting B2M are SEQ ID NO:167 and SEQ ID NO:166 respectively. In some instances, the shRNA is expressed from a vector further expressing one or more polypeptides. In some instances, the polypeptide is a truncated EGFR protein. In some instances, the polypeptide is one or more TFP constructs and/or TRAC and TRBC constant domains described herein. In some instances, the shRNA is positioned upstream of the promoter expressing the additional polypeptides, as is illustrated in FIG.1. [0802] A mirtron system was designed with B2M shRNA targeting sequence within a synthetic miRNA scaffold (identified herein as a pri-shRNAmiR or mirtron). The scaffold is a modified version of murine miR-155 described in Fowler et al. (NAR 2015). The mirtron system comprises a 5’ scaffold of SEQ ID NO:160 and SEQ ID NO:161, a guide strand, a pri-miR loop domain of SEQ ID NO:162, a passenger strand, and a 3’ scaffold of SEQ ID NO:163 and SEQ ID NO:164. A version based off of human miR-155 was also tested. Exemplary guide and passenger strands targeting B2M are SEQ ID NO:187 and SEQ ID NO:185 respectively. In some instances, the mirtron is expressed from a vector further expressing one or more polypeptides. In some instances, the polypeptide is a truncated EGFR protein. In some instances, the polypeptide is one or more TFP constructs and/or TRAC and TRBC constant domains described herein. In some instances, the additional polypeptides are expressed under the control of the EF1α promoter, and the mirtron is contained within an intron of the EF1α promoter. In such instances, the EF1α promoter also drives expression of the mirtron. This is illustrated in FIG.1. Example 2: Efficacy of B2M Knockdown with truncated EGFR constructs [0803] Lentivirus encoding truncated EGFR transgenes were introduced into T cells using lentiviruses as described, e.g., in copending PCT Patent Application No. PCT/US2020/050503, the entirety of which is incorporated by reference herein. Phenotypic characterization of T cells [0804] T cells were (i) untransduced as a negative control; (ii) transduced with a transgene encoding truncated EGFR under the control of the EF1a promoter and having a negative control shRNA upstream of the EF1a promoter; (iii) transduced with a transgene encoding truncated EGFR under the control of the EF1a promoter and having a B2M shRNA under the control of the U6 promoter upstream of the EF1a promoter; (iv) transduced with a transgene encoding truncated EGFR under the control of the EF1a promoter and having a murine B2M mirtron in the intron of the EF1a promoter; and (v) transduced with a transgene encoding truncated EGFR under the control of the EF1a promoter and having a human B2M mirtron in the intron of the EF1a promoter. Transduction efficacy, B2M knockdown, and MHC1 knockdown were assessed by flow cytometry. [0805] Staining for EGFR shows that a transduction efficiency of at least 35% was achieved in all transduced cells (FIG.2). FIG.2A shows B2M and MHC1 levels in EGFR+ cells. B2M levels were substantially decreased in cells transduced with the B2M shRNA or with the murine B2M mirtron (based on the murine mir-155 scaffold). A relative decrease in MHC1 levels was also observed. No significant reduction was seen with the control shRNA or with the mirtron based on the human mir-155 scaffold. FIG.2B shows B2M and MHC1 levels in EGFR- cells from the same population. No decrease in B2M levels was seen in cells transduced with the B2M shRNA, and only a modest decrease in B2M levels was seen in cells transduced with the B2M murine mirtron. This suggests that both the B2M shRNA and the B2M mirtron based on the murine mir-155 scaffold can effectively reduce B2M levels, thereby reducing MHC1 levels. No further experiments were done with the mirtron based on the human mir-155 scaffold. Example 3: Generation of T cell receptor fusion proteins Source of TCR Subunits [0806] A TCR complex contains the CD3-epsilon polypeptide, the CD3-gamma poly peptide, the CD3-delta polypeptide, and the TCR alpha chain polypeptide and the TCR beta chain polypeptide or the TCR delta chain polypeptide and the TCR gamma chain polypeptide. TCR alpha, TCR beta, TCR gamma, and TCR delta recruit the CD3 zeta polypeptide. The TFPs described in the examples comprise a binder linked to at least a portion of one of the TCR subunits described above. The terms “TFP” and “TRuC” are used interchangeably in these examples. The human CD3-epsilon polypeptide canonical sequence is Uniprot Accession No. P07766. The human CD3-gamma polypeptide canonical sequence is Uniprot Accession No. P09693. The human CD3-delta polypeptide canonical sequence is Uniprot Accession No. P043234. The human CD3-zeta polypeptide canonical sequence is Uniprot Accession No. P20963. The human TCR alpha chain canonical sequence is Uniprot Accession No. Q6ISU1. The murine TCR alpha chain canonical sequence is Uniprot Accession No. A0A075B662. The human TCR beta chain constant region canonical sequence is Uniprot Accession No. P01850. The murine TCR beta chain constant region canonical sequence is Uniprot Accession No. P01852. [0807] The human CD3-epsilon polypeptide canonical sequence is: MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILW QHNDKNIGGDEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARV CENCMEMDVMSVATIVIVDICITGGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQ NKERPPPVPNPDYEPIRKGQRDLYSGLNQRRI (SEQ ID NO:124). [0808] The mature human CD3-epsilon polypeptide sequence is: DGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDEDHL SLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMDVMSVATIVIVDICIT GGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQNKERPPPVPNPDYEPIRKGQRDL YSGLNQRRI (SEQ ID NO:258). [0809] The signal peptide of human CD3ε is: MQSGTHWRVLGLCLLSVGVWGQ (SEQ ID NO:125). [0810] The extracellular domain of human CD3ε is: DGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDEDHL SLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMD (SEQ ID NO:126). [0811] The transmembrane domain of human CD3ε is: VMSVATIVIVDICITGGLLLLVYYWS (SEQ ID NO:127). [0812] The intracellular domain of human CD3ε is: KNRKAKAKPVTRGAGAGGRQRGQNKERPPPVPNPDYEPIRKGQRDLYSGLNQRRI (SEQ ID NO:128). [0813] The human CD3-gamma polypeptide canonical sequence is: MEQGKGLAVLILAIILLQGTLAQSIKGNHLVKVYDYQEDGSVLLTCDAEAKNITWFKDG KMIGFLTEDKKKWNLGSNAKDPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATIS GFLFAEIVSIFVLAVGVYFIAGQDGVRQSRASDKQTLLPNDQLYQPLKDREDDQYSHLQ GNQLRRN (SEQ ID NO:129). [0814] The mature human CD3-gamma polypeptide sequence is: QSIKGNHLVKVYDYQEDGSVLLTCDAEAKNITWFKDGKMIGFLTEDKKKWNLGSNAK DPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATISGFLFAEIVSIFVLAVGVYFIAG QDGVRQSRASDKQTLLPNDQLYQPLKDREDDQYSHLQGNQLRRN (SEQ ID NO:130). [0815] The signal peptide of human CD3γ is: MEQGKGLAVLILAIILLQGTLA (SEQ ID NO:131). [0816] The extracellular domain of human CD3γ is: QSIKGNHLVKVYDYQEDGSVLLTCDAEAKNITWFKDGKMIGFLTEDKKKWNLGSNAK DPRGMYQCKGSQNKSKPLQVYYRMCQNCIELNAATIS (SEQ ID NO:132). [0817] The transmembrane domain of human CD3 γ is: GFLFAEIVSIFVLAVGVYFIA (SEQ ID NO:133). [0818] The intracellular domain of human CD3γ is: GQDGVRQSRASDKQTLLPNDQLYQPLKDREDDQYSHLQGNQLRRN (SEQ ID NO:134). [0819] The human CD3-delta polypeptide canonical sequence is: MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLG KRILDPRGIYRCNGTDIYKDKESTVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLALG VFCFAGHETGRLSGAADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNKS (SEQ ID NO:135). [0820] The mature human CD3-delta polypeptide sequence is: FKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDKE STVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLALGVFCFAGHETGRLSGAADTQAL LRNDQVYQPLRDRDDAQYSHLGGNWARNKS (SEQ ID NO:136). [0821] The signal peptide of human CD3δ is: MEHSTFLSGLVLATLLSQVSP (SEQ ID NO:137). [0822] The extracellular domain of human CD3δ is: FKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDKE STVQVHYRMCQSCVELDPATVA (SEQ ID NO:138). [0823] The transmembrane domain of human CD3δ is: GIIVTDVIATLLLALGVFCFA (SEQ ID NO:139). [0824] The intracellular domain of human CD3δ is: GHETGRLSGAADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNK (SEQ ID NO:140). [0825] The human CD3-zeta polypeptide canonical sequence is: MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFIYGVILTALFLRVKFSRSADA PAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDK MAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR (SEQ ID NO:141). [0826] The human TCR alpha chain constant region canonical sequence is: IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSN SAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLSVIGFR ILLLKVAGFNLLMTLRLWSS (SEQ ID NO:142). [0827] The human TCR alpha chain human IgC sequence is: IQNPDPAVYQLRDSKSSDKSVCLFTDFDSQTNVSQSKDSDVYITDKTVLDMRSMDFKSN SAVAWSNKSDFACANAFNNSIIPEDTFFPSPESSCDVKLVEKSFETDTNLNFQNLS (SEQ ID NO:143) [0828] The transmembrane domain of the human TCR alpha chain is: VIGFRILLLKVAGFNLLMTLRLW (SEQ ID NO:144). [0829] The intracellular domain of the human TCR alpha chain is: SS (SEQ ID NO:145) [0830] The murine TCR alpha chain constant (mTRAC) region canonical sequence is: XIQNPEPAVYQLKDPRSQDSTLCLFTDFDSQINVPKTMESGTFITDKTVLDMKAMDSKS NGAIAWSNQTSFTCQDIFKETNATYPSSDVPCDATLTEKSFETDMNLNFQNLSVMGLRIL LLKVAGFNLLMTLRLWSS (SEQ ID NO:146). [0831] The transmembrane domain of the murine TCR alpha chain is: MGLRILLLKVAGFNLLMTLRLW (SEQ ID NO:147). [0832] The intracellular domain of the murine TCR alpha chain is: SS [0833] The human TCR beta 1 chain constant region (mTRBC) canonical sequence is: EDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTD PQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPV TQIVSAEAWGRADCGFTSVSYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRK DF (SEQ ID NO:148). [0834] The human TCR beta 1 chain human IgC sequence is: EDLNKVFPPEVAVFEPSEAEISHTQKATLVCLATGFFPDHVELSWWVNGKEVHSGVSTD PQPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPV TQIVSAEAWGRADCGFTSVSYQQGVLSATILYE (SEQ ID NO:149) [0835] The transmembrane domain of the human TCR beta 1 chain is: ILLGKATLYAVLVSALVLMAM (SEQ ID NO:150). [0836] The intracellular domain of the human TCR beta 1 chain is: VKRKDF (SEQ ID NO:151) [0837] The murine TCR beta 1 chain constant region canonical sequence is: EDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVST DPQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNI SAEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS (SEQ ID NO:152). [0838] The transmembrane domain of the murine TCR beta 1 chain is: ILYEILLGKATLYAVLVS TLVVMAMVK (SEQ ID NO:153). [0839] The intracellular domain of the murine TCR beta 1 chain is: KRKNS (SEQ ID NO:154) [0840] The human TCR beta 2 chain C region canonical sequence is: DLKNVFPPKVAVFEPSEAEISHTQKATLVCLATGFYPDHVELSWWVNGKEVHSGVSTDP QPLKEQPALNDSRYCLSSRLRVSATFWQNPRNHFRCQVQFYGLSENDEWTQDRAKPVT QIVSAEAWGRADCGFTSESYQQGVLSATILYEILLGKATLYAVLVSALVLMAMVKRKDS RG (SEQ ID NO:371) [0841] The transmembrane domain of the human TCR beta 2 chain is: TILYEILLGKATLYAVLVSALVL (SEQ ID NO:372) [0842] The intracellular domain of the human TCR beta 2 chain is: MAMVKRKDSRG (SEQ ID NO:373) [0843] The murine TCR beta 2 chain C region canonical sequence is: EDLRNVTPPKVSLFEPSKAEIANKQKATLVCLARGFFPDHVELSWWVNGKEVHSGVSTD PQAYKESNYSYCLSSRLRVSATFWHNPRNHFRCQVQFHGLSEEDKWPEGSPKPVTQNIS AEAWGRADCGITSASYQQGVLSATILYEILLGKATLYAVLVSTLVVMAMVKRKNS (SEQ ID NO:152) [0844] The transmembrane domain of the murine TCR beta 2 chain is: ILYEILLGKATLYAVLVS TLVVMAMVK (SEQ ID NO:153) [0845] The intracellular domain of the murine TCR beta 2 chain is: KRKNS (SEQ ID NO:154) [0846] The human TCR gamma chain constant region canonical sequence is: DKQLDADVSPKPTIFLPSIAETKLQKAGTYLCLLEKFFPDVIKIHWQEKKSNTILGSQEGN TMKTNDTYMKFSWLTVPEKSLDKEHRCIVRHENNKNGVDQEIIFPPIKTDVITMDPKDN CSKDANDTLLLQLTNTSAYYMYLLLLLKSVVYFAIITCCLLRRTAFCCNGEKS (SEQ ID NO:21). [0847] The human TCR gamma human IgC sequence is: DKQLDADVSPKPTIFLPSIAETKLQKAGTYLCLLEKFFPDVIKIHWQEKKSNTILGSQEGN TMKTNDTYMKFSWLTVPEKSLDKEHRCIVRHENNKNGVDQEIIFPPIKTDVITMDPKDN CSKDANDTLLLQLTNTSA (SEQ ID NO:155) [0848] The transmembrane domain of the human TCR gamma chain is: YYMYLLLLLKSVVYFAIITCCLL (SEQ ID NO:156). [0849] The intracellular domain of the human TCR gamma chain is: RRTAFCCNGEKS (SEQ ID NO:157) [0850] The human TCR delta chain C region canonical sequence is: SQPHTKPSVFVMKNGTNVACLVKEFYPKDIRINLVSSKKITEFDPAIVISPSGKYNAVKLG KYEDSNSVTCSVQHDNKTVHSTDFEVKTDSTDHVKPKETENTKQPSKSCHKPKAIVHTE KVNMMSLTVLGLRMLFAKTVAVNFLLTAKLFFL (SEQ ID NO:243). [0851] The human TCR delta human IgC sequence is: SQPHTKPSVFVMKNGTNVACLVKEFYPKDIRINLVSSKKITEFDPAIVISPSGKYNAVKLG KYEDSNSVTCSVQHDNKTVHSTDFEVKTDSTDHVKPKETENTKQPSKSCHKPKAIVHTE KVNMMSLTV (SEQ ID NO:265) [0852] The transmembrane domain of the human TCR delta chain is: LGLRMLFAKTVAVNFLLTAKLFF (SEQ ID NO:158). [0853] The intracellular domain of the human TCR delta chain is: L Expression of murine TCRβ/α TFP [0854] TCRα negative cells still express TCRβ and, reciprocally, TCRα is expressed in TCRβ negative cells; However, TCRα or TCRβ TFPs generated by assembling the constant domains of TCRα and/or TCRβ with an antigen binder (e.g., scFv or sdAb) can pair with the constant domain of TCRα or TCRβ. However, the constant domain of human TCRα and TCβ is not able to migrate to the cell surface. Murine or human murine chimera TCRα and TCRβ constant domains can be used. Murine anti-CD19 TCRα TFP including the murine TCRα constant, intracellular, and transmembrane domains and a protein comprising the TCRβ constant, intracellular, and transmembrane domains were expressed together in TRA-/- cells or in TRB-/- cells. In one embodiment, TCRα TFPs were generated by assembling the constant domain of TCRα with an antigen binder (e.g., scFv or sdAb). Example 4: Efficacy of B2M Knockdown in TFP T cells [0855] Lentivirus encoding the MH1e transgene (anti-mesothelin VHH fused to CD3e, TC-210) with and without the murine B2M mirtron were transduced into HLA-A2 expressing T cells as described, e.g., in copending PCT Patent Application No. PCT/US2020/050503. Transduction efficacy, B2M knockdown, and HLA-A2 knockdown were assessed by flow cytometry. [0856] Staining for TFP expression shows that transduction efficiency of at least 36.5% was achieved with the MH1e TFP containing the B2M mirtron. Transduction efficiency is shown in FIG. 3A. FIG. 3B shows B2M and HLA-A2 levels in TFP+ cells. B2M levels were substantially decreased in cells transduced with the B2M mirtron. A relative decrease in HLA- A2 levels was also observed. FIG.3C shows B2M and HLA-A2 levels in TFP- cells from the same population. Only a modest decrease in B2M levels was seen in cells transduced with the B2M mirtron. This suggests that the B2M mirtron can effectively reduce B2M levels, thereby reducing HLA-A2 levels. Example 5: Efficacy of B2M knockdown in allogeneic T cell receptor fusion protein T cells B2M knockdown in Jurkat cells transduced with TFPs [0857] TRA-/- or non-edited Jurkat cells were generated as described previously in in co-pending PCT Patent Application No. PCT/US2020/050503. Following activation, cells were transduced with lentiviruses having transgenes encoding the TFPs described according to the methods described, e.g., in co-pending PCT Patent Application No. PCT/US2020/050503. Cells were expanded for 7 days post activation, and transduction efficacy and B2M expression was then assessed by flow cytometry. A schematic illustrating the process for generating the cells and the TFPs transduced is shown in FIG.4. [0858] The Jurkat cells generated included (i) nontransduced control cells, (ii) non-edited cells expressing anti-CD19 (FMC63) fused to CD3ε (TC-110); (ii) TRA-/- cells expressing FMC63- murine-alpha constant domain fusion and FMC63-murine-beta constant domain fusion (mm FMC63-αC FMC63-βC), and (iv) mm FMC63-αC FMC63-βC with the B2M mirtron. [0859] Staining for TFP expression shows that high transduction efficiency was achieved with TC-110 and with mm FMC63-αC FMC63-βC with or without the B2M mirtron (FIG.5). FIG.5 shows B2M levels were decreased in transduced FMC63-αC FMC63-βC cells having the B2M mirtron relative to FMC63-αC FMC63-βC cells without the B2M mirtron or TC-110 cells. This suggests that the B2M mirtron can effectively reduce B2M levels in allogeneic TFP cells. B2M knockdown in donor-derived T cells transduced with TFPs [0860] TFP transgenes were transduced into T cells using lentiviruses as described, e.g., in copending PCT Patent Application No. PCT/US2020/050503. T cells were activated and transduced one day following activation. At day four following activation, transduced T cells were edited to knock out TRAC as described, e.g., in copending PCT Patent Application No. PCT/US2020/050503. Transduction efficacy and B2M expression was assessed by flow cytometry at 7 days post-activation. A schematic illustrating the process for generating the cells is shown in FIG.6. Phenotypic characterization of Allogeneic-TFP T cells [0861] Allogenic-TFP T cells were examined for their expression of the transduced TFP, as well as expression of B2M and HLA-A2. The following cell types with the transgenes shown were evaluated:
Figure imgf000219_0001
[0862] Results are shown in FIGs 7 and 8. FIG.7 shows that post TFP transduction and TRAC editing, TRA-/- T cells expressing the MH1e-αC P2A MH1e-βC transgene with the B2M mirtron exhibit a decrease in B2M levels relative to edited MH1e-αC P2A MH1e-βC without the mirtron and relative to unedited TC-210 cells. [0863] FIG.8A shows transduction efficiency of transgenes with and without the B2M mirtron into T cells. FIG.8B shows that expression shows that the expression of the B2M mirtron in edited MH1e-αC P2A MH1e-βC TFP+ T cells results in a reduction in B2M expression relative to edited MH1e-αC P2A MH1e-βC TFP+ T cells lacking the B2M mirtron. FIG.8C shows that the same level of reduction in B2M expression is not seen in TFP- cells lacking the transgene. FIGs 8D and 8E show that, in the cells with reduced B2M levels due to the introduction of the B2M mirtron, a reduction of HLA-A2 levels is also seen, and this is not observed in TFP- cells lacking the transgene. These results demonstrate that the B2M mirtron effectively reduce B2M levels in TFP+ allogeneic T cells. Cytotoxicity of allogeneic TCR T cells expressing TFPs [0864] The luciferase-based cytotoxicity assay (“Luc-Cyto” assay) assesses the cytotoxicity of TFP T cells by indirectly measuring the luciferase enzymatic activity in the residual live target cells after co-culture. The target cells used in the Luc-Cyto assay were MSTO-msln-Luc (MSLN positive) and C30-Luc (MSLN negative), each of which stably express firefly luciferase. [0865] The Luc-Cyto assay was set up by mixing T cells (nontransduced, non-edited transduced with MH1-CD3e, or TRA-/- MH1e-αC P2A MH1e-βC with or without the B2M mirtron) with target tumor cells at different effector (T cell) to target (tumor cell) (E-to-T) ratios. The target cells (MSTO-msln-Luc or C30-Luc) were plated at 10,000 cells per well in 96-well plates with RPMI-1640 medium supplemented with 10% heat-inactivated (HI) FBS. Allogeneic TFP T cells were added to the tumor cells at E-to-T ratios of 9:1, 3:1, or 1:1. The mixtures of cells were incubated for 24 hours at 37oC with 5 % CO2. Luciferase enzymatic activity was measured using the Bright-Glo™ Luciferase Assay System (Promega), which measures activity from the residual live target cells in the T cell and tumor cell co-culture. [0866] Results are shown in FIG.9. The allogeneic TRA-/- MH1e-αC P2A MH1e-βC T cells with or without the B2M mirtron showed robust and specific lysis against MSLN positive tumor cells MSTO-msln-Luc that was comparable to TC-210 (MH1-CD3e), but not the MLSN negative tumor cells C30-Luc, indicating that the B2M mirtron does not interfere with cytotoxicity of the allogeneic T cells. Example 6: B2M knock-down construct design [0867] To test B2M knock-down as a method of making allogeneic T cell receptor fusion protein (TFP or TRuC) T cells a series of constructs were designed, incorporated into lentiviral vectors, transduced into T cells, and tested (e.g., SEQ ID NO:2-15, or 65-68). These constructs are outlined in Tables 2, 3, 4, and 5. Several RNAi agents were tested, including a pri-miRNA (“eSIBR”; SEQ ID NO:168) having a guide strand sequence of TAGTACAAGAGATAGAGAGACC (SEQ ID NO:284), a loop sequence of TTTTGGCCTCTGACTGA (SEQ ID NO:285), and a passenger strand sequence of GGTCTCCTACTCTTGTACTACA (SEQ ID NO:286), which was incorporated into the EF1a promoter/intron region of the construct, upstream of the sequence encoding the transgene (e.g., TFP or trEGFR). A variant of this pri-miRNA (“hsa-eSIBR”) was also prepared and tested and included guide strand TAGTACAAGACATACAAAGACC (SEQ ID NO:379) and passenger strand GGTCTTTTATTCTTGTACTACA (SEQ ID NO:381). A negative pri-miRNA control construct comprising guide sequence TCGGTAGGTACATAGAGCGACC (SEQ ID NO:296) and passenger sequence GGTCGCCTAGTACCTACCGACA (SEQ ID NO:297) was also used. As an alternative strategy, an shRNA driven by the human U6 promoter was also tested, having guide strand TAGTACAAGAGATAGAAA (SEQ ID NO:187), loop CCTGACCCA (SEQ ID NO:186) and passenger strand TTTCTATCTCTTGTACTA (SEQ ID NO:185). The human U6 promoter and shRNA elements were placed upstream of the EF1a intron and sequence regions encoding the transgene (e.g., TFP or trEGFR). Negative shRNA control constructs included guide strand TCGGTACGATCGCGGCGG (SEQ ID NO:343) and passenger strand CCGCCGCGATCGTACCGA (SEQ ID NO:342). [0868] These studies showed both successful knockdown of B2M and expression of the transgene (e.g., TFP or trEGFR). Example 7: Additional B2M knock-down construct design [0869] Though the constructs described in Example 6 showed efficient knock-down of B2M, the transgene expression was reduced when compared to transgene expression seen with constructs that did not include the RNAi agent. To test whether altering the location of the RNAi agent within the construct could improve expression, a new set of constructs was designed (e.g., SEQ ID NO:71, 159, 192-194, 198, 199, or 221-224). These constructs and components thereof are outlined in Tables 2, 3, 4, and 5. Each included the pri-miRNA (“eSIBR”; SEQ ID NO:168) having guide strand sequence TAGTACAAGAGATAGAGAGACC (SEQ ID NO:284), loop sequence TTTTGGCCTCTGACTGA (SEQ ID NO:285), and passenger strand sequence GGTCTCCTACTCTTGTACTACA (SEQ ID NO:286), however the localization of these sequences was altered (e.g., moved toward the 5’ or 3’ end of the EF1a intron). In most cases, the pri-miRNA, incorporated into the EF1a intron, was retained in an upstream position relative to the sequences encoding the transgene (e.g., SEQ ID NO:71, 159, 192-194, 198, 199, or 221). In some cases, the pri-miRNA sequences were inserted downstream of the sequence encoding the transgene (e.g., SEQ ID NO:222, 223, or 224), with or without being incorporated into an EF1a intron. In addition to the pri-miRNA, each of these constructs also included sequences encoding a TFP or TRuC (e.g., the transgene). The first TFP (“TC-210”; SEQ ID NO:195) included sequence regions encoding a signal peptide (SEQ ID NO:201), a mesothelin (MSLN) binding sdAb (SEQ ID NO:69), a linker (SEQ ID NO:214) and a CD3 epsilon (SEQ ID NO:258). The second TFP (SEQ ID NO:226) included sequence regions encoding a signal peptide (SEQ ID NO:201), a mesothelin (MSLN) binding sdAb (SEQ ID NO:69), a TCR delta constant domain (SEQ ID NO:243, a furin cleavage site (RRKR (SEQ ID NO:229)), a linker (SEQ ID NO:208), a second signal peptide (SEQ ID NO:201), a second mesothelin (MSLN) binding sdAb (SEQ ID NO:69), and a TCR gamma constant domain (SEQ ID NO:21). Table 1. Exemplary Antigen Binding Domain Sequences.
Figure imgf000222_0001
Figure imgf000223_0001
Figure imgf000224_0001
Figure imgf000225_0001
Figure imgf000226_0001
Figure imgf000227_0001
Table 2. Components of Exemplary Constructs – Amino Acid Sequences
Figure imgf000227_0002
Figure imgf000228_0001
Figure imgf000229_0001
Figure imgf000230_0001
Figure imgf000231_0001
Table 3. Components of Exemplary Constructs – Nucleic Acic Sequences
Figure imgf000231_0002
Figure imgf000232_0001
Figure imgf000233_0001
Figure imgf000234_0001
Figure imgf000235_0001
Figure imgf000236_0001
Figure imgf000237_0001
Figure imgf000238_0002
Table 4. Exemplary Constructs Amino Acid Sequences.
Figure imgf000238_0001
Figure imgf000239_0001
Figure imgf000240_0001
Figure imgf000241_0001
Figure imgf000242_0001
Figure imgf000243_0001
Figure imgf000244_0001
Figure imgf000245_0001
Figure imgf000246_0001
Figure imgf000247_0001
Figure imgf000248_0001
Figure imgf000249_0002
Table 5. Exemplary Constructs Nucleic Acid Sequences.
Figure imgf000249_0001
Figure imgf000250_0001
Figure imgf000251_0001
Figure imgf000252_0001
Figure imgf000253_0001
Figure imgf000254_0001
Figure imgf000255_0001
Figure imgf000256_0001
Figure imgf000257_0001
Figure imgf000258_0001
Figure imgf000259_0001
Figure imgf000260_0001
Figure imgf000261_0001
Figure imgf000262_0001
Figure imgf000263_0001
Figure imgf000264_0001
Figure imgf000265_0001
Figure imgf000266_0001
Figure imgf000267_0001
Figure imgf000268_0001
Figure imgf000269_0001
Figure imgf000270_0001
Figure imgf000271_0001
Figure imgf000272_0001
Figure imgf000273_0001
Figure imgf000274_0001
Figure imgf000275_0001
Figure imgf000276_0001
Figure imgf000277_0001
Figure imgf000278_0001
Figure imgf000279_0001
Figure imgf000280_0001
Figure imgf000281_0001
Figure imgf000282_0001
Figure imgf000283_0001
Figure imgf000284_0001
Figure imgf000285_0001
Figure imgf000286_0001
Figure imgf000287_0001
Figure imgf000288_0001
Figure imgf000289_0001
Figure imgf000290_0001
Figure imgf000291_0001
Figure imgf000292_0001
Figure imgf000293_0001
Figure imgf000294_0001
Figure imgf000295_0001
Figure imgf000296_0001
Figure imgf000297_0001
Figure imgf000298_0001
Figure imgf000299_0001
Figure imgf000300_0001
Figure imgf000301_0001
Figure imgf000302_0001
Figure imgf000303_0001
Figure imgf000304_0001
Figure imgf000305_0001
Figure imgf000306_0001
Figure imgf000307_0001
Figure imgf000308_0001
Figure imgf000309_0001
Figure imgf000310_0001
Figure imgf000311_0001
Figure imgf000312_0001
Figure imgf000313_0001
275
Figure imgf000314_0001
Figure imgf000315_0001
Figure imgf000316_0001
Figure imgf000317_0001
Figure imgf000318_0001
Figure imgf000319_0001
Figure imgf000320_0001
Figure imgf000321_0001
Figure imgf000322_0001
Figure imgf000323_0001
Figure imgf000324_0001
Figure imgf000325_0001
Table 6. Exemplary Constructs Sequences.
Figure imgf000326_0001
Figure imgf000327_0001
Figure imgf000328_0001
Figure imgf000329_0001
Figure imgf000330_0001

Claims

CLAIMS WHAT IS CLAIMED IS: 1. An immune cell comprising a recombinant nucleic acid comprising: (a) a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, and (2) a TCR transmembrane domain, and (ii) an antigen binding domain; and (b) an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with immunoreactivity.
2. An immune cell comprising a recombinant nucleic acid comprising: (a) a sequence encoding a T cell receptor (TCR) fusion protein (TFP) comprising (i) a TCR subunit comprising (3) at least a portion of a TCR extracellular domain, and (4) a TCR transmembrane domain, and (ii) an antigen binding domain; and (b) an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with alloreactivity.
3. The immune cell of claim 1 or 2, wherein the sequence encoding the TFP and the RNAi agent or the sequence encoding the RNAi agent are contained within a same nucleic acid molecule.
4. The immune cell of claim 1 or 2, wherein the sequence encoding the TFP and the RNAi agent or the sequence encoding the RNAi agent are contained within different nucleic acid molecules.
5. The immune cell of claim 1 or 2, wherein the RNAi agent is a short hairpin RNA (shRNA).
6. The immune cell of claim 1 or 2, wherein the RNAi agent is a microRNA (miRNA).
7. The immune cell of claim 1 or 2, wherein the RNAi agent is a pri-microRNA-adapted shRNA (pri-shRNAmiR), wherein the pri-shRNAmiR is processed in the immune cell to generate a microRNA-adapted shRNA (shRNAmiR) that reduces expression of the target protein in the immune cell.
8. The immune cell of any one of claims 1-7, wherein the target protein is selected from the group consisting of beta-2 microglobulin (B2M), TRAC, TRBC1, TRBC2, CIITA, and CD70.
9. The immune cell of any one of claims 1-8, wherein the immune cell is a T cell, an NKT cell, or an NK cell.
10. The immune cell of claim 9, wherein the T cell is an alpha beta (αβ) T cell.
11. The immune cell of claim 10, wherein the αβ T cell is a CD4+ or CD8+ αβ T cell.
12. The immune cell of claim 9, wherein the T cell is a gamma delta ( ) T cell.
13. The immune cell of claim 12, wherein the γδ T cell is a Vδ 1+ Vδ 2- γδ T cell.
14. The immune cell of claim 12, wherein the γδ T cell is a Vδ 1- Vδ 2+ γδ T cell.
15. The immune cell of claim 12, wherein the γδ T cell is a Vδ 1- Vδ 2- γδ T cell.
16. The immune cell of any one of claims 1-11, wherein the immune cell comprises an RNAi agent that reduces expression of a B2M protein, and any one selected from the group consisting of an RNAi agent that reduces expression of a TRAC protein, an RNAi agent that reduces expression of a TRBC1 protein, and an RNAi agent that reduces expression of a TRBC2 protein.
17. The immune cell of any one of claims 8, 9, and 14, wherein the TCR transmembrane domain is from CD3 gamma, CD3 delta, or CD3 epsilon, and wherein the immune cell further comprises one or more sequences encoding a TCR constant domain.
18. The immune cell of claim 17, wherein the TCR constant domain is selected from the group consisting of a TCR alpha constant domain and a TCR beta constant domain.
19. The immune cell of any one of claims 8, 9, and 14, wherein the TCR transmembrane domain is from TCR alpha or TCR beta.
20. The immune cell of claim 8 or 9, wherein the TCR transmembrane domain is from TCR gamma or TCR delta, and wherein the immune cell comprises an RNAi agent that reduces expression of a B2M protein.
21. The immune cell of any one of claims 12-15, wherein the immune cell comprises a single RNAi agent that reduces expression of a B2M protein.
22. The immune cell of claim 21, wherein the TCR transmembrane domain is from CD3 gamma, CD3 delta, or CD3 epsilon.
23. The immune cell of any one of claims 7-22, wherein the shRNAmiR comprises a guide strand and a passenger strand.
24. The immune cell of any one of claims 7-23, wherein the G/C content of the shRNAmiR is between 30% and 50% or 36% and 45%.
25. The immune cell of claim 24, wherein the G/C content of the shRNAmiR is about 40%.
26. The immune cell of any one of the preceding claims, wherein the pri-shRNAmiR comprises an miR scaffold of mouse origin or of human origin.
27. The immune cell of any one of claims 7-26, wherein the pri-shRNAmiR comprises a miR scaffold comprising from 5' to 3': (a) a 5' pri-miR scaffold domain; (b) a 5' pri-miR basal stem domain; (c) a guide strand or a passenger strand; (d) a pri-miR loop domain; (e) a guide strand or a passenger strand; (f) a 3' pri-miR basal stem domain; and (g) a 3' pri-miR scaffold domain.
28. The immune cell of claim 27, wherein the pri-shRNAmiR comprises the miR scaffold comprising from 5' to 3': (a) the 5' pri-miR scaffold domain; (b) the 5' pri-miR basal stem domain; (c) the guide strand; (d) the pri-miR loop domain; (e) the passenger strand; (f) the 3' pri-miR basal stem domain; and (g) the 3' pri-miR scaffold domain.
29. The immune cell of claim 27 or 28, wherein the pri-shRNAmiR is processed by microprocessor to generate a pre-miR comprising: (a) the guide strand or the passenger strand; (b) the pre-miR loop domain; and (c) the guide strand or the passenger strand.
30. The immune cell of claim 29, wherein the pri-shRNAmiR is processed by microprocessor to generate the pre-miR comprising: (a) the guide strand; (b) the pre-miR loop domain; and (c) the passenger strand.
31. The immune cell of claim 29 or 30, wherein the pre-shRNAmiR is processed by dicer to generate the shRNAmiR.
32. The immune cell of any one of claims 7-31, wherein the pri-shRNAmiR comprises a miR-30 scaffold, a miR-15 scaffold, a miR-16 scaffold, a miR-155 scaffold, an eSIBR scaffold, a miR-22 scaffold, a miR-103 scaffold, a miR-107 scaffold, a miR- 196a2 scaffold sequence or a scaffold sequence from the miR-106a~363 cluster of mouse origin or human origin, or a variant thereof.
33. The immune cell of claim 32, wherein the miR-30 scaffold is a miR-30a scaffold.
34. The immune cell of claim 32, wherein the pri-shRNAmiR comprises the miR-155 scaffold.
35. The immune cell of claim 34, wherein the pri-shRNAmiR scaffold is based on murine miR-155 scaffold AY096003.1.
36. The immune cell of claim 35, wherein the pri-shRNAmiR comprises an enhanced synthetic inhibitory BIC/miR-155 RNA (eSIBR) scaffold.
37. The immune cell of any one of claims 26-36, wherein the miR scaffold comprises a U at position -14 and a G at position -13 relative to a 5’ microprocessor cleavage site.
38. The immune cell of any one of claims 26-37, wherein the miR scaffold comprises a CNNC motif beginning at positions +16 +17 +18 or +19 relative to a 3' microprocessor cleavage site.
39. The immune cell of any one of claims 27-38, wherein: (a) the 5' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:161; (c) the pri-miR loop domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:164.
40. The immune cell of claim 39, wherein: (a) the 5' pri-miR scaffold domain comprises the nucleic acid sequence of SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises the nucleic acid sequence of SEQ ID NO:161; (c) the pri-miR loop domain comprises the nucleic acid sequence of SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises the nucleic acid sequence of SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises the nucleic acid sequence of SEQ ID NO:164.
41. The immune cell of any one of claims 27-38, wherein the guide strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:284; the passenger strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:286, or a combination thereof.
42. The immune cell of any one of claims 27-38, wherein the guide strand comprises the nucleic acid sequence of SEQ ID NO:284; the passenger strand comprises the nucleic acid sequence of SEQ ID NO:286, or a combination thereof.
43. The immune cell of any one of claims 27-38, wherein the guide strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:284; the pre- miR loop domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:285; the passenger strand comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:286, or any combination thereof.
44. The immune cell of any one of claims 27-38, wherein the guide strand comprises the nucleic acid sequence of SEQ ID NO:284; the pre-miR loop domain comprises the nucleic acid sequence of SEQ ID NO:285; the passenger strand comprises the nucleic acid sequence of SEQ ID NO:286, or any combination thereof.
45. The immune cell of any one of claims 7-44, wherein the sequence encoding the pri- shRNAmiR is located within an intron.
46. The immune cell of any one of claims 7-45, wherein the sequence encoding the pri- shRNAmiR is located within a promoter.
47. The immune cell of claim 45 or 46, wherein the sequence encoding the pri-shRNAmiR is located within an intron within a promoter.
48. The immune cell of any one of claims 7-47, wherein the sequence encoding the pri- shRNAmiR is located within a 5’ UTR or a 3’ UTR.
49. The immune cell of any one of claims 23-48, wherein the pri-shRNAmiR is at least about 50 nucleotides in length.
50. The immune cell of any one of claims 23-49, wherein the pri-shRNAmiR is at most about 500 nucleotides in length.
51. The immune cell of any one of claims 23-50, wherein the pri-shRNAmiR is from about 100 to about 300 nucleotides in length.
52. The immune cell of any one of claims 23-51, wherein the pri-shRNAmiR is from about 120 to about 200 nucleotides in length.
53. The immune cell of any one of claims 23-52, wherein the guide strand is 15-25 nucleotides in length.
54. The immune cell of claim 53, wherein the guide strand is 20-25 nucleotides in length.
55. The immune cell of any one of claims 23-54, wherein the passenger strand is 15-25 nucleotides in length.
56. The immune cell of claim 55, wherein the passenger strand is 19-22 nucleotides in length.
57. The immune cell of any one of claims 23-56, wherein the guide strand is longer than the passenger strand.
58. The immune cell of claim 57, wherein the guide strand is two nucleotides longer than the passenger strand.
59. The immune cell of any one of claims 23-58, wherein the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the passenger sequence.
60. The immune cell of claim 59, wherein the guide strand comprises two mismatches with the passenger strand.
61. The immune cell of claim 60, wherein the guide strand comprises two mismatches with the passenger strand separated by three nucleotides.
62. The immune cell of any one of claims 23-61, wherein the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the target sequence.
63. The immune cell of any one of claims 1-62, wherein the target protein is B2M.
64. The immune cell of claim 63, wherein cell surface expression of B2M is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
65. The immune cell of claim 63 or 64, wherein expression of MHC class I molecules is reduced on the cell surface by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
66. The immune cell of any one of claims 63-65, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:165.
67. The immune cell of any one of claims 63-66, wherein the passenger strand comprises a nucleic acid sequence of SEQ ID NO:166.
68. The immune cell of any one of claims 63-66, wherein the passenger strand comprises a nucleic acid sequence of SEQ ID NO:286.
69. The immune cell of any one of claims 63-68, wherein the guide strand comprises a nucleic acid sequence of SEQ ID NO:167.
70. The immune cell of any one of claims 63-68, wherein the guide strand comprises a nucleic acid sequence of SEQ ID NO:284.
71. The immune cell of any one of claims 63-70, wherein the shRNAmiR comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:168.
72. The immune cell of claim 71, wherein the shRNAmiR comprises a nucleic acid sequence of SEQ ID NO:168.
73. The immune cell of any one of claims 63-72, wherein the immune cell comprises a functional disruption of an endogenous TCR.
74. The immune cell of claim 73, wherein the functional disruption of an endogenous TCR is a disruption of one or more of TRAC, TRBC1, or TRBC2.
75. The immune cell of any one of claims 1-62, wherein the target protein is TRAC.
76. The immune cell of claim 75, wherein cell surface expression of TRAC is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
77. The immune cell of claim 75 or 76, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:169.
78. The immune cell of any one of claims 1-62, wherein the target protein is TRBC1.
79. The immune cell of claim 78, wherein cell surface expression of TRBC1 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
80. The immune cell of claim 78 or 79, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:173.
81. The immune cell of any one of claims 1-62, wherein the target protein is TRBC2.
82. The immune cell of claim 81, wherein cell surface expression of TRBC2 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
83. The immune cell of claim 81 or 82, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:177.
84. The immune cell of any one of claims 1-62, wherein the target protein is CIITA.
85. The immune cell of claim 84, wherein cell surface expression of CIITA is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
86. The immune cell of claim 84 or 85, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:181.
87. The immune cell of any one of claims 1-62, wherein the target protein is CD70.
88. The immune cell of claim 87, wherein cell surface expression of CD70 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
89. The immune cell of claim 87 or 88, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:191.
90. The immune cell of any one of the preceding claims, wherein the TCR subunit further comprises an intracellular domain.
91. The immune cell of any one of the preceding claims, wherein the TFP functionally interacts with an endogenous TCR complex when expressed in a T cell.
92. The immune cell of any one of the preceding claims, wherein the TCR intracellular domain comprises a stimulatory domain from an intracellular signaling domain of CD3 gamma, CD3 delta, or CD3 epsilon.
93. The immune cell of any one of claims 90-92, wherein the TCR intracellular domain comprises an intracellular domain from TCR alpha, TCR beta, TCR gamma, or TCR delta.
94. The immune cell of any one of any one of the preceding claims, wherein the antigen binding domain is connected to the TCR extracellular domain by a linker sequence.
95. The immune cell of claim 94, wherein the linker is 120 amino acids in length or less.
96. The immune cell of claim 94 or 95, wherein the linker sequence comprises (G4S)n, wherein G is glycine, S is serine, and n is an integer from 1 to 10.
97. The immune cell of claim 96, wherein n is an integer from 1 to 4.
98. The immune cell of any one of claims 90-97, wherein at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit.
99. The immune cell of claim 98, wherein all three of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit.
100. The immune cell of any one of the preceding claims, wherein the immune cell further comprises one or more sequences encoding a TCR constant domain selected from the group consisting of a TCR alpha constant domain, a TCR beta constant domain, a TCR gamma constant domain, and a TCR delta constant domain.
101. The immune cell of claim 99, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 epsilon.
102. The immune cell of claim 99, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 delta.
103. The immune cell of claim 99, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 gamma.
104. The immune cell of any one of claims 101-103, wherein the immune cell further comprises: (a) a sequence encoding a TCR gamma constant domain and a TCR delta constant domain or (b) a sequence encoding a TCR alpha constant domain and a TCR beta constant domain.
105. The immune cell of claim 104, wherein the TCR alpha and TCR beta constant domains are murine.
106. The immune cell of claim 104, wherein the sequence encoding the TCR gamma constant domain further encodes a TCR gamma variable domain, thereby encoding a full TCR gamma domain.
107. The immune cell of claim 106, wherein the full TCR gamma domain is gamma 9 or gamma 4.
108. The immune cell of any one of claims 104 and 106-107, wherein the sequence encoding the TCR delta constant domain further encodes a TCR delta variable domain, thereby encoding a full TCR delta domain.
109. The immune cell acid of claim 108, wherein the full TCR delta domain is delta 2 or delta 1.
110. The immune cell of claim 99, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR alpha.
111. The immune cell of claim 110, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR alpha.
112. The immune cell of claim 110 or 111, wherein the constant domain of TCR alpha is murine.
113. The immune cell of any one of claims 110-112, wherein the immune cell further comprises a sequence encoding a TCR beta constant domain.
114. The immune cell of claim 113, wherein the TCR beta constant domain is murine.
115. The immune cell of claim 99, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR beta.
116. The immune cell of claim 115, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR beta.
117. The immune cell of claim 115 or 116, wherein the constant domain of TCR beta is murine.
118. The immune cell of any one of claims 115-117, wherein the immune cell further comprises a sequence encoding a TCR alpha constant domain.
119. The immune cell of claim 118, wherein the TCR alpha constant domain is murine.
120. The immune cell of claim 99, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR gamma.
121. The immune cell of claim 120, wherein the immune cell further comprises a sequence encoding a TCR delta constant domain.
122. The immune cell of claim 99, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR delta.
123. The immune cell of claim 122, wherein the immune cell further comprises a sequence encoding a TCR gamma constant domain.
124. The immune cell of any one of claims 104, 105, 113, 114, 118, 119, 121, and 123, wherein the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain further encodes a second antigen binding domain that is operatively linked to the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain.
125. The immune cell of claim 124, wherein the second antigen binding domain is same as or different from the antigen binding domain or ligand binding domain of the TFP.
126. The immune cell of any of the preceding claims, wherein the recombinant nucleic acid molecule further comprises the one or more sequences encoding a TCR constant domain.
127. The immune cell of claim 126, wherein the encoded TFP and the encoded TCR constant domains are operatively linked by a second linker sequence.
128. The immune cell of claim 127, wherein the second linker comprises a protease cleavage site.
129. The immune cell of claim 128, wherein the protease cleavage site is a 2A cleavage site.
130. The immune cell of claim 129, wherein the 2A protease cleavage site is a T2A cleavage site or a P2A cleavage site.
131. The immune cell of any one of the preceding claims, wherein the antigen binding domain is an antibody or a fragment thereof.
132. The immune cell of claim 131, wherein the antigen binding domain is a camelid antibody or a binding fragment thereof.
133. The immune cell of claim 131, wherein the antigen binding domain is a murine antibody or a binding fragment thereof.
134. The immune cell of claim 131, wherein the antigen binding domain is a human or humanized antibody or a binding fragment thereof.
135. The immune cell of any one of claims 131-134, wherein the antigen binding domain is a single-chain variable fragment (scFv) or a single domain antibody (sdAb) domain.
136. The immune cell of claim 135, wherein the sdAb is a VHH.
137. The immune cell of any one of the preceding claims, wherein the antigen binding domain is selected from the group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, anti-MUC16 binding domain, an anti-Nectin-4 binding domain, an anti-GPC3 binding domain, and an anti-TROP-2 binding domain.
138. The immune cell of claim 137, wherein the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:60, a CDR2 of SEQ ID NO:61, and a CDR3 of SEQ ID NO:62.
139. The immune cell of claim 137, wherein the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:63, a CDR2 of SEQ ID NO:64, and a CDR3 of SEQ ID NO:65.
140. The immune cell of claim 137, wherein the anti-MSLN binding domain comprises a sequence with at least about 80% sequence identity to a sequence of SEQ ID NO:69, or SEQ ID NO:70.
141. The immune cell of claim 137, wherein the anti-CD19 binding domain comprises a light chain CDR1 of SEQ ID NO:73, a CDR2 of SEQ ID NO:75, and a CDR3 of SEQ ID NO:77.
142. The immune cell of claim 137, wherein the anti-CD19 binding domain comprises a heavy chain CDR1 of SEQ ID NO:79, a CDR2 of SEQ ID NO:81, and a CDR3 of SEQ ID NO:83.
143. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:88, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:90.
144. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:92, a CDR2 of SEQ ID NO:93, and a CDR3 of SEQ ID NO:94.
145. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:96, a CDR2 of SEQ ID NO:97, and a CDR3 of SEQ ID NO:98.
146. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:100, a CDR2 of SEQ ID NO:101, and a CDR3 of SEQ ID NO:102.
147. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:104, a CDR2 of SEQ ID NO:105, and a CDR3 of SEQ ID NO:106.
148. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:108, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:110.
149. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:112, a CDR2 of SEQ ID NO:113, and a CDR3 of SEQ ID NO:114.
150. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:116, a CDR2 of SEQ ID NO:117, and a CDR3 of SEQ ID NO:118.
151. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:120, a CDR2 of SEQ ID NO:121, and a CDR3 of SEQ ID NO:122.
152. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:361, a CDR2 of SEQ ID NO:362, and a CDR3 of SEQ ID NO:363.
153. The immune cell of claim 137, wherein the anti-CD70 binding domain comprises a light chain CDR1 of SEQ ID NO:365, a CDR2 of SEQ ID NO:366, and a CDR3 of SEQ ID NO:367.
154. The immune cell of claim 137, wherein the anti-CD70 binding domain comprise a heavy chain variable (VH) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:364.
155. The immune cell of claim 137, wherein the anti-CD70 binding domain comprise a light chain variable (VL) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:368.
156. The immune cell of any one of the preceding claims, wherein the cell is a T cell, and wherein the expressed TFP functionally incorporates into a TCR complex of the T cell.
157. The immune cell of any one of the preceding claims, wherein the cell is a gamma delta (γδ) T cell, and wherein the expressed TFP functionally incorporates into a γδ TCR complex of the γδ T cell.
158. The immune cell of any one of the preceding claims, wherein the RNAi agent or the sequence encoding the RNAi agent comprises the sequence of SEQ ID NO:185.
159. The immune cell of any one of the preceding claims, wherein the RNAi agent or the sequence encoding the RNAi agent comprises the sequence of SEQ ID NO:186.
160. The immune cell of any one of the preceding claims, wherein the RNAi agent or the sequence encoding the RNAi agent comprises the sequence of SEQ ID NO:187.
161. The immune cell of any one of the preceding claims, wherein the RNAi agent or the sequence encoding the RNAi agent is operably linked to the sequence of SEQ ID NO:188.
162. The immune cell of any one of the preceding claims, wherein the RNAi agent or the sequence encoding the RNAi agent is operably linked to the sequence of SEQ ID NO:189.
163. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid comprises the sequence of SEQ ID NO:190.
164. The immune cell of any one of the preceding claims, wherein a T cell expressing the TFP inhibits tumor growth when expressed in a T cell.
165. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence comprising: (i) a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (ii) a CSF2RA signal peptide, a CD19 binder light chain, a Whitlow linker, a CD19 binder heavy chain, an mmTRAC, a GSG-P2A sequence, a CSF2RA signal peptide, a CD19 binder light chain, a Whitlow linker, a CD19 binder heavy chain, an mmTRBC, or any combination thereof; (iii) a CSF2RA signal peptide, an mmTRAC, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (iv) a CSF2RA signal peptide, an MSLN binder, an mmTRAC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an mmTRBC, or any combination thereof; (v) a CSF2RA signal peptide, an mmTRAC PRT, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (vi) a CSF2RA signal peptide, an MSLN binder, an mmTRAC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an mmTRBC, or any combination thereof; (vii) a CSF2RA signal peptide, an mmTRAC, a GSG-T2A sequence, a CSF2RA signal peptide, an mmTRBC, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (viii) a CSF2RA signal peptide, a tEGFR, or any combination thereof; (ix) a CSF2RA signal peptide, an MSLN binder, an A3G4SLE linker, a CD3e, or any combination thereof; (x) a CSF2RA signal peptide, an MSLN binder, a TRDC, a furin cleavage sequence, a GSG-P2A sequence, a CSF2RA signal peptide, an MSLN binder, a TRGC1, or any combination thereof; or (xi) a CSF2RA signal peptide, an MSLN binder, an A3(G4S) linker, a CD3e, or any combination thereof.
166. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence comprising, from N-terminal to C-terminal,: (i) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (ii) a CSF2RA signal peptide operatively linked to a CD19 binder light chain operatively linked to a Whitlow linker operatively linked to a CD19 binder heavy chain operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to a CD19 binder light chain operatively linked to a Whitlow linker operatively linked to a CD19 binder heavy chain operatively linked to an mmTRBC, or any combination thereof; (iii) a CSF2RA signal peptide operatively linked to an mmTRAC operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (iv) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRBC, or any combination thereof; (v) a CSF2RA signal peptide operatively linked to an mmTRAC PRT operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (vi) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRAC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an mmTRBC, or any combination thereof; (vii) a CSF2RA signal peptide operatively linked to an mmTRAC operatively linked to a GSG-T2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an mmTRBC operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (viii) a CSF2RA signal peptide operatively linked to a tEGFR, or any combination thereof; (ix) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3G4SLE linker operatively linked to a CD3e, or any combination thereof; (x) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to a TRDC operatively linked to a furin cleavage sequence operatively linked to a GSG-P2A sequence operatively linked to a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to a TRGC1, or any combination thereof; or (xi) a CSF2RA signal peptide operatively linked to an MSLN binder operatively linked to an A3(G4S) linker operatively linked to a CD3e or any combination thereof.
167. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence comprising: (i) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (ii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (iii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (iv) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (v) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (vi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (vii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (viii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:228, or any combination thereof; (ix) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (x) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:243, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:229, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:21, or any combination thereof; or (xi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214, an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof.
168. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence comprising, from N-terminal to C-terminal,: (i) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (ii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:85 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:227 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:87 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (iii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (iv) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (v) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (vi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209, or any combination thereof; (vii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:207 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:203 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:209 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (viii) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:228, or any combination thereof; (ix) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof; (x) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:243 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:229 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:208 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:21, or any combination thereof; or (xi) an amino acid sequence having at least 70% sequence identity to SEQ ID NO:201 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:69 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:214 operatively linked to an amino acid sequence having at least 70% sequence identity to SEQ ID NO:258, or any combination thereof.
169. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence comprising: (i) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (ii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:85, the sequence of SEQ ID NO:227, the sequence of SEQ ID NO:87, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:85, the sequence of SEQ ID NO:227, the sequence of SEQ ID NO:87, the sequence of SEQ ID NO:209, or any combination thereof; (iii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (iv) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:209, or any combination thereof; (v) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (vi) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:209, or any combination thereof; (vii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:207, the sequence of SEQ ID NO:203, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:209, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (viii) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:228, or any combination thereof; (ix) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof; (x) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:243, the sequence of SEQ ID NO:229, the sequence of SEQ ID NO:208, the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:21, or any combination thereof; or (xi) the sequence of SEQ ID NO:201, the sequence of SEQ ID NO:69, the sequence of SEQ ID NO:214, the sequence of SEQ ID NO:258, or any combination thereof.
170. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence comprising from N-terminal to C-terminal: (i) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (ii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:85 operatively linked to the sequence of SEQ ID NO:227 operatively linked to the sequence of SEQ ID NO:87 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:85 operatively linked to the sequence of SEQ ID NO:227 operatively linked to the sequence of SEQ ID NO:87 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (iii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (iv) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (v) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (vi) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:209, or any combination thereof; (vii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:207 operatively linked to the sequence of SEQ ID NO:203 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:209 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (viii) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:228, or any combination thereof; (ix) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof; (x) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:243 operatively linked to the sequence of SEQ ID NO:229 operatively linked to the sequence of SEQ ID NO:208 operatively linked to the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:21, or any combination thereof; or (xi) the sequence of SEQ ID NO:201 operatively linked to the sequence of SEQ ID NO:69 operatively linked to the sequence of SEQ ID NO:214 operatively linked to the sequence of SEQ ID NO:258, or any combination thereof.
171. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid comprises: (i) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:282, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:283, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:289, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:291, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (ii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:293, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:294, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:295, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:296, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:297, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (iii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:299, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:300, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:287, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:301, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:302, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:303, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:304, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:307, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:308, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:309, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:310, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (iv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:312, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:283, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:313, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:314, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:316, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:319, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:321, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (v) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:324, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:325, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:326, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:327, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:328, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (vi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:336, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:337, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:338, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:339, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:340, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (vii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:344, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:345, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:346, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:305, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:347, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:348, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (viii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:350, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:351, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:352, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:353, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:354, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (ix) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:356, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:357, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:358, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:359, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:360, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (x) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:375, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:377, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:378, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:379, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:380, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:381, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:383, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xiii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:385, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:386, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xiv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:388, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:389, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:379, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:390, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:381, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:391, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:393, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:394, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xvi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:185, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:187, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:396, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:397, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xvii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:342, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:186, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:343, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:399, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:400, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xviii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:402, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:403, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:404, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xix) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:406, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:407, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:408, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xx) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:410, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:411, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:412, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:414, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:415, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:290, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:416, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:418, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:419, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:420, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:423, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:424, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxiii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:426, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:427, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:428, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:429, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:430, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxiv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:432, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:433, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:434, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:435, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:436, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxv) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:438, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:439, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:440, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:421, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:422, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:441, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:442, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxvi) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:444, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:445, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:447, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:448, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxvii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:450, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:451, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:452, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:453, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:168, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; (xxviii) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:455, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:456, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:446, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:457, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:284, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:285, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:286, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof; or (xxix) a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:189, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:323, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:330, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:288, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:331, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:315, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:306, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:332, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:317, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:318, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:333, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:320, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:334, a nucleic acid sequence having at least 50% sequence identity to SEQ ID NO:292, or any combination thereof.
172. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid comprises: (i) the sequence of SEQ ID NO:282, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:283, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:289, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:291, the sequence of SEQ ID NO:292, or any combination thereof; (ii) the sequence of SEQ ID NO:293, the sequence of SEQ ID NO:294, the sequence of SEQ ID NO:295, the sequence of SEQ ID NO:296, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:297, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:292, or any combination thereof; (iii) the sequence of SEQ ID NO:299, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:300, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:287, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:301, the sequence of SEQ ID NO:302, the sequence of SEQ ID NO:303, the sequence of SEQ ID NO:304, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:307, the sequence of SEQ ID NO:308, the sequence of SEQ ID NO:309, the sequence of SEQ ID NO:310, the sequence of SEQ ID NO:292, or any combination thereof; (iv) the sequence of SEQ ID NO:312, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:283, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:313, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:314, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:316, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:319, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:321, the sequence of SEQ ID NO:292, or any combination thereof; (v) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:324, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:325, the sequence of SEQ ID NO:326, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:327, the sequence of SEQ ID NO:328, the sequence of SEQ ID NO:292, or any combination thereof; (vi) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:336, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:337, the sequence of SEQ ID NO:338, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:339, the sequence of SEQ ID NO:340, the sequence of SEQ ID NO:292, or any combination thereof; (vii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:344, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:345, the sequence of SEQ ID NO:346, the sequence of SEQ ID NO:305, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:347, the sequence of SEQ ID NO:348, the sequence of SEQ ID NO:292, or any combination thereof; (viii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:350, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:351, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:352, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:353, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:354, the sequence of SEQ ID NO:292, or any combination thereof; (ix) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:356, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:357, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:358, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:359, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:360, the sequence of SEQ ID NO:292, or any combination thereof; (x) the sequence of SEQ ID NO:375, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:292, or any combination thereof; (xi) the sequence of SEQ ID NO:377, the sequence of SEQ ID NO:378, the sequence of SEQ ID NO:379, the sequence of SEQ ID NO:380, the sequence of SEQ ID NO:381, the sequence of SEQ ID NO:292, or any combination thereof; (xii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:383, the sequence of SEQ ID NO:292, or any combination thereof; (xiii) the sequence of SEQ ID NO:385, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:386, the sequence of SEQ ID NO:292, or any combination thereof; (xiv) the sequence of SEQ ID NO:388, the sequence of SEQ ID NO:389, the sequence of SEQ ID NO:379, the sequence of SEQ ID NO:390, the sequence of SEQ ID NO:381, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:391, the sequence of SEQ ID NO:292, or any combination thereof; (xv) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:393, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:394, the sequence of SEQ ID NO:292, or any combination thereof; (xvi) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:185, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:187, the sequence of SEQ ID NO:396, the sequence of SEQ ID NO:397, the sequence of SEQ ID NO:292, or any combination thereof; (xvii) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:342, the sequence of SEQ ID NO:186, the sequence of SEQ ID NO:343, the sequence of SEQ ID NO:399, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:400, the sequence of SEQ ID NO:292, or any combination thereof; (xviii) the sequence of SEQ ID NO:402, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:403, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:404, the sequence of SEQ ID NO:292, or any combination thereof; (xix) the sequence of SEQ ID NO:406, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:407, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:408, the sequence of SEQ ID NO:292, or any combination thereof; (xx) the sequence of SEQ ID NO:410, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:411, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:412, the sequence of SEQ ID NO:292, or any combination thereof; (xxi) the sequence of SEQ ID NO:414, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:415, the sequence of SEQ ID NO:290, the sequence of SEQ ID NO:416, the sequence of SEQ ID NO:292, or any combination thereof; (xxii) the sequence of SEQ ID NO:418, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:419, the sequence of SEQ ID NO:420, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:423, the sequence of SEQ ID NO:424, the sequence of SEQ ID NO:292, or any combination thereof; (xxiii) the sequence of SEQ ID NO:426, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:427, the sequence of SEQ ID NO:428, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:429, the sequence of SEQ ID NO:430, the sequence of SEQ ID NO:292, or any combination thereof; (xxiv) the sequence of SEQ ID NO:432, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:433, the sequence of SEQ ID NO:434, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:435, the sequence of SEQ ID NO:436, the sequence of SEQ ID NO:292, or any combination thereof; (xxv) the sequence of SEQ ID NO:438, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:439, the sequence of SEQ ID NO:440, the sequence of SEQ ID NO:421, the sequence of SEQ ID NO:422, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:441, the sequence of SEQ ID NO:442, the sequence of SEQ ID NO:292, or any combination thereof; (xxvi) the sequence of SEQ ID NO:444, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:445, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:447, the sequence of SEQ ID NO:448, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292, or any combination thereof; (xxvii) the sequence of SEQ ID NO:450, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:451, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:452, the sequence of SEQ ID NO:453, the sequence of SEQ ID NO:168, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292; or (xxviii) the sequence of SEQ ID NO:455, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:456, the sequence of SEQ ID NO:446, the sequence of SEQ ID NO:457, the sequence of SEQ ID NO:284, the sequence of SEQ ID NO:285, the sequence of SEQ ID NO:286, the sequence of SEQ ID NO:292, or any combination thereof; or (xxix) the sequence of SEQ ID NO:189, the sequence of SEQ ID NO:323, the sequence of SEQ ID NO:330, the sequence of SEQ ID NO:288, the sequence of SEQ ID NO:331, the sequence of SEQ ID NO:315, the sequence of SEQ ID NO:306, the sequence of SEQ ID NO:332, the sequence of SEQ ID NO:317, the sequence of SEQ ID NO:318, the sequence of SEQ ID NO:333, the sequence of SEQ ID NO:320, the sequence of SEQ ID NO:334, the sequence of SEQ ID NO:292, or any combination thereof.
173. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence having at least 70% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264.
174. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264.
175. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:2-15, 65-68, 71, 159, 192-194, 198, 199, and 221-224.
176. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:2-15, 65-68, 71, 159, 192-194, 198, 199, and 221-224.
177. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:230-241 and 269-281.
178. The immune cell of any one of the preceding claims, wherein the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:230-241 and 269-281.
179. A recombinant nucleic acid of any one of the preceding claims.
180. The recombinant nucleic acid of claim 179, further comprising a leader sequence.
181. The recombinant nucleic acid of claim 179 or 180, further comprising a promoter sequence.
182. The recombinant nucleic acid of any one of claims 179-181, further comprising a sequence encoding a poly(A) tail.
183. The recombinant nucleic acid of any one of claims 179-182, further comprising a 3’UTR sequence.
184. The recombinant nucleic acid of any one of claims 179-183 comprising the sequence of SEQ ID NO:190.
185. The recombinant nucleic acid of any one of claims 179-184, wherein the recombinant nucleic acid encodes an amino acid sequence having at least 70% sequence identity to any one sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264.
186. The recombinant nucleic acid of any one of claims 179-185, wherein the recombinant nucleic acid encodes an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 195, 200, 204, 206, 210, 211, 215-220, 225, 226, 242, 244-252, 254, 257, 259, and 261-264.
187. The recombinant nucleic acid of any one of claims 179-186, wherein the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group consisting of SEQ ID NO:2-15, 65-68, 71, 159, 192- 194, 198, 199, and 221-224.
188. The recombinant nucleic acid of any one of claims 179-187, wherein the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:2- 15, 65-68, 71, 159, 192-194, 198, 199, and 221-224.
189. The recombinant nucleic acid of any one of claims 179-188, wherein the recombinant nucleic acid comprises a sequence having at least 50% sequence identity to any one sequence selected from the group selected from the group consisting of SEQ ID NO:230- 241 and 269-281.
190. The recombinant nucleic acid of any one of claims 179-189, wherein the recombinant nucleic acid comprises a sequence selected from the group consisting of SEQ ID NO:230- 241 and 269-281.
191. A vector comprising the recombinant nucleic acid of any one of the preceding claims.
192. The vector of claim 191, wherein the vector is selected from the group consisting of a DNA, an RNA, a plasmid, a lentivirus vector, adenoviral vector, an adeno-associated viral vector (AAV), a Rous sarcoma viral (RSV) vector, and a retrovirus vector.
193. The vector of claim 191 or 192, wherein the vector is an lentiviral vector.
194. The vector of any one of claims 191-193, further comprising a promoter.
195. A pharmaceutical composition comprising: (a) the immune cell of any one of claims 1-178; and (b) a pharmaceutically acceptable carrier.
196. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 195, wherein the administering is effective to treat cancer in the subject.
197. The method of claim 196, wherein less cytokines are released in the subject compared to a subject administered an effective amount of an immune cell not comprising the pri- shRNAmiR.
198. The method of claim 196 or 197, wherein the cancer is a solid cancer, a lymphoma or a leukemia.
199. The method of any one of claims 196-198, wherein the cancer is selected from the group consisting of renal cell carcinoma, breast cancer, lung cancer, ovarian cancer, prostate cancer, colon cancer, cervical cancer, brain cancer, liver cancer, pancreatic cancer, kidney cancer, and stomach cancer.
200. The method of any one of claims 196-199, wherein less cytokines are released in the subject compared to a subject administered an effective amount of an autologous T cell expressing the TFP of any one of claims 1, 2, and 90-103 and not expressing the shRNAmiR.
201. The method of any one of claims 196-200, wherein the method does not induce graft versus host disease.
202. The method of any one of claims 196-201, wherein the subject has a reduced risk of developing graft versus host disease compared to a subject administered an effective amount of an autologous T cell expressing the TFP of any one of claims 1, 2, and 90-103 and not expressing the shRNAmiR.
203. An engineered RNAi agent comprising a pri-microRNA-adapted shRNA (pri- shRNAmiR) or a sequence encoding the pri-shRNAmiR, wherein the pri-shRNAmiR is processed in an immune cell to generate a microRNA- adapted shRNA (shRNAmiR) that reduces expression of a target protein in the immune cell; and wherein the target protein is selected from the group consisting of B2M, TRAC, TRBC1, TRBC2, CIITA, and CD70.
204. The engineered RNAi agent of claim 203, wherein the shRNAmiR comprises a guide strand and a passenger strand.
205. The engineered RNAi agent of claim 203 or 204, wherein the G/C content of the shRNAmiR is between 30% and 50% or 36% and 45%.
206. The engineered RNAi agent of any one of claims 205, wherein the G/C content of the shRNAmiR is about 40%.
207. The engineered RNAi agent of any one of claims 203-206, wherein the pri-shRNAmiR comprises an miR scaffold of mouse origin or human origin.
208. The engineered RNAi agent of any one of claims 203-207, wherein the pri-shRNAmiR comprises a miR scaffold comprising from 5' to 3': (a) a 5' pri-miR scaffold domain; (b) a 5' pri-miR basal stem domain; (c) a guide strand or a passenger strand; (d) a pri-miR loop domain; (e) a guide strand or a passenger strand; (f) a 3' pri-miR basal stem domain; and (g) a 3' pri-miR scaffold domain.
209. The engineered RNAi agent of any one of claims 203-208, wherein the pri-shRNAmiR comprises the miR scaffold comprising from 5' to 3': (a) the 5' pri-miR scaffold domain; (b) the 5' pri-miR basal stem domain; (c) the guide strand; (d) the pri-miR loop domain; (e) the passenger strand; (f) the 3' pri-miR basal stem domain; and (g) the 3' pri-miR scaffold domain.
210. The engineered RNAi agent of any one of claims 203-209, wherein the pri-shRNAmiR is processed by microprocessor to generate a pre-miR comprising: (a) the guide strand or the passenger strand; (b) the pre-miR loop domain; and (c) the guide strand or the passenger strand.
211. The engineered RNAi agent of claim 210, wherein the pri-shRNAmiR is processed by microprocessor to generate the pre-miR comprising: (a) the guide strand; (b) the pre-miR loop domain; and (c) the passenger strand.
212. The engineered RNAi agent of claim 210 or 211, wherein the pre-shRNAmiR is processed by dicer to generate the shRNAmiR.
213. The engineered RNAi agent of any one of claims 203-212, wherein the pri-shRNAmiR comprises a miR-30 scaffold, a miR-15 scaffold, a miR-16 scaffold, a miR-155 scaffold, an eSIBR scaffold, a miR-22 scaffold, a miR-103 scaffold, a miR-107 scaffold, a miR- 196a2 scaffold sequence or a scaffold sequence from the miR-106a~363 cluster of mouse origin or human origin.
214. The engineered RNAi agent of any one of claims 203-213, wherein the miR-30 scaffold is a miR-30a scaffold.
215. The engineered RNAi agent of any one of claims 203-214, wherein the pri-shRNAmiR comprises the miR-155 scaffold.
216. The engineered RNAi agent of any one of claims 203-215, wherein the pri-shRNAmiR scaffold is based on murine miR-155 scaffold AY096003.1.
217. The engineered RNAi agent of any one of claims 203-216, wherein the pri-shRNAmiR comprises an enhanced synthetic inhibitory BIC/miR-155 RNA (eSIBR) scaffold.
218. The engineered RNAi agent of any one of claims 203-217, wherein the miR scaffold comprises a U at position -14 and a G at position -13 relative to a 5’ microprocessor cleavage site.
219. The engineered RNAi agent of any one of claims 203-218, wherein the miR scaffold comprises a CNNC motif beginning at positions +16 +17 +18 or +19 relative to a 3' microprocessor cleavage site.
220. The engineered RNAi agent of any one of claims 203-219, wherein: (a) the 5' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:161; (c) the pri-miR loop domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:164.
221. The engineered RNAi agent of any one of claims 203-220, wherein: (a) the 5' pri-miR scaffold domain comprises a nucleic acid sequence of SEQ ID NO:160; (b) the 5' pri-miR basal stem domain comprises a nucleic acid sequence of SEQ ID NO:161; (c) the pri-miR loop domain comprises a nucleic acid sequence of SEQ ID NO:162; (d) the 3' pri-miR basal stem domain comprises a nucleic acid sequence of SEQ ID NO:163; and (e) the 3' pri-miR scaffold domain comprises a nucleic acid sequence of SEQ ID NO:164.
222. The engineered RNAi agent of any one of claims 203-221, wherein the sequence encoding the pri-shRNAmiR is located within an intron.
223. The engineered RNAi agent of any one of claims 203-222, wherein the sequence encoding the pri-shRNAmiR is located within a promoter.
224. The engineered RNAi agent of any one of claims 203-223, wherein the sequence encoding the shRNAmiR is located within an intron within a promoter.
225. The engineered RNAi agent of any one of claims 203-224, wherein the sequence encoding the pri-shRNAmiR is located within a 5’ UTR or a 3’ UTR.
226. The engineered RNAi agent of any one of claims 203-225, wherein the pri-shRNAmiR is at least about 50 nucleotides in length.
227. The engineered RNAi agent of any one of claims 203-226, wherein the pri-shRNAmiR is at most about 500 nucleotides in length.
228. The engineered RNAi agent of any one of claims 203-227, wherein the pri-shRNAmiR is from about 100 to about 300 nucleotides in length.
229. The engineered RNAi agent of any one of claims 203-228, wherein the pri-shRNAmiR is from about 120 to about 200 nucleotides in length.
230. The engineered RNAi agent of any one of claims 203-229, wherein the guide strand is 15- 25 nucleotides in length.
231. The engineered RNAi agent of any one of claims 203-230, wherein the guide strand is 20- 25 nucleotides in length.
232. The engineered RNAi agent of any one of claims 203-231, wherein the passenger strand is 15-25 nucleotides in length.
233. The engineered RNAi agent of any one of claims 203-232, wherein the passenger strand is 19-22 nucleotides in length.
234. The engineered RNAi agent of any one of claims 203-233, wherein the guide strand is longer than the passenger strand.
235. The engineered RNAi agent of any one of claims 203-234, wherein the guide strand is two nucleotides longer than the passenger strand.
236. The engineered RNAi agent of any one of claims 203-235, wherein the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the passenger sequence.
237. The engineered RNAi agent of any one of claims 203-236, wherein the guide strand comprises two mismatches with the passenger strand.
238. The engineered RNAi agent of any one of claims 203-237, wherein the guide strand comprises two mismatches with the passenger strand separated by three nucleotides.
239. The engineered RNAi agent of any one of claims 203-238, wherein the guide strand comprises 1, 2, 3, 4, 5, or 6 mismatching nucleotides with the target sequence.
240. The engineered RNAi agent of any one of claims 203-239, wherein the target protein is B2M.
241. The engineered RNAi agent of claim 240, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:165.
242. The engineered RNAi agent of any one of claims 240-241, wherein the passenger strand comprises a nucleic acid sequence of SEQ ID NO:166.
243. The engineered RNAi agent of any one of claims 240-242, wherein the guide strand comprises a nucleic acid sequence of SEQ ID NO:167.
244. The engineered RNAi agent of any one of claims 240-243, wherein the shRNAmiR comprises a nucleic acid sequence having at least 80% sequence identity to SEQ ID NO:168.
245. The engineered RNAi agent of any one of claims 240-244, wherein the shRNAmiR comprises a nucleic acid sequence of SEQ ID NO:168.
246. The engineered RNAi agent of any one of claims 203-239, wherein the target protein is TRAC.
247. The engineered RNAi agent of claim 246, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:169.
248. The engineered RNAi agent of any one of claims 203-239, wherein the target protein is TRBC1.
249. The engineered RNAi agent of claim 248, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:173.
250. The engineered RNAi agent of any one of claims 203-239, wherein the target protein is TRBC2.
251. The engineered RNAi agent of claim 250, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:177.
252. The engineered RNAi agent of any one of claims 203-239, wherein the target protein is CIITA.
253. The engineered RNAi agent of claim 252, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:181.
254. The engineered RNAi agent of any one of claims 203-239, wherein the target protein is CD70.
255. The engineered RNAi agent of claim 254, wherein cell surface expression of CD70 is reduced by at least about 10%, about 20%, about 30%, about 40%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or up to about 99% compared to a control cell.
256. The engineered RNAi agent of claim 254 or 255, wherein the guide strand is at least 80% complementary to 15-25 contiguous nucleotides of SEQ ID NO:191.
257. The engineered RNAi agent of any one of claims 252-256, wherein the engineered RNAi agent comprises the sequence of SEQ ID NO:185.
258. The engineered RNAi agent of any one of claims 252-257, wherein the engineered RNAi agent comprises the sequence of SEQ ID NO:186.
259. The engineered RNAi agent of any one of claims 252-258, wherein the engineered RNAi agent comprises the sequence of SEQ ID NO:187.
260. The engineered RNAi agent of any one of claims 252-259, wherein the engineered RNAi agent is operably linked to the sequence of SEQ ID NO:188.
261. The engineered RNAi agent of any one of claims 252-260, wherein the engineered RNAi agent is operably linked to the sequence of SEQ ID NO:189.
262. A composition comprising the engineered RNAi agent of any one of claims 203-261 and a recombinant nucleic acid sequence encoding a T-cell receptor fusion protein (TFP) or the TFP, wherein the TFP comprises: (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, and (2) a TCR transmembrane domain, and (ii) an antigen binding domain.
263. The composition of claim 262, wherein the TCR subunit further comprises an intracellular domain.
264. The composition of any one of claims 262-263, wherein the TFP functionally interacts with an endogenous TCR complex when expressed in a T cell.
265. The composition of any one of claims 262-264, wherein the TCR intracellular domain comprises a stimulatory domain from an intracellular signaling domain of CD3 gamma, CD3 delta, or CD3 epsilon.
266. The composition of any one of claims 262-265, wherein the TCR intracellular domain comprises an intracellular domain from TCR alpha, TCR beta, TCR gamma, or TCR delta.
267. The composition of any one of claims 262-266, wherein the antigen binding domain is connected to the TCR extracellular domain by a linker sequence.
268. The composition of claim 267, wherein the linker is 120 amino acids in length or less.
269. The composition of claim 267 or 268, wherein the linker sequence comprises (G4S)n, wherein G is glycine, S is serine, and n is an integer from 1 to 10.
270. The composition of claim 269, wherein n is an integer from 1 to 4.
271. The composition of any one of claims 262-270, wherein at least two of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit.
272. The composition of claim 271, wherein all three of the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from the same TCR subunit.
273. The composition of any one of claims 262-272, wherein the immune cell further comprises one or more sequences encoding a TCR constant domain selected from the group consisting of a TCR alpha constant domain, a TCR beta constant domain, a TCR gamma constant domain, and a TCR delta constant domain.
274. The composition of claim 272, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 epsilon.
275. The composition of claim 272, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 delta.
276. The composition of claim 272, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from CD3 gamma.
277. The composition of any one of claims 274-276, wherein the immune cell further comprises: (c) a sequence encoding a TCR gamma constant domain and a TCR delta constant domain or (d) a sequence encoding a TCR alpha constant domain and a TCR beta constant domain.
278. The composition of claim 277, wherein the TCR alpha and TCR beta constant domains are murine.
279. The composition of claim 277, wherein the sequence encoding the TCR gamma constant domain further encodes a TCR gamma variable domain, thereby encoding a full TCR gamma domain.
280. The composition of claim 279, wherein the full TCR gamma domain is gamma 9 or gamma 4.
281. The composition of any one of claims 277 and 279-280, wherein the sequence encoding the TCR delta constant domain further encodes a TCR delta variable domain, thereby encoding a full TCR delta domain.
282. The composition of claim 281, wherein the full TCR delta domain is delta 2 or delta 1.
283. The composition of claim 272, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR alpha.
284. The composition of claim 283, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR alpha.
285. The composition of claim 283 or 284, wherein the constant domain of TCR alpha is murine.
286. The composition of any one of claims 283-285, wherein the immune cell further comprises a sequence encoding a TCR beta constant domain.
287. The composition of claim 286, wherein the TCR beta constant domain is murine.
288. The composition of claim 272, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain are from TCR beta.
289. The composition of claim 288, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR beta.
290. The composition of claim 288 or 289, wherein the constant domain of TCR beta is murine.
291. The composition of any one of claims 288-290, wherein the immune cell further comprises a sequence encoding a TCR alpha constant domain.
292. The composition of claim 291, wherein the TCR alpha constant domain is murine.
293. The composition of claim 272, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR gamma.
294. The composition of claim 293, wherein the immune cell further comprises a sequence encoding a TCR delta constant domain.
295. The composition of claim 272, wherein the TCR extracellular domain, the TCR transmembrane domain, and the TCR intracellular domain comprise the constant domain of TCR delta.
296. The composition of claim 295, wherein the immune cell further comprises a sequence encoding a TCR gamma constant domain.
297. The composition of any one of claims 277, 278, 286, 287, 291, 292, 294, and 296, wherein the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain further encodes a second antigen binding domain that is operatively linked to the sequence encoding the TCR alpha constant domain, the TCR beta constant domain, the TCR gamma constant domain, or the TCR delta constant domain.
298. The composition of claim 297, wherein the second antigen binding domain is same as or different from the antigen binding domain or ligand binding domain of the TFP.
299. The composition of any one of claims 262-298, wherein the recombinant nucleic acid molecule further comprises the one or more sequences encoding a TCR constant domain.
300. The composition of claim 299, wherein the encoded TFP and the encoded TCR constant domains are operatively linked by a second linker sequence.
301. The composition of claim 300, wherein the second linker comprises a protease cleavage site.
302. The composition of claim 301, wherein the protease cleavage site is a 2A cleavage site.
303. The composition of claim 302, wherein the 2A protease cleavage site is a T2A cleavage site or a P2A cleavage site.
304. The composition of any one of claims 262-303, wherein the antigen binding domain is an antibody or a fragment thereof.
305. The composition of claim 304, wherein the antigen binding domain is a camelid antibody or a binding fragment thereof.
306. The composition of claim 304, wherein the antigen binding domain is a murine antibody or a binding fragment thereof.
307. The composition of claim 304, wherein the antigen binding domain is a human or humanized antibody or a binding fragment thereof.
308. The composition of any one of claims 304-307, wherein the antigen binding domain is a single-chain variable fragment (scFv) or a single domain antibody (sdAb) domain.
309. The composition of claim 308, wherein the sdAb is a VHH.
310. The composition of any one of claims 262-309, wherein the antigen binding domain is selected from the group consisting of an anti-CD19 binding domain, an anti-B-cell maturation antigen (BCMA) binding domain, an anti-mesothelin (MSLN) binding domain, an anti-CD20 binding domain, an anti-CD70 binding domain, anti-MUC16 binding domain, an anti-Nectin-4 binding domain, an anti-GPC3 binding domain, and an anti-TROP-2 binding domain.
311. The composition of claim 310, wherein the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:60, a CDR2 of SEQ ID NO:61, and a CDR3 of SEQ ID NO:62.
312. The composition of claim 310, wherein the anti-MSLN binding domain comprises a CDR1 of SEQ ID NO:63, a CDR2 of SEQ ID NO:64, and a CDR3 of SEQ ID NO:65.
313. The composition of claim 310, wherein the anti-MSLN binding domain comprises a sequence with at least about 80% sequence identity to a sequence of SEQ ID NO:69, or SEQ ID NO:70.
314. The composition of claim 310, wherein the anti-CD19 binding domain comprises a light chain CDR1 of SEQ ID NO:73, a CDR2 of SEQ ID NO:75, and a CDR3 of SEQ ID NO:77.
315. The composition of claim 310, wherein the anti-CD19 binding domain comprises a heavy chain CDR1 of SEQ ID NO:79, a CDR2 of SEQ ID NO:81, and a CDR3 of SEQ ID NO:83.
316. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:88, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:90.
317. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:92, a CDR2 of SEQ ID NO:93, and a CDR3 of SEQ ID NO:94.
318. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:96, a CDR2 of SEQ ID NO:97, and a CDR3 of SEQ ID NO:98.
319. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:100, a CDR2 of SEQ ID NO:101, and a CDR3 of SEQ ID NO:102.
320. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:104, a CDR2 of SEQ ID NO:105, and a CDR3 of SEQ ID NO:106.
321. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:108, a CDR2 of SEQ ID NO:89, and a CDR3 of SEQ ID NO:110.
322. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:112, a CDR2 of SEQ ID NO:113, and a CDR3 of SEQ ID NO:114.
323. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:116, a CDR2 of SEQ ID NO:117, and a CDR3 of SEQ ID NO:118.
324. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:120, a CDR2 of SEQ ID NO:121, and a CDR3 of SEQ ID NO:122.
325. The composition of claim 310, wherein the anti-CD70 binding domain comprises a heavy chain CDR1 of SEQ ID NO:361, a CDR2 of SEQ ID NO:362, and a CDR3 of SEQ ID NO:363.
326. The composition of claim 310, wherein the anti-CD70 binding domain comprises a light chain CDR1 of SEQ ID NO:365, a CDR2 of SEQ ID NO:366, and a CDR3 of SEQ ID NO:367.
327. The composition of claim 310, wherein the anti-CD70 binding domain comprise a heavy chain variable (VH) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:364.
328. The composition of claim 310, wherein the anti-CD70 binding domain comprise a light chain variable (VL) domain having at least about 80% sequence identity to a sequence of SEQ ID NO:368.
329. The composition of any one of claims 262-315, wherein the cell is a T cell, and wherein the expressed TFP functionally incorporates into a TCR complex of the T cell.
330. The composition of any one of claims 262-329, wherein the cell is a gamma delta (γδ) T cell, and wherein the expressed TFP functionally incorporates into a γδ TCR complex of the γδ T cell.
331. The composition of any one of claims 262-330, wherein a T cell expressing the TFP inhibits tumor growth when expressed in a T cell.
332. The composition of any one of claims 262-331, wherein the composition comprises a recombinant nucleic acid having the sequence of SEQ ID NO:190.
333. A method of producing the immune cell of any one of claims 1-178, the method comprising: (a) delivering into the immune cell an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with immunoreactivity; and (b) transducing a sequence encoding a TFP according to any one of claims 262-332.
334. A method of producing the immune cell of any one of claims 1-178, the method comprising: (a) delivering into the immune cell an RNA interference (RNAi) agent or a sequence encoding the RNAi agent; wherein the RNAi agent reduces expression of a target protein in the immune cell, wherein the target protein is a protein associated with alloreactivity; and (b) transducing a sequence encoding a TFP according to any one of claims 262-332.
335. The method of producing the immune cell of claim 333 or 334, wherein the target protein is selected from the group consisting of beta-2 microglobulin (B2M), TRAC, TRBC1, TRBC2, CIITA, and CD70.
336. The method of producing the immune cell of any one of claims 333-335, wherein the TFP comprises: (i) a TCR subunit comprising (1) at least a portion of a TCR extracellular domain, and (2) a transmembrane domain, and (ii) an antibody domain comprising an antigen binding domain.
337. The method of producing the immune cell of any one of claims 333-336, wherein the sequence encoding the TFP further encodes a TCR constant domain.
338. The method of producing the immune cell of any one of claims 333-337, wherein the sequence encoding the TCR constant domain further encodes a second antigen binding domain that is operatively linked to the sequence encoding the TCR constant domain
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US20180251514A1 (en) * 2015-05-18 2018-09-06 TCR2 Therapeutics Inc. Compositions and methods for tcr reprogramming using fusion proteins
WO2020206248A1 (en) * 2019-04-03 2020-10-08 Precision Biosciences, Inc. Genetically-modified immune cells comprising a microrna-adapted shrna (shrnamir)

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Publication number Priority date Publication date Assignee Title
US20180251514A1 (en) * 2015-05-18 2018-09-06 TCR2 Therapeutics Inc. Compositions and methods for tcr reprogramming using fusion proteins
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