Compositions and methods for treating neoplasia

Abstract

The present disclosure provides engineered T cells comprising TCRs that specifically recognize and bind p53 R175H, and methods of using such cells for the treatment of neoplasias.

Description

[0001] COMPOSITIONS AND METHODS FOR TREATING NEOPLASIA CROSS REFERENCE This application claims the benefit of the following U.S. Provisional Application Nos.: 63 / 604,709, filed November 30, 2023; 63 / 575,241, filed April 5, 2024; and 63 / 716,389, filed November 5, 2024, the entire contents of each of which are incorporated herein by reference. BACKGROUND OF THE INVENTION Hallmarks of cancer include sustained proliferative signaling, evading growth suppressors, resisting cell death, replicative immortality, the ability to induce angiogenesis, and the potential for the invasion of other tissues and metastasis. These hallmarks can be acquired by mutations of genes that are involved in these biological processes. p53, a sequence-transcription factor encoded by the TP53 gene, is called "the guardian of the genome" because it can sense DNA damage in cells and induce DNA repair, cell-cycle arrest, and apoptosis by modulating the expression of its target genes. Once the p53 pathway has been altered, genetically damaged cells will not go into senescence or apoptosis, causing the accumulation of mutations and acquiring hallmarks of cancer. The p53 protein has an N-terminus containing transactivation domain, a DNA binding domain that binds to specific DNA sequences, and C-terminus oligomerization and regulatory domains.41.8% of cancer patients have alterations in TP53, many of which are in the DNA binding domain, as well as several other hotspots within the p53 protein. Adoptive T cell therapy (ACT) has demonstrated activity in solid tumors but requires further optimization to become more reproducibly effective. T cells engineered with T cell receptors (TCRs) that specifically target p53 have the potential to induce durable responses in patients with solid tumors. SUMMARY OF THE INVENTION The present disclosure provides engineered T cells comprising T cell receptors (TCRs) that specifically recognize and bind a p53 peptide comprising an R175H mutation ("p53 R175H"), and methods of using such cells for the treatment of neoplasias. In an aspect, the present disclosure provides an engineered cell including: a heterologous T cell receptor (TCR) that specifically binds a mutant form of p53 peptide present in a peptide:HLA complex; a CD8 co-receptor; and a switch receptor including a FAS extracellular domain fused to 41BB intracellular signaling domain or a chimeric fusion polypeptide including an IL7 receptor alpha intracellular domain or both the switch receptor incluidng a FAS extracellular domain fused to 41BB intracellular signaling domain and the chimeric fusion polypeptide including an IL7 receptor alpha intracellular domain. In another aspect, the present disclosure provides an engineered cell including: a polynucleotide encoding a heterologous T cell receptor (TCR) that specifically binds a mutant form of p53 peptide present in a peptide:HLA complex; a polynucleotide encoding a CD8 co- receptor; and a polynucleotide encoding a switch receptor including a FAS extracellular domain fused to 41BB intracellular signaling domain and / or a polynucleotide encoding a chimeric fusion polypeptide including an IL7 receptor alpha intracellular domain, where the engineered cell has decreased expression of TRAC1, TRBC1, or TRBC2. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes: a TCR α chain variable (Vα) domain inlcuding an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161- 167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes: a TCR α chain variable (Vα) domain including an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes: a TCR α chain variable (Vα) domain including an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161- 167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes: a TCR α chain variable (Vα) domain including an amino acid sequence of any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence of any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence of any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61- 67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171- 177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes a Vα including an amino acid sequence with at least 85% sequence identity to SEQ ID NO.168 and a Vβ including an amino acid sequence with at least 85% sequence identity to SEQ ID NO.178. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes a Vα including an amino acid sequence with at least 90% sequence identity to SEQ ID NO.168 and a Vβ including an amino acid sequence with at least 90% sequence identity to SEQ ID NO.178. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes a Vα including an amino acid sequence with at least 95% sequence identity to SEQ ID NO.168 and a Vβ including an amino acid sequence with at least 95% sequence identity to SEQ ID NO.178. In another aspect, the present disclosure provides a polynucleotide encoding a TCR, where the TCR includes a Vα including an amino acid sequence of SEQ ID NO.168 and a Vβ including an amino acid sequence of SEQ ID NO.178. In another aspect, the present disclosure provides a vector including the polynucleotide of any one of the above aspects, or embodiments thereof. In another aspect, the present disclosure provides a cell including the polynucleotide of any one of the above aspects, or embodiments thereof or the vector of any one of the above aspects, or embodiments thereof. In another aspect, the present disclosure provides a pharmaceutical composition including the engineered cell of any one of the above aspects, or embodiments thereof, and a pharmaceutically acceptable carrier, excipient, or diluent. In another aspect, the present disclosure provides a method of treating a neoplasia. The method involves administering the engineered cell of any one of the above aspects, or embodiments thereof, or the pharmaceutical composition of any one of the above aspects, or embodiments thereof, to a subject in need thereof. In another aspect, the present disclosure provides a method of enriching a population of genetically modified T cells expressing a FasBB fusion protein. The method involves: contacting a culture of T cells with Fas ligand; and selecting viable T cells. In another aspect, the present disclosure provides a method of killing a cancer cell presenting a p53 R175H mutant peptide on an HLA-A*02 molecule. The method involves contacting the cancer cell with an engineered T cell expressing a heterologous T cell receptor (TCR) that binds the p53 R175H mutant peptide presented on an HLA-A*02 molecule. In another aspect, the present disclosure provides a method of inhibiting or reducing tumor growth, where the tumor includes cells presenting a p53 R175H mutant peptide on an HLA-A*02 molecule. The method involves contacting the cancer tumor with engineered T cells each expressing a heterologous TCR that binds the p53 R175H mutant peptide presented on an HLA-A*02 molecule. In another aspect, the present disclosure provides a method of treating a cancer in a subject. The method involves: administering to the subject a pharmaceutically effective amount of engineered T cells each expressing a heterologous TCR that binds the p53 R175H mutant peptide presented on an HLA-A*02 molecule and a FasBB fusion protein. In any of the above aspects, or embodiments thereof, the peptide:HLA complex includes an HLA protein encoded by an HLA-A*02 allele. In any of the above aspects, or embodiments thereof, the peptide:HLA complex includes an HLA protein encoded by an HLA-A*02:01 allele. In any of the above aspects, or embodiments thereof, the extracellular binding protein includes a T cell receptor (TCR) α chain variable (Vα) region, a TCR β chain variable (Vβ) region, a T cell receptor (TCR) α chain constant (Cα) region, or a T cell receptor (TCR) β chain constant (Cβ) region In any of the above aspects, or embodiments thereof, the mutant form of p53 peptide includes an amino acid sequence HMTEVVRHC. In any of the above aspects, or embodiments thereof, the mutant form of p53 is p53 R175H. In any of the above aspects, or embodiments thereof, the Vα domain or the Vβ domain are human, humanized, or chimeric. In any of the above aspects, or embodiments thereof, the TCR is human, humanized, or chimeric. In any of the above aspects, or embodiments thereof, the cell is an immune cell, or a precursor thereof. In any of the above aspects, or embodiments thereof, the immune cell includes a T cell, a NK cell, a NK-T cell, a dendritic cell, a macrophage, a monocyte, or any combination thereof. In any of the above aspects, or embodiments thereof, the TCR includes: a TCR α chain variable (Vα) domain including an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In any of the above aspects, or embodiments thereof, the TCR includes: a TCR α chain variable (Vα) domain including an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In any of the above aspects, or embodiments thereof, the TCR includes: a TCR α chain variable (Vα) domain including an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In any of the above aspects, or embodiments thereof, the TCR includes: a TCR α chain variable (Vα) domain including an amino acid sequence of any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain including an amino acid sequence of any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region including an amino acid sequence of any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81- 87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237. In any of the above aspects, or embodiments thereof, the TCR includes a Vα including an amino acid sequence with at least 85% sequence identity to SEQ ID NO.168 and a Vβ including an amino acid sequence with at least 85% sequence identity to SEQ ID NO.178. In any of the above aspects, or embodiments thereof, the TCR includes a Vα including an amino acid sequence with at least 90% sequence identity to SEQ ID NO.168 and a Vβ including an amino acid sequence with at least 90% sequence identity to SEQ ID NO.178. In any of the above aspects, or embodiments thereof, the TCR includes a Vα including an amino acid sequence with at least 95% sequence identity to SEQ ID NO.168 and a Vβ including an amino acid sequence with at least 95% sequence identity to SEQ ID NO.178. In any of the above aspects, or embodiments thereof, the TCR includes a Vα including an amino acid sequence of SEQ ID NO. 168 and a Vβ including an amino acid sequence of SEQ ID NO.178. In any of the above aspects, or embodiments thereof, the engineered cell, further includes a genomic mutation that decreases expression of an endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), and / or T cell receptor β constant 2 (TRBC2). In any of the above aspects, or embodiments thereof, the genomic mutation that causes or contributes to decreased expression of the endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), or a T cell receptor β constant 2 (TRBC2) comprises an indel in the TRAC, TRBC1, or TRBC2 locus. In any of the above aspects, or embodiments thereof, the genomic mutation that causes or contributes to decreased expression of the endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), or T cell receptor β constant 2 (TRBC2) is a missense mutation that causes or contributes to reduced function or stability of a T cell receptor α or T cell receptor β polypeptide encoded by a genome of the cell. In any of the above aspects, or embodiments thereof, the genomic mutation that decreases expression of the endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), or a T cell receptor β constant 2 (TRBC2) results in premature termination of a T cell receptor α or T cell receptor β polypeptide encoded by the endogenous TRAC, TRBC1, or TRBC2. In any of the above aspects, or embodiments thereof, the immune cell includes a T cell, where the T cell comprises a CD4+T cell, a CD8+T cell, a CD4- CD8- double negative T cell, a γδ T cell, or any combination thereof. In any of the above aspects, or embodiments thereof: a) an α chain of the CD8 co- receptor includes an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 261; and / or b) a β chain of the CD8 co-receptor includes an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 262. In any of the above aspects, or embodiments thereof, the switch receptor includes an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 263 or 264. In any of the above aspects, or embodiments thereof, the chimeric fusion polypeptide includes an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, or 276. In any of the above aspects, or embodiments thereof, the polynucleotide encoding the heterologous TCR is inserted at a TRAC, TRBC1, or TRBC2 locus. In any of the above aspects, or embodiments thereof, the polynucleotide encoding the CD8 co-receptor is inserted at a TRAC, TRBC1, or TRBC2 locus. In any of the above aspects, or embodiments thereof, the polynucleotide encoding the FAS extracellular domain fused to 41BB intracellular signaling domain is inserted at a TRAC, TRBC1, or TRBC2 locus. In any of the above aspects, or embodiments thereof, the polynucleotide encoding the chimeric fusion polypeptide including the IL7 receptor alpha intracellular domain is inserted at a TRAC, TRBC1, or TRBC2 locus. In any of the above aspects, or embodiments thereof, the TCR specifically binds a mutant form of p53 peptide present in a peptide:HLA complex. In any of the above aspects, or embodiments thereof, the mutant form of p53 is p53 R175H. In any of the above aspects, or embodiments thereof, the mutant form of p53 includes an amino acid sequence of HMTEVVRHC. In any of the above aspects, or embodiments thereof, the nucleic acid sequence is codon optimized. In any of the above aspects, or embodiments thereof, the extracellular binding protein is human, humanized, or chimeric. In any of the above aspects, or embodiments thereof, the polynucleotide further includes a promoter. In any of the above aspects, or embodiments thereof, the promoter is a murine stem cell virus (MSCV) promoter, an elongation factor-1 alpha (EF-1α) promoter, or a Meiotic Nuclear Divisions 1 (MND1) promoter. In any of the above aspects, or embodiments thereof, the polynucleotide includes RNA, DNA, or a combination thereof. In any of the above aspects, or embodiments thereof, the vector is a lentiviral vector, a γ- retroviral vector, or an adeno-associated virus (AAV) vector. In any of the above aspects, or embodiments thereof, the pharmaceutical composition includes between about a 1:10 ratio to about a 10:1 ratio of CD4+ and CD8+ T cells. In any of the above aspects, or embodiments thereof, the neoplasia is colorectal cancer, esophageal cancer, head and neck cancer, larynx cancer, lung cancer, breast cancer, endometrial cancer, or ovarian cancer. In any of the above aspects, or embodiments thereof, the lung cancer is small cell lung cancer or squamous cell lung cancer. In any of the above aspects, or embodiments thereof, the breast cancer is triple-negative breast cancer. In any of the above aspects, or embodiments thereof, the ovarian cancer is high-grade serous ovarian cancer. In any of the above aspects, or embodiments thereof, each engineered T cell co-expresses a CD8 co-receptor. In any of the above aspects, or embodiments thereof, each engineered T cell includes a chimeric fusion polypeptide comprising an IL7 receptor alpha intracellular domain. In any of the above aspects, or embodiments thereof, each engineered T cell includes a knockout of endogenous TRAC and / or TRBC. In any of the above aspects, or embodiments thereof, the HLA*02 molecule is encoded by an HLA-A*02:01 allele. Other features and advantages of the disclosure will be apparent from the detailed description, and from the claims. Definitions Unless defined otherwise, all technical and scientific terms used herein have the meaning commonly understood by a person skilled in the art to which this invention belongs. The following references provide one of skill with a general definition of many of the terms used in this invention: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). As used herein, the following terms have the meanings ascribed to them below, unless specified otherwise. By "agent" is meant a polypeptide, polynucleotide, a cell engineered to express a heterologous polypeptide or polynucleotide, or a small compound. In some embodiments, the cell is an immune cell (e.g., T cell) that is autologous or heterologous to a subject. In one embodiment, the agent is a T cell expressing a T cell receptor that binds a p53 polypeptide comprising an R175H mutation. By "alteration" is meant a change (increase or decrease) in the expression levels, structure, or activity of a gene or polypeptide as detected by standard art known methods such as those described herein. In one embodiment, the alteration is an R175H mutation in a p53 polypeptide. As used herein, an alteration includes a 10% change in expression levels, a 25% change, a 40% change, or a 50% or greater change in expression levels. By "ameliorate" is meant decrease, suppress, attenuate, diminish, arrest, or stabilize the development or progression of a disease. In one embodiment, the disease is cancer (e.g., a cancer featuring cells comprising a p53 R175H mutation). By "antigen" is meant a moiety or molecule (e.g., polypeptide, peptide) that is capable of inducing an immune response. An antigen contains an epitope to which a binding protein of the present disclosure can specifically bind. As such, an antigen is also specifically bound by a binding protein of the present disclosure. Antigens may be, without limitation, proteins, peptides, polysaccharides, lipids, or nucleic acids. In an embodiment, the antigen comprises a R175H mutation in a p53 polypeptide sequence. By "neoantigen" is meant a newly formed antigen generated by a neoplasia as a result of a neoplasia-specific alteration. In an embodiment, the neoantigen comprises a R175H mutation in a p53 polypeptide sequence. By "binding protein" is meant a protein that specifically binds to a given target. In some embodiments, the binding protein is a T cell receptor (TCR). In some embodiments, the target of the binding protein is an antigen or a neoantigen. In an embodiment, the target of the binding protein comprises a R175H mutation in a p53 polypeptide sequence. In this disclosure, "comprises," "comprising," "containing," "having," and the like can have the meaning ascribed to them in U.S. Patent law and can mean " includes," "including," and the like; "consisting essentially of" or "consists essentially" likewise has the meaning ascribed in U.S. Patent law and the term is open-ended, allowing for the presence of more than that which is recited so long as basic or novel characteristics of that which is recited is not changed by the presence of more than that which is recited, but excludes prior art embodiments. As used herein, the term "CD8 co-receptor polypeptide," "CD8 coreceptor," or "CD8 polypeptide" generally refers to the cell surface glycoprotein CD8. CD8 is present at the cell surface as either as an CD8alpha subunit-CD8alpha subunit homodimer ("CD8aa coreceptor" or "CD8αα coreceptor" or a CD8alpha subunit-CD8beta subunit heterodimer ("CD8ab coreceptor" or "CD8αβ coreceptor"). The CD8 co-receptor assists in the function of cytotoxic T cells (CD8+) and functions through signaling via its cytoplasmic tyrosine phosphorylation pathway (Gao and Jakobsen, Immunol. Today 21:630-636, 2000; Cole and Gao, Cell. Mol. Immunol. 1:81-88, 2004). There are five (5) documented human CD8 beta chain isoforms (see UniProtKB identifier P10966) and a single documented human CD8 alpha chain isoform (see UniProtKB identifier P01732). By "CD8alpha polypeptide" or "CD8α polypeptide" is meant a polypeptide having at least about 85% amino acid sequence identity to NCBI Accession Nos. NP_001759.3 or NP_741969.1, or a fragment thereof having co-receptor activity for ligand recognition by T cell receptors when dimerized with another CD8α or a CD8β. Exemplary CD8α amino acid sequences are provided below: >NP_001759.3 T-cell surface glycoprotein CD8 alpha chain isoform 1 precursor [Homo sapiens] MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFL LYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSALSNSIMYFSHFVPVFLPAKPTTT PAPRPPTPAPTIASQPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRN RRRVCKCPRPVVKSGDKPSLSARYV >NP_741969.1 T-cell surface glycoprotein CD8 alpha chain isoform 2 precursor [Homo sapiens] MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFL LYLSQNKPKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSALSNSIMYFSHFVPVFLPAKPTTT PAPRPPTPAPTIASQPLSLRPEACRPAAGGAGNRRRVCKCPRPVVKSGDKPSLSARYV By "CD8alpha polynucleotide" or "CD8α polynucleotide" is meant a nucleic acid molecule encoding a CD8α polypeptide. Exemplary CD8alpha polynucleotide sequences are provided below: >NM_001768.7 Homo sapiens CD8 subunit alpha (CD8A), transcript variant 1, mRNA AACTTTCCCCCCTCGGCGCCCCACCGGCTCCCGCGCGCCTCCCCTCGCGCCCGAGCTTCGAGCCAAGCAG CGTCCTGGGGAGCGCGTCATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACG CCGCCAGGCCGAGCCAGTTCCGGGTGTCGCCGCTGGATCGGACCTGGAACCTGGGCGAGACAGTGGAGCT GAAGTGCCAGGTGCTGCTGTCCAACCCGACGTCGGGCTGCTCGTGGCTCTTCCAGCCGCGCGGCGCCGCC GCCAGTCCCACCTTCCTCCTATACCTCTCCCAAAACAAGCCCAAGGCGGCCGAGGGGCTGGACACCCAGC GGTTCTCGGGCAAGAGGTTGGGGGACACCTTCGTCCTCACCCTGAGCGACTTCCGCCGAGAGAACGAGGG CTACTATTTCTGCTCGGCCCTGAGCAACTCCATCATGTACTTCAGCCACTTCGTGCCGGTCTTCCTGCCA GCGAAGCCCACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGT CCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGGGCTGGACTTCGCCTG TGATATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCACTGGTTATCACCCTT TACTGCAACCACAGGAACCGAAGACGTGTTTGCAAATGTCCCCGGCCTGTGGTCAAATCGGGAGACAAGC CCAGCCTTTCGGCGAGATACGTCTAACCCTGTGCAACAGCCACTACATTACTTCAAACTGAGATCCTTCC TTTTGAGGGAGCAAGTCCTTCCCTTTCATTTTTTCCAGTCTTCCTCCCTGTGTATTCATTCTCATGATTA TTATTTTAGTGGGGGCGGGGTGGGAAAGATTACTTTTTCTTTATGTGTTTGACGGGAAACAAAACTAGGT AAAATCTACAGTACACCACAAGGGTCACAATACTGTTGTGCGCACATCGCGGTAGGGCGTGGAAAGGGGC AGGCCAGAGCTACCCGCAGAGTTCTCAGAATCATGCTGAGAGAGCTGGAGGCACCCATGCCATCTCAACC TCTTCCCCGCCCGTTTTACAAAGGGGGAGGCTAAAGCCCAGAGACAGCTTGATCAAAGGCACACAGCAAG TCAGGGTTGGAGCAGTAGCTGGAGGGACCTTGTCTCCCAGCTCAGGGCTCTTTCCTCCACACCATTCAGG TCTTTCTTTCCGAGGCCCCTGTCTCAGGGTGAGGTGCTTGAGTCTCCAACGGCAAGGGAACAAGTACTTC TTGATACCTGGGATACTGTGCCCAGAGCCTCGAGGAGGTAATGAATTAAAGAAGAGAACTGCCTTTGGCA GAGTTCTATAATGTAAACAATATCAGACTTTTTTTTTTTATAATCAAGCCTAAAATTGTATAGACCTAAA ATAAAATGAAGTGGTGAGCTTAACCCTGGAAAATGAATCCCTCTATCTCTAAAGAAAATCTCTGTGAAAC CCCTATGTGGAGGCGGAATTGCTCTCCCAGCCCTTGCATTGCAGAGGGGCCCATGAAAGAGGACAGGCTA CCCCTTTACAAATAGAATTTGAGCATCAGTGAGGTTAAACTAAGGCCCTCTTGAATCTCTGAATTTGAGA TACAAACATGTTCCTGGGATCACTGATGACTTTTTATACTTTGTAAAGACAATTGTTGGAGAGCCCCTCA CACAGCCCTGGCCTCTGCTCAACTAGCAGATACAGGGATGAGGCAGACCTGACTCTCTTAAGGAGGCTGA GAGCCCAAACTGCTGTCCCAAACATGCACTTCCTTGCTTAAGGTATGGTACAAGCAATGCCTGCCCATTG GAGAGAAAAAACTTAAGTAGATAAGGAAATAAGAACCACTCATAATTCTTCACCTTAGGAATAATCTCCT GTTAATATGGTGTACATTCTTCCTGATTATTTTCTACACATACATGTAAAATATGTCTTTCTTTTTTAAA TAGGGTTGTACTATGCTGTTATGAGTGGCTTTAATGAATAAACATTTGTAGCATCCTCTTTAATGGGTAA ACAGCA >NM_171827.4 Homo sapiens CD8 subunit alpha (CD8A), transcript variant 2, mRNA AACTTTCCCCCCTCGGCGCCCCACCGGCTCCCGCGCGCCTCCCCTCGCGCCCGAGCTTCGAGCCAAGCAG CGTCCTGGGGAGCGCGTCATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACG CCGCCAGGCCGAGCCAGTTCCGGGTGTCGCCGCTGGATCGGACCTGGAACCTGGGCGAGACAGTGGAGCT GAAGTGCCAGGTGCTGCTGTCCAACCCGACGTCGGGCTGCTCGTGGCTCTTCCAGCCGCGCGGCGCCGCC GCCAGTCCCACCTTCCTCCTATACCTCTCCCAAAACAAGCCCAAGGCGGCCGAGGGGCTGGACACCCAGC GGTTCTCGGGCAAGAGGTTGGGGGACACCTTCGTCCTCACCCTGAGCGACTTCCGCCGAGAGAACGAGGG CTACTATTTCTGCTCGGCCCTGAGCAACTCCATCATGTACTTCAGCCACTTCGTGCCGGTCTTCCTGCCA GCGAAGCCCACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCGCGTCGCAGCCCCTGT CCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGGGAACCGAAGACGTGTTTGCAAATGTCC CCGGCCTGTGGTCAAATCGGGAGACAAGCCCAGCCTTTCGGCGAGATACGTCTAACCCTGTGCAACAGCC ACTACATTACTTCAAACTGAGATCCTTCCTTTTGAGGGAGCAAGTCCTTCCCTTTCATTTTTTCCAGTCT TCCTCCCTGTGTATTCATTCTCATGATTATTATTTTAGTGGGGGCGGGGTGGGAAAGATTACTTTTTCTT TATGTGTTTGACGGGAAACAAAACTAGGTAAAATCTACAGTACACCACAAGGGTCACAATACTGTTGTGC GCACATCGCGGTAGGGCGTGGAAAGGGGCAGGCCAGAGCTACCCGCAGAGTTCTCAGAATCATGCTGAGA GAGCTGGAGGCACCCATGCCATCTCAACCTCTTCCCCGCCCGTTTTACAAAGGGGGAGGCTAAAGCCCAG AGACAGCTTGATCAAAGGCACACAGCAAGTCAGGGTTGGAGCAGTAGCTGGAGGGACCTTGTCTCCCAGC TCAGGGCTCTTTCCTCCACACCATTCAGGTCTTTCTTTCCGAGGCCCCTGTCTCAGGGTGAGGTGCTTGA GTCTCCAACGGCAAGGGAACAAGTACTTCTTGATACCTGGGATACTGTGCCCAGAGCCTCGAGGAGGTAA TGAATTAAAGAAGAGAACTGCCTTTGGCAGAGTTCTATAATGTAAACAATATCAGACTTTTTTTTTTTAT AATCAAGCCTAAAATTGTATAGACCTAAAATAAAATGAAGTGGTGAGCTTAACCCTGGAAAATGAATCCC TCTATCTCTAAAGAAAATCTCTGTGAAACCCCTATGTGGAGGCGGAATTGCTCTCCCAGCCCTTGCATTG CAGAGGGGCCCATGAAAGAGGACAGGCTACCCCTTTACAAATAGAATTTGAGCATCAGTGAGGTTAAACT AAGGCCCTCTTGAATCTCTGAATTTGAGATACAAACATGTTCCTGGGATCACTGATGACTTTTTATACTT TGTAAAGACAATTGTTGGAGAGCCCCTCACACAGCCCTGGCCTCTGCTCAACTAGCAGATACAGGGATGA GGCAGACCTGACTCTCTTAAGGAGGCTGAGAGCCCAAACTGCTGTCCCAAACATGCACTTCCTTGCTTAA GGTATGGTACAAGCAATGCCTGCCCATTGGAGAGAAAAAACTTAAGTAGATAAGGAAATAAGAACCACTC ATAATTCTTCACCTTAGGAATAATCTCCTGTTAATATGGTGTACATTCTTCCTGATTATTTTCTACACAT ACATGTAAAATATGTCTTTCTTTTTTAAATAGGGTTGTACTATGCTGTTATGAGTGGCTTTAATGAATAA ACATTTGTAGCATCCTCTTTAATGGGTAAACAGCA >NM_001145873.1 Homo sapiens CD8 subunit alpha (CD8A), transcript variant 3, mRNA CTCTGTAAAATAAATGCGCTGGGCCGGATCTTTTCTGAGTTCTCTTCTCCCCTACGAATTCTAGATCCCT CCTCTGTCCTCCCTGCGCCAGGGACCTTCGGGCGACCCTTCCCTGTACCCCCACCCCACCCTCTCTGGAC CCCGTTTCTGCCTCAGTACGGCGCGCTGAGCTCTGCCCCCTGCCCAGGCCCTGACCCCCTCAGGAGCCGC GGTTTCCTGGGGTAACAGTGGGAAACGTGTCGGCCGTCTCCGCTCAGGCGCTTGCTGTGTACAGAAAGGC TGATTCAGGCACACCGGCTCTCGTCGCCTTGGTGGCCCTCCCCAGCCCTCCTCCGCGCCTGCTCCGGGTG GCGCTCCGCTGGGCTCCTCGTGCGCCTGTCCGCGACCGCACCCACCTCATCCTGGCACCCCCATCGTGGC ATCACGTGTTCCCTCATCTGTCCTCATGGCTGGCGTGCCCCTCTGCGGTGAGACCTGCAGAACAGGAATT GGTGCCGGGTCAGCAGCCGGCGATGAAGCCGGACGAAGCCTGCAAACCCCACCCATACGCCAGCTTCACA TAGCTCCTATCCATTGCACAGCAGCGTGGGGAAGCACCGTTCTCTACCCTCCAAACAAAAGCATGAACCA GGTGCAGTGGCTCACGTCTGTAATCCCAGCATTTTGGAGGCCAAGGTGGATGGATGGATTCCTTGAGTCC AGGAGTTCAAGACCAGCCTGGGCAACATGGTGAACCCCCATCTCTACAAAAATTTAGCCAGTTTTCAGCT GCCCCCAGTTGCCTGGCCAGGCTGCCTCGACGGCCCTATTCACGGGCCCCAGCCTCCTCGCCGGGCTGGA AGGCGACAACCGCGAAAAGGAGGGTGACTCTCCTCGGCGGGGGCTTCGGGTGACATCACATCCTCCAAAT GCGAAATCAGGCTCCGGGCCGGCCGAAGGGCGCAACTTTCCCCCCTCGGCGCCCCACCGGCTCCCGCGCG CCTCCCCTCGCGCCCGAGCTTCGAGCCAAGCAGCGTCCTGGGGAGCGCGTCATGGCCTTACCAGTGACCG CCTTGCTCCTGCCGCTGGCCTTGCTGCTCCACGCCGCCAGGCCGAGCCAGTTCCGGGTGTCGCCGCTGGA TCGGACCTGGAACCTGGGCGAGACAGTGGAGCTGAAGTGCCAGGTGCTGCTGTCCAACCCGACGTCGGGC TGCTCGTGGCTCTTCCAGCCGCGCGGCGCCGCCGCCAGTCCCACCTTCCTCCTATACCTCTCCCAAAACA AGCCCAAGGCGGCCGAGGGGCTGGACACCCAGCGGTTCTCGGGCAAGAGGTTGGGGGACACCTTCGTCCT CACCCTGAGCGACTTCCGCCGAGAGAACGAGGGCTACTATTTCTGCTCGGCCCTGAGCAACTCCATCATG TACTTCAGCCACTTCGTGCCGGTCTTCCTGCCAGCGAAGCCCACCACGACGCCAGCGCCGCGACCACCAA CACCGGCGCCCACCATCGCGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGG CGCAGTGCACACGAGGGGGCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCTTGGCCGGGACTTGT GGGGTCCTTCTCCTGTCACTGGTTATCACCCTTTACTGCAACCACAGGAACCGAAGACGTGTTTGCAAAT GTCCCCGGCCTGTGGTCAAATCGGGAGACAAGCCCAGCCTTTCGGCGAGATACGTCTAACCCTGTGCAAC AGCCACTACATTACTTCAAACTGAGATCCTTCCTTTTGAGGGAGCAAGTCCTTCCCTTTCATTTTTTCCA GTCTTCCTCCCTGTGTATTCATTCTCATGATTATTATTTTAGTGGGGGCGGGGTGGGAAAGATTACTTTT TCTTTATGTGTTTGACGGGAAACAAAACTAGGTAAAATCTACAGTACACCACAAGGGTCACAATACTGTT GTGCGCACATCGCGGTAGGGCGTGGAAAGGGGCAGGCCAGAGCTACCCGCAGAGTTCTCAGAATCATGCT GAGAGAGCTGGAGGCACCCATGCCATCTCAACCTCTTCCCCGCCCGTTTTACAAAGGGGGAGGCTAAAGC CCAGAGACAGCTTGATCAAAGGCACACAGCAAGTCAGGGTTGGAGCAGTAGCTGGAGGGACCTTGTCTCC CAGCTCAGGGCTCTTTCCTCCACACCATTCAGGTCTTTCTTTCCGAGGCCCCTGTCTCAGGGTGAGGTGC TTGAGTCTCCAACGGCAAGGGAACAAGTACTTCTTGATACCTGGGATACTGTGCCCAGAGCCTCGAGGAG GTAATGAATTAAAGAAGAGAACTGCCTTTGGCAGAGTTCTATAATGTAAACAATATCAGACTTTTTTTTT TTATAATCAAGCCTAAAATTGTATAGACCTAAAATAAAATGAAGTGGTGAGCTTAACCCTGGAAAATGAA TCCCTCTATCTCTAAAGAAAATCTCTGTGAAACCCCTATGTGGAGGCGGAATTGCTCTCCCAGCCCTTGC ATTGCAGAGGGGCCCATGAAAGAGGACAGGCTACCCCTTTACAAATAGAATTTGAGCATCAGTGAGGTTA AACTAAGGCCCTCTTGAATCTCTGAATTTGAGATACAAACATGTTCCTGGGATCACTGATGACTTTTTAT ACTTTGTAAAGACAATTGTTGGAGAGCCCCTCACACAGCCCTGGCCTCTGCTCAACTAGCAGATACAGGG ATGAGGCAGACCTGACTCTCTTAAGGAGGCTGAGAGCCCAAACTGCTGTCCCAAACATGCACTTCCTTGC TTAAGGTATGGTACAAGCAATGCCTGCCCATTGGAGAGAAAAAACTTAAGTAGATAAGGAAATAAGAACC ACTCATAATTCTTCACCTTAGGAATAATCTCCTGTTAATATGGTGTACATTCTTCCTGATTATTTTCTAC ACATACATGTAAAATATGTCTTTCTTTTTTAAATAGGGTTGTACTATGCTGTTATGAGTGGCTTTAATGA ATAAACATTTGTAGCATCCTCTTTAATGGGTAAACAGCATCCGAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA AAAAAAAAAAAAAAAAAAAAAAAAAAA >NM_001382698.1 Homo sapiens CD8 subunit alpha (CD8A), transcript variant 5, mRNA GATTTGCGCAGAATGAGCGGCTGAGGATGGAAGGGCTGCAAGATCCACCGCCTTACTTAGCTGGGACCCG GCCCCACCTCCTCTACAGCAGACCCTGTCTCCACCGGTGCGGTTGGTGCTAGGTTCCCAAACACACTGCT GCCGTTTCTTGTCTGACATCGCGGCCCTGCTCCTGCCTGCCTTCAGCCTGGGCTAGCCCCCCGCCCTTCC CCCAGCTCCCTGCCCCTGCGCCCACCACACTCCTCCTCCGTCTCCTTTAGGCTGATTCAGGCACACCGGC TCTCGTCGCCTTGGTGGCCCTCCCCAGCCCTCCTCCGCGCCTGCTCCGGGTGGCGCTCCGCTGGGCTCCT CGTGCGCCTGTCCGCGACCGCACCCACCTCATCCTGGCACCCCCATCGTGGCATCACGTGTTCCCTCATC TGTCCTCATGGCTGGCGTGCCCCTCTGCGGTGAGACCTGCAGAACAGGAATTGGTGCCGGGTCAGCAGCC GGCGATGAAGCCGGACGAAGCCTGCAAACCCCACCCATACGCCAGCTTCACATAGCTCCTATCCATTGCA CAGCAGCGTGGGGAAGCACCGTTCTCTACCCTCCAAACAAAAGCATGAACCAGGTGCAGTGGCTCACGTC TGTAATCCCAGCATTTTGGAGGCCAAGGTGGATGGATGGATTCCTTGAGTCCAGGAGTTCAAGACCAGCC TGGGCAACATGGTGAACCCCCATCTCTACAAAAATTTAGCCAGTTTTCAGCTGCCCCCAGTTGCCTGGCC AGGCTGCCTCGACGGCCCTATTCACGGGCCCCAGCCTCCTCGCCGGGCTGGAAGGCGACAACCGCGAAAA GGAGGGTGACTCTCCTCGGCGGGGGCTTCGGGTGACATCACATCCTCCAAATGCGAAATCAGGCTCCGGG CCGGCCGAAGGGCGCAACTTTCCCCCCTCGGCGCCCCACCGGCTCCCGCGCGCCTCCCCTCGCGCCCGAG CTTCGAGCCAAGCAGCGTCCTGGGGAGCGCGTCATGGCCTTACCAGTGACCGCCTTGCTCCTGCCGCTGG CCTTGCTGCTCCACGCCGCCAGGCCGAGCCAGTTCCGGGTGTCGCCGCTGGATCGGACCTGGAACCTGGG CGAGACAGTGGAGCTGAAGTGCCAGGTGCTGCTGTCCAACCCGACGTCGGGCTGCTCGTGGCTCTTCCAG CCGCGCGGCGCCGCCGCCAGTCCCACCTTCCTCCTATACCTCTCCCAAAACAAGCCCAAGGCGGCCGAGG GGCTGGACACCCAGCGGTTCTCGGGCAAGAGGTTGGGGGACACCTTCGTCCTCACCCTGAGCGACTTCCG CCGAGAGAACGAGGGCTACTATTTCTGCTCGGCCCTGAGCAACTCCATCATGTACTTCAGCCACTTCGTG CCGGTCTTCCTGCCAGCGAAGCCCACCACGACGCCAGCGCCGCGACCACCAACACCGGCGCCCACCATCG CGTCGCAGCCCCTGTCCCTGCGCCCAGAGGCGTGCCGGCCAGCGGCGGGGGGCGCAGTGCACACGAGGGG GCTGGACTTCGCCTGTGATATCTACATCTGGGCGCCCTTGGCCGGGACTTGTGGGGTCCTTCTCCTGTCA CTGGTTATCACCCTTTACTGCAACCACAGGAACCGAAGACGTGTTTGCAAATGTCCCCGGCCTGTGGTCA AATCGGGAGACAAGCCCAGCCTTTCGGCGAGATACGTCTAACCCTGTGCAACAGCCACTACATTACTTCA AACTGAGATCCTTCCTTTTGAGGGAGCAAGTCCTTCCCTTTCATTTTTTCCAGTCTTCCTCCCTGTGTAT TCATTCTCATGATTATTATTTTAGTGGGGGCGGGGTGGGAAAGATTACTTTTTCTTTATGTGTTTGACGG GAAACAAAACTAGGTAAAATCTACAGTACACCACAAGGGTCACAATACTGTTGTGCGCACATCGCGGTAG GGCGTGGAAAGGGGCAGGCCAGAGCTACCCGCAGAGTTCTCAGAATCATGCTGAGAGAGCTGGAGGCACC CATGCCATCTCAACCTCTTCCCCGCCCGTTTTACAAAGGGGGAGGCTAAAGCCCAGAGACAGCTTGATCA AAGGCACACAGCAAGTCAGGGTTGGAGCAGTAGCTGGAGGGACCTTGTCTCCCAGCTCAGGGCTCTTTCC TCCACACCATTCAGGTCTTTCTTTCCGAGGCCCCTGTCTCAGGGTGAGGTGCTTGAGTCTCCAACGGCAA GGGAACAAGTACTTCTTGATACCTGGGATACTGTGCCCAGAGCCTCGAGGAGGTAATGAATTAAAGAAGA GAACTGCCTTTGGCAGAGTTCTATAATGTAAACAATATCAGACTTTTTTTTTTTATAATCAAGCCTAAAA TTGTATAGACCTAAAATAAAATGAAGTGGTGAGCTTAACCCTGGAAAATGAATCCCTCTATCTCTAAAGA AAATCTCTGTGAAACCCCTATGTGGAGGCGGAATTGCTCTCCCAGCCCTTGCATTGCAGAGGGGCCCATG AAAGAGGACAGGCTACCCCTTTACAAATAGAATTTGAGCATCAGTGAGGTTAAACTAAGGCCCTCTTGAA TCTCTGAATTTGAGATACAAACATGTTCCTGGGATCACTGATGACTTTTTATACTTTGTAAAGACAATTG TTGGAGAGCCCCTCACACAGCCCTGGCCTCTGCTCAACTAGCAGATACAGGGATGAGGCAGACCTGACTC TCTTAAGGAGGCTGAGAGCCCAAACTGCTGTCCCAAACATGCACTTCCTTGCTTAAGGTATGGTACAAGC AATGCCTGCCCATTGGAGAGAAAAAACTTAAGTAGATAAGGAAATAAGAACCACTCATAATTCTTCACCT TAGGAATAATCTCCTGTTAATATGGTGTACATTCTTCCTGATTATTTTCTACACATACATGTAAAATATG TCTTTCTTTTTTAAATAGGGTTGTACTATGCTGTTATGAGTGGCTTTAATGAATAAACATTTGTAGCATC CTCTTTAATGGGTAAACAGCA > CD8alpha (CD8A) ATGGCTCTGCCTGTGACAGCTCTGCTGCTGCCTCTGGCTCTGCTTCTGCATGCCGCTAGACCCAGCCAGTTCAGAGT GTCCCCTCTGGACAGAACCTGGAACCTGGGCGAGACAGTGGAACTGAAGTGCCAGGTGCTGCTGAGCAATCCTACCA GCGGCTGCAGCTGGCTGTTTCAGCCTAGAGGTGCTGCCGCCTCTCCTACCTTTCTGCTGTACCTGAGCCAGAACAAG CCCAAGGCCGCCGAAGGACTGGACACCCAGAGATTCAGCGGCAAGAGACTGGGCGACACCTTCGTGCTGACCCTGAG CGACTTCAGAAGAGAGAACGAGGGCTACTACTTCTGCAGCGCCCTGAGCAACAGCATCATGTACTTCAGCCACTTCG TGCCCGTGTTTCTGCCCGCCAAGCCTACAACAACCCCTGCTCCTAGACCTCCTACACCAGCTCCTACAATCGCCAGC CAGCCTCTGTCTCTGAGGCCAGAAGCTTGTAGACCTGCTGCTGGCGGAGCCGTGCATACAAGAGGACTGGATTTCGC CTGCGACATCTACATCTGGGCCCCTCTGGCTGGAACATGTGGCGTGCTGCTGCTGTCCCTGGTCATCACCCTGTACT GCAACCACCGGAACAGGCGGAGAGTGTGCAAGTGCCCTAGACCTGTGGTCAAGAGCGGCGACAAGCCTAGCCTGAGC GCCAGATATGTT By "CD8beta polypeptide" or "CD8β polypeptide" is meant a polypeptide having at least about 85% amino acid sequence identity to NCBI Accession Nos. XP_054200532.1, NP_757362.1, NP_742099.1, NP_742100.1, NP_004922.1, or NP_001171571.1, or a fragment thereof having co-receptor activity for ligand recognition by T cell receptors when dimerized with a CD8α. Exemplary CD8β amino acid sequences are provided below: >XP_054200532.1 T-cell surface glycoprotein CD8 beta chain isoform X1 [Homo sapiens] MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFL ALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPT TAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQKFN IVCLKISGFTTCCCFQILQMSREYGFGVLLQKDIGQ >NP_757362.1 T-cell surface glycoprotein CD8 beta chain isoform 2 precursor [Homo sapiens] MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFL ALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPT TAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQPQG EGISGTFVPQCLHGYYSNTTTSQKLLNPWILKT >NP_742099.1 T-cell surface glycoprotein CD8 beta chain isoform 3 precursor [Homo sapiens] MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFL ALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPT TAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQLRL HPLEKCSRMDY >NP_742100.1 T-cell surface glycoprotein CD8 beta chain isoform 4 precursor [Homo sapiens] MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFL ALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPT TAQPTKKSTLKKRVCRLPRPETQKGRRRRARLRFMKQPQGEGISGTFVPQCLHGYYSNTTTSQKLLNPWI LKT >NP_004922.1 T-cell surface glycoprotein CD8 beta chain isoform 5 precursor [Homo sapiens] MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFL ALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPT TAQPTKKSTLKKRVCRLPRPETQKGPLCSPITLGLLVAGVLVLLVSLGVAIHLCCRRRRARLRFMKQFYK >NP_001171571.1 T-cell surface glycoprotein CD8 beta chain isoform 6 precursor [Homo sapiens] MRPRLWLLLAAQLTVLHGNSVLQQTPAYIKVQTNKMVMLSCEAKISLSNMRIYWLRQRQAPSSDSHHEFL ALWDSAKGTIHGEEVEQEKIAVFRDASRFILNLTSVKPEDSGIYFCMIVGSPELTFGKGTQLSVVDFLPT TAQPTKKSTLKKRVCRLPRPETQKGLKGKVYQEPLSPNACMDTTAILQPHRSCLTHGS By "CD8beta polynucleotide" or "CD8β polynucleotide" is meant a nucleic acid molecule encoding a CD8β polypeptide. Exemplary CD8β polynucleotide sequences are provided below: >NM_004931.5 Homo sapiens CD8 subunit beta (CD8B), transcript variant 5, mRNA AGGTGTCCCGGGCGCGCCACGATGCGGCCGCGGCTGTGGCTCCTCTTGGCCGCGCAGCTGACAGTTCTCC ATGGCAACTCAGTCCTCCAGCAGACCCCTGCATACATAAAGGTGCAAACCAACAAGATGGTGATGCTGTC CTGCGAGGCTAAAATCTCCCTCAGTAACATGCGCATCTACTGGCTGAGACAGCGCCAGGCACCGAGCAGT GACAGTCACCACGAGTTCCTGGCCCTCTGGGATTCCGCAAAAGGGACTATCCACGGTGAAGAGGTGGAAC AGGAGAAGATAGCTGTGTTTCGGGATGCAAGCCGGTTCATTCTCAATCTCACAAGCGTGAAGCCGGAAGA CAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGAACTCAGCTGAGT GTGGTTGATTTCCTTCCCACCACTGCCCAGCCCACCAAGAAGTCCACCCTCAAGAAGAGAGTGTGCCGGT TACCCAGGCCAGAGACCCAGAAGGGCCCACTTTGTAGCCCCATCACCCTTGGCCTGCTGGTGGCTGGCGT CCTGGTTCTGCTGGTTTCCCTGGGAGTGGCCATCCACCTGTGCTGCCGGCGGAGGAGAGCCCGGCTTCGT TTCATGAAACAATTTTACAAATGAGCAGAGAATACGGTTTTGGTGTCCTGCTACAAAAAGACATCGGTCA GTAACGAGCACGATGTGGAAAAATGAGAGAAGGGACACATTCAACCCTGGAGAGTTCAATGGCTGCTGAA GCTGCCTGCTTTTCACTGCTGCAAGGCCTTTCTGTGTGTGATGTGCATGGGAGCAACTTGTTCGTGGGTC ATCGGGAATACTAGGGAGAAGGTTTCATTGCCCCCAGGGCACTTCACAGAGTGTGCTGGAGGACTGAGTA AGAAATGCTGCCCATGCCACCGCTTCCGGCTCCTGTGCTTTCCCTGAACTGGGACCTTTAGTGGTGGCCA TTTAGCCACCATCTTTGCAGGTTGCTTTGCCCTGGTAGGGCAGTAACATTGGGTCCTGGGTCTTTCATGG GGTGATGCTGGGCTGGCTCCCTCTTGGTCTTCCCAGGCTGGGGCTGACCTTCCTCGCAGAGAGGCCAGGT GCAGGTTGGGAATGAGGCTTGCTGAGAGGGGCTGTCCAGTTCCCAGAAGGCATATCAGTCTCTGAGGGCT TCCTTTGGGGCCGGGAACTTGCGGGTTTGAGGATAGGAGTTCACTTCATCTTCTCAGCTCCCATTTCTAC TCTTAAGTTTCTCAGCTCCCATTTCTACTCTCCCATGGCTTAATGCTTCTTTCATTTTCTGTTTGTTTTA TACAAATGTCTTAGTTGTACAAATAAAGTCCCAGGTTAAAGATAACAAACGGCTCCTGTGACATAAACGT GCGAAAGCCCATCTACAGCAAAGACATCAGTGCTCCGTGGAACAGAAACCAGAAGGAGAAAATTTGTACA TCCTCCTTTTGCACCTGAGATCCTCATTTGCCCGACGTTGTAGGTGTGGAGAGTCCTAGAGAGGCTAGGA AGCGCCCAGGGCACCCAGAGCCAGGCTGCAGGTGCCTCAGGCCCCTCTCCCAGCCCACTCCCAAGCTGAA CTAGCACGTGTTCATTTCTACCGCGGGTTGAACCGCAGGGATCCCTGGCTTCAAGTCAGGCACCAAACAG AAGGTAGGAGGCATGAGGGGTTCTGTCACATGTCTCTTCATTTTCTTATTGATTCTTAGCCTTGACAGTT GGAGAAGGAAAAAGCAAGGAGAAAGTGCTGAGCAGGAGTGGAGAGTGAAGAGCAGGACCTCGTGCCTGGG TTTGAAAAAGTGCCTGAGACCCATCTTAGCCGCCCCTACCTGAGCTTTAGCAGCCTAGGAGCTATTGCAC CATAAAACACTGCAACCTGAGGCTGCATTAACAGAAGCACCACGTCCAGGTCCAGGGAGAATCCAGCCTC ACCTGCTTTTCCTGGCCAGCTCAAAGAAGGACATTGACAAATCAGGTTATGTTCAGTTACCTGTGACAAC CACAGAATGTAAGAAATGTTACAAAAAAAACAGGAAAGGAAAGACGACTCTGGGGAAGGGGCAGTGTGAC CTTCTCCTGGCATCTGGGGTGCGGCCGCAGCAGAATGAGGTGTGGTGGGTGGAGTTAGAAAGGCATAGAT GCAGTGTTACCGGAAGGAGGGCCTTGAGTGTAAGTTGTCCAGGTCCTTGGCATTTTGAACAAAGAACTGA ACAAAACATACAAAGTAATAAAGGAATAAAAGCAGCAAAAGGAAGAATTTATTGAAGTGAGAAAGCACTC CACATGGTAGGAGTGGACCCTAAGCAGATAGCCCATGGGCCCAATTGCAAAGTTTTCTGGGTTTTAAGTA CCCCTTTTGAGGTACCTGTTGGCTACCCCTTATCTGGGTGAAGGATTTGGTCCATGGCTAATGAAAGGCT GAGGTGAATTGACGCCCTATGCGGATGAAGGGATGGCCCGTGCTTGGTCTGTGGTCAATCCAGGGCCGTC TCCCTTTCCATCTGAGATGCAGTGGAAGGGGGAGGGTTGTAGGGAGAGTAGCCTTTGATCCTTGGTTACT CAGTGTGGGGAGATGGGGTTTTTCCTTTTGGTGTATGTTAATTGGCCTTAGATGCCCTGCCCCCAGACCC AGGTGTTTTCCGTTTGCTCCAGCTTTGAGAAGTCAGCACAAATTGGCCTCAGATTCCCTGCCCCCAGACG TAGGTGTTTCTCCTTCATTCAGCACGAATTGGCCTTAGATGCCCTGCCCCCAGACCCAGGTGTTTTCCAT TTGATCCAGCTTTGAGAAGTCAGCACAAATTGGCCTCAGATTCCCTGCCCCCGGACATAGATGTTTCTCC TTGATTCAGCACGAATTGGCCTTAGATTCCCTGCCCCCAGACCCTAGACTCCTGCCTCAGCAAGAGGTGT TCAAAAGAAACAAAAGCTCTGCCCATCAGCTCTGAGGACAAGGGACAGGCTGCCTTCCAAGGCTGAGGGG AGGGGTGAAAGAATTGGGGTCAGCTGGACCAGACTCCTCTAGGGTTCGTGTTTCAGGTGGGCCCCTCACC CGGCCCATCACAAACAAATAAGAGATTAAGGCCTGCAGTGCACATGGTCTGCCCTCCTTGAAGGCTCACA CCCAGTGCACAGCGGAAGTAAGAACAGGCCACAAGGCCTCTTGTCCCACTGCAGGCTTTGAAATTTGACC GTCTCCCTGCTGCTGTCTTTGCAATTGCATGTACTTGTTCACAAGTTCTCATGGGGTTGGGCTGGGGGCA GGGGTGGTTTGCGCTCCTCTGTCAGTTTTCTGTGCAGCAGGCACCTGCCGAGGCGGGCTCAGCTCCGGCT GCCCAGGGAGCTGGAGCAGGCTGGGCTGCCAATGGTGGGGGCTGCGGTGAGAAGGTCTGCACCCAGCACC TGACCTTTGTTTGAAGAAGGAGCTGAGCTGCTACTACACTCTATAGGGCCATTATGATGAAATATGCCCC CCAAACTCCATCCAGCTATCTTTTGACTAGCAATTCCACTTGTTGGCATTTATCTGAAAGAAATACATCA AAAAGTGGCATGCACAAAGAAATACGCATCAGATTGTTCCTTCTAGTGTTGCTTACTAGCTAAAAATGGG AAATAATCCAAATGTCCATCAAAAGGGACTGGTCAGATAAATTCAGACACAGTCTAATAAGGGGGTTTAG GCGGCTGCTAAGGAATGAGCTAGATCCATATATGCTGATATCAAATGATGGTTATGACAAATGCATATAT TTTTAAAACATCTGTATAGATTATTCTTAATACAATATATGGCACAATATGTAGTCACTGTTAAAATTCA AGCACAAAAGAAAACAAGCAAAACAAATATATGTTGTTAGAAGTTAGGATACAGTTACCCTTGGTCCAGT GGTGGTCATTAGGAGGGAGCATGAGGTTTGAAGGTGAGCATTTCTGCTTCTCAATCTGGGAATCACTTAT ATGAGTGTGTTTCATTAGTAAAAGTCATCAAGCTGTACACTCAGATATGTTGACTTTAGAGCTATGGATA TAGATGTAAATTATACTTCAAGAAAGAGACTTTTTAAAATCCAAGTACAGAACATTGTAGAAATGTGTAA AATTGGTATTTGGAAGTTTCTTCAGCAAGCACATGGGATTACAGCTCACGCCTGTAATCCCAGTACTTTG GGAGGCCCACACAGAATGATCACTTGAGCTCAGGAGTTTGAGAGCAGCCTAGGCAACATAGCAAGACCTC GACTCTACAAAAAATTTTTAAATTTTTTTCTGGGCATGGTGGTGCTTGCCTGTAGTCCCAGCTATTAGGG AGGATGAGGTGGGAGGATCTCCTGACCCCAGGAGTTTCAGACTGCAGTGAGCTGTGATCACGCCACTGCA CTCCAGCCTGGGCAACACAGACAGACCTTGTCTCAAAAATAAATTTTTTCTAAAAAGTTTCTTGTTTTTT TTTCTTCCCATATTTTTTAAAACATAAAATTGAAATCTTGAGAATATAATACATAAAATAGAGAATATAG AAAATTACATCTTCTAATATTGTTCTGCAGATTTGATCTTTTTTCTCTAATAATAAATCAAGGCCTCCGG GTATATTTGTTTGTATATGTACAGGAAAAGGTCTGTAAGGATTTACTTTCAGCTGTTAATTGCAGTTACT CTGCGGAATTTCCACTTCTGCTTTGTACAGTTCCTTGTGTGAATTTTTACATCATGTATTACTTTTGTAG TTGGGGAAAAAGCAATTAAAAGTTTGGAAAAAAA >NM_172101.5 Homo sapiens CD8 subunit beta (CD8B), transcript variant 3, mRNA AGGTGTCCCGGGCGCGCCACGATGCGGCCGCGGCTGTGGCTCCTCTTGGCCGCGCAGCTGACAGTTCTCC ATGGCAACTCAGTCCTCCAGCAGACCCCTGCATACATAAAGGTGCAAACCAACAAGATGGTGATGCTGTC CTGCGAGGCTAAAATCTCCCTCAGTAACATGCGCATCTACTGGCTGAGACAGCGCCAGGCACCGAGCAGT GACAGTCACCACGAGTTCCTGGCCCTCTGGGATTCCGCAAAAGGGACTATCCACGGTGAAGAGGTGGAAC AGGAGAAGATAGCTGTGTTTCGGGATGCAAGCCGGTTCATTCTCAATCTCACAAGCGTGAAGCCGGAAGA CAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGAACTCAGCTGAGT GTGGTTGATTTCCTTCCCACCACTGCCCAGCCCACCAAGAAGTCCACCCTCAAGAAGAGAGTGTGCCGGT TACCCAGGCCAGAGACCCAGAAGGGCCCACTTTGTAGCCCCATCACCCTTGGCCTGCTGGTGGCTGGCGT CCTGGTTCTGCTGGTTTCCCTGGGAGTGGCCATCCACCTGTGCTGCCGGCGGAGGAGAGCCCGGCTTCGT TTCATGAAACAACTAAGATTACATCCACTGGAGAAATGTTCCAGAATGGACTACTGAATATACAGGCCTC AAGGGGAAGGTATATCAGGAACCTTTGTCCCCCAATGCCTGCATGGATACTACAGCAATACTACAACCTC ACAGAAGCTGCTTAACCCATGGATCCTGAAAACATAGGCAAGAAGCACAGGTCCTGATGAGTGGATCTTT ACTACTTTTACCAGATTCCTCCCTCGCTCAGAGGGATCCTCCCACACACCCAGCAGAGACTTCTCTGCCA CCATCAACCCCCCAAGTCATAGGGGGCTCAAGTTCTGCCCTGGTGAGCTGTGGCCCCCATCCTTGTGAAC CCCAAAGTGTCCCCCTTGTGGAACCAAATGTATCCATCTTGAATAAATTTGCCCAAAATCCTAAA >NM_172102.5 Homo sapiens CD8 subunit beta (CD8B), transcript variant 4, mRNA AGGTGTCCCGGGCGCGCCACGATGCGGCCGCGGCTGTGGCTCCTCTTGGCCGCGCAGCTGACAGTTCTCC ATGGCAACTCAGTCCTCCAGCAGACCCCTGCATACATAAAGGTGCAAACCAACAAGATGGTGATGCTGTC CTGCGAGGCTAAAATCTCCCTCAGTAACATGCGCATCTACTGGCTGAGACAGCGCCAGGCACCGAGCAGT GACAGTCACCACGAGTTCCTGGCCCTCTGGGATTCCGCAAAAGGGACTATCCACGGTGAAGAGGTGGAAC AGGAGAAGATAGCTGTGTTTCGGGATGCAAGCCGGTTCATTCTCAATCTCACAAGCGTGAAGCCGGAAGA CAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGAACTCAGCTGAGT GTGGTTGATTTCCTTCCCACCACTGCCCAGCCCACCAAGAAGTCCACCCTCAAGAAGAGAGTGTGCCGGT TACCCAGGCCAGAGACCCAGAAGGGCCGGCGGAGGAGAGCCCGGCTTCGTTTCATGAAACAGCCTCAAGG GGAAGGTATATCAGGAACCTTTGTCCCCCAATGCCTGCATGGATACTACAGCAATACTACAACCTCACAG AAGCTGCTTAACCCATGGATCCTGAAAACATAGGCAAGAAGCACAGGTCCTGATGAGTGGATCTTTACTA CTTTTACCAGATTCCTCCCTCGCTCAGAGGGATCCTCCCACACACCCAGCAGAGACTTCTCTGCCACCAT CAACCCCCCAAGTCATAGGGGGCTCAAGTTCTGCCCTGGTGAGCTGTGGCCCCCATCCTTGTGAACCCCA AAGTGTCCCCCTTGTGGAACCAAATGTATCCATCTTGAATAAATTTGCCCAAAATCCTAAA >NM_172213.5 Homo sapiens CD8 subunit beta (CD8B), transcript variant 2, mRNA AGGTGTCCCGGGCGCGCCACGATGCGGCCGCGGCTGTGGCTCCTCTTGGCCGCGCAGCTGACAGTTCTCC ATGGCAACTCAGTCCTCCAGCAGACCCCTGCATACATAAAGGTGCAAACCAACAAGATGGTGATGCTGTC CTGCGAGGCTAAAATCTCCCTCAGTAACATGCGCATCTACTGGCTGAGACAGCGCCAGGCACCGAGCAGT GACAGTCACCACGAGTTCCTGGCCCTCTGGGATTCCGCAAAAGGGACTATCCACGGTGAAGAGGTGGAAC AGGAGAAGATAGCTGTGTTTCGGGATGCAAGCCGGTTCATTCTCAATCTCACAAGCGTGAAGCCGGAAGA CAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGAACTCAGCTGAGT GTGGTTGATTTCCTTCCCACCACTGCCCAGCCCACCAAGAAGTCCACCCTCAAGAAGAGAGTGTGCCGGT TACCCAGGCCAGAGACCCAGAAGGGCCCACTTTGTAGCCCCATCACCCTTGGCCTGCTGGTGGCTGGCGT CCTGGTTCTGCTGGTTTCCCTGGGAGTGGCCATCCACCTGTGCTGCCGGCGGAGGAGAGCCCGGCTTCGT TTCATGAAACAGCCTCAAGGGGAAGGTATATCAGGAACCTTTGTCCCCCAATGCCTGCATGGATACTACA GCAATACTACAACCTCACAGAAGCTGCTTAACCCATGGATCCTGAAAACATAGGCAAGAAGCACAGGTCC TGATGAGTGGATCTTTACTACTTTTACCAGATTCCTCCCTCGCTCAGAGGGATCCTCCCACACACCCAGC AGAGACTTCTCTGCCACCATCAACCCCCCAAGTCATAGGGGGCTCAAGTTCTGCCCTGGTGAGCTGTGGC CCCCATCCTTGTGAACCCCAAAGTGTCCCCCTTGTGGAACCAAATGTATCCATCTTGAATAAATTTGCCC AAAATCCTAAA >NM_001178100.2 Homo sapiens CD8 subunit beta (CD8B), transcript variant 6, mRNA AGGTGTCCCGGGCGCGCCACGATGCGGCCGCGGCTGTGGCTCCTCTTGGCCGCGCAGCTGACAGTTCTCC ATGGCAACTCAGTCCTCCAGCAGACCCCTGCATACATAAAGGTGCAAACCAACAAGATGGTGATGCTGTC CTGCGAGGCTAAAATCTCCCTCAGTAACATGCGCATCTACTGGCTGAGACAGCGCCAGGCACCGAGCAGT GACAGTCACCACGAGTTCCTGGCCCTCTGGGATTCCGCAAAAGGGACTATCCACGGTGAAGAGGTGGAAC AGGAGAAGATAGCTGTGTTTCGGGATGCAAGCCGGTTCATTCTCAATCTCACAAGCGTGAAGCCGGAAGA CAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGAACTCAGCTGAGT GTGGTTGATTTCCTTCCCACCACTGCCCAGCCCACCAAGAAGTCCACCCTCAAGAAGAGAGTGTGCCGGT TACCCAGGCCAGAGACCCAGAAGGGCCTCAAGGGGAAGGTATATCAGGAACCTTTGTCCCCCAATGCCTG CATGGATACTACAGCAATACTACAACCTCACAGAAGCTGCTTAACCCATGGATCCTGAAAACATAGGCAA GAAGCACAGGTCCTGATGAGTGGATCTTTACTACTTTTACCAGATTCCTCCCTCGCTCAGAGGGATCCTC CCACACACCCAGCAGAGACTTCTCTGCCACCATCAACCCCCCAAGTCATAGGGGGCTCAAGTTCTGCCCT GGTGAGCTGTGGCCCCCATCCTTGTGAACCCCAAAGTGTCCCCCTTGTGGAACCAAATGTATCCATCTTG AATAAATTTGCCCAAAATCCTAAA >XM_011533164.3 PREDICTED: Homo sapiens CD8 subunit beta (CD8B), transcript variant X1, mRNA AGGTGTCCCGGGCGCGCCACGATGCGGCCGCGGCTGTGGCTCCTCTTGGCCGCGCAGCTGACAGTTCTCC ATGGCAACTCAGTCCTCCAGCAGACCCCTGCATACATAAAGGTGCAAACCAACAAGATGGTGATGCTGTC CTGCGAGGCTAAAATCTCCCTCAGTAACATGCGCATCTACTGGCTGAGACAGCGCCAGGCACCGAGCAGT GACAGTCACCACGAGTTCCTGGCCCTCTGGGATTCCGCAAAAGGGACTATCCACGGTGAAGAGGTGGAAC AGGAGAAGATAGCTGTGTTTCGGGATGCAAGCCGGTTCATTCTCAATCTCACAAGCGTGAAGCCGGAAGA CAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGAACTCAGCTGAGT GTGGTTGATTTCCTTCCCACCACTGCCCAGCCCACCAAGAAGTCCACCCTCAAGAAGAGAGTGTGCCGGT TACCCAGGCCAGAGACCCAGAAGGGCCCACTTTGTAGCCCCATCACCCTTGGCCTGCTGGTGGCTGGCGT CCTGGTTCTGCTGGTTTCCCTGGGAGTGGCCATCCACCTGTGCTGCCGGCGGAGGAGAGCCCGGCTTCGT TTCATGAAACAGAAATTCAATATCGTTTGCCTGAAAATAAGTGGTTTCACAACTTGCTGTTGTTTTCAGA TTTTACAAATGAGCAGAGAATACGGTTTTGGTGTCCTGCTACAAAAAGACATCGGTCAGTAACGAGCACG ATGTGGAAAAATGAGAGAAGGGACACATTCAACCCTGGAGAGTTCAATGGCTGCTGAAGCTGCCTGCTTT TCACTGCTGCAAGGCCTTTCTGTGTGTGATGTGCATGGGAGCAACTTGTTCGTGGGTCATCGGGAATACT AGGGAGAAGGTTTCATTGCCCCCAGGGCACTTCACAGAGTGTGCTGGAGGACTGAGTAAGAAATGCTGCC CATGCCACCGCTTCCGGCTCCTGTGCTTTCCCTGAACTGGGACCTTTAGTGGTGGCCATTTAGCCACCAT CTTTGCAGGTTGCTTTGCCCTGGTAGGGCAGTAACATTGGGTCCTGGGTCTTTCATGGGGTGATGCTGGG CTGGCTCCCTCTTGGTCTTCCCAGGCTGGGGCTGACCTTCCTCGCAGAGAGGCCAGGTGCAGGTTGGGAA TGAGGCTTGCTGAGAGGGGCTGTCCAGTTCCCAGAAGGCATATCAGTCTCTGAGGGCTTCCTTTGGGGCC GGGAACTTGCGGGTTTGAGGATAGGAGTTCACTTCATCTTCTCAGCTCCCATTTCTACTCTTAAGTTTCT CAGCTCCCATTTCTACTCTCCCATGGCTTAATGCTTCTTTCATTTTCTGTTTGTTTTATACAAATGTCTT AGTTGTACAAATAAAGTCCCAGGTTAAAGATAACAAACGGCTCCTGTGACATAAACGTGCGAAAGCCCAT CTACAGCAAAGACATCAGTGCTCCGTGGAACAGAAACCAGAAGGAGAAAATTTGTACATCCTCCTTTTGC ACCTGAGATCCTCATTTGCCCGACGTTGTAGGTGTGGAGAGTCCTAGAGAGGCTAGGAAGCGCCCAGGGC ACCCAGAGCCAGGCTGCAGGTGCCTCAGGCCCCTCTCCCAGCCCACTCCCAAGCTGAACTAGCACGTGTT CATTTCTACCGCGGGTTGAACCGCAGGGATCCCTGGCTTCAAGTCAGGCACCAAACAGAAGGTAGGAGGC ATGAGGGGTTCTGTCACATGTCTCTTCATTTTCTTATTGATTCTTAGCCTTGACAGTTGGAGAAGGAAAA AGCAAGGAGAAAGTGCTGAGCAGGAGTGGAGAGTGAAGAGCAGGACCTCGTGCCTGGGTTTGAAAAAGTG CCTGAGACCCATCTTAGCCGCCCCTACCTGAGCTTTAGCAGCCTAGGAGCTATTGCACCATAAAACACTG CAACCTGAGGCTGCATTAACAGAAGCACCACGTCCAGGTCCAGGGAGAATCCAGCCTCACCTGCTTTTCC TGGCCAGCTCAAAGAAGGACATTGACAAATCAGGTTATGTTCAGTTACCTGTGACAACCACAGAATGTAA GAAATGTTACAAAAAAAACAGGAAAGGAAAGACGACTCTGGGGAAGGGGCAGTGTGACCTTCTCCTGGCA TCTGGGGTGCGGCCGCAGCAGAATGAGGTGTGGTGGGTGGAGTTAGAAAGGCATAGATGCAGTGTTACCG GAAGGAGGGCCTTGAGTGTAAGTTGTCCAGGTCCTTGGCATTTTGAACAAAGAACTGAACAAAACATACA AAGTAATAAAGGAATAAAAGCAGCAAAA >XM_054344557.1 PREDICTED: Homo sapiens CD8 subunit beta (CD8B), transcript variant X1, mRNA AGGTGTCCCGGGCGCGCCACGATGCGGCCGCGGCTGTGGCTCCTCTTGGCCGCGCAGCTGACAGTTCTCC ATGGCAACTCAGTCCTCCAGCAGACCCCTGCATACATAAAGGTGCAAACCAACAAGATGGTGATGCTGTC CTGCGAGGCTAAAATCTCCCTCAGTAACATGCGCATCTACTGGCTGAGACAGCGCCAGGCACCGAGCAGT GACAGTCACCACGAGTTCCTGGCCCTCTGGGATTCCGCAAAAGGGACTATCCACGGTGAAGAGGTGGAAC AGGAGAAGATAGCTGTGTTTCGGGATGCAAGCCGGTTCATTCTCAATCTCACAAGCGTGAAGCCGGAAGA CAGTGGCATCTACTTCTGCATGATCGTCGGGAGCCCCGAGCTGACCTTCGGGAAGGGAACTCAGCTGAGT GTGGTTGATTTCCTTCCCACCACTGCCCAGCCCACCAAGAAGTCCACCCTCAAGAAGAGAGTGTGCCGGT TACCCAGGCCAGAGACCCAGAAGGGCCCACTTTGTAGCCCCATCACCCTTGGCCTGCTGGTGGCTGGCGT CCTGGTTCTGCTGGTTTCCCTGGGAGTGGCCATCCACCTGTGCTGCCGGCGGAGGAGAGCCCGGCTTCGT TTCATGAAACAGAAATTCAATATCGTTTGCCTGAAAATAAGTGGTTTCACAACTTGCTGTTGTTTTCAGA TTTTACAAATGAGCAGAGAATACGGTTTTGGTGTCCTGCTACAAAAAGACATCGGTCAGTAACGAGCACG ATGTGGAAAAATGAGAGAAGGGACACATTCAACCCTGGAGAGTTCAATGGCTGCTGAAGCTGCCTGCTTT TCACTGCTGCAAGGCCTTTCTGTGTGTGATGTGCATGGGAGCAACTTGTTCGTGGGTCATCGGGAATACT AGGGAGAAGGTTTCATTGCCCCCAGGGCACTTCACAGAGTGTGCTGGAGGACTGAGTAAGAAATGCTGCC CATGCCACCGCTTCCGGCTCCTGTGCTTTCCCTGAACTGGGACCTTTAGTGGTGGCCATTTAGCCACCAT CTTTGCAGGTTGCTTTGCCCTGGTAGGGCAGTAACATTGGGTCCTGGGTCTTTCATGGGGTGATGCTGGG CTGGCTCCCTCTTGGTCTTCCCAGGCTGGGGCTGACCTTCCTCGCAGAGAGGCCAGGTGCAGGTTGGGAA TGAGGCTTGCTGAGAGGGGCTGTCCAGTTCCCAGAAGGCATATCAGTCTCTGAGGGCTTCCTTTGGGGCC GGGAACTTGCGGGTTTGAGGATAGGAGTTCACTTCATCTTCTCAGCTCCCATTTCTACTCTTAAGTTTCT CAGCTCCCATTTCTACTCTCCCATGGCTTAATGCTTCTTTCATTTTCTGTTTGTTTTATACAAATGTCTT AGTTGTACAAATAAAGTCCCAGGTTAAAGATAA >CD8beta (CD8B) ATGAGGCCTAGACTGTGGCTGCTTCTGGCTGCCCAGCTGACAGTGCTGCACGGCAATTCTGTCCTGCAGCAGACCCC TGCCTACATCAAGGTGCAGACCAACAAGATGGTCATGCTGAGCTGCGAGGCCAAGATCAGCCTGTCCAACATGCGGA TCTACTGGCTGCGGCAGAGACAGGCCCCTAGCTCTGATAGCCACCACGAGTTTCTGGCCCTGTGGGATTCTGCCAAG GGCACCATTCACGGCGAGGAAGTGGAACAAGAGAAGATCGCCGTGTTCCGGGACGCCAGCAGATTCATCCTGAACCT GACCAGCGTGAAGCCCGAGGACAGCGGCATCTATTTCTGCATGATCGTGGGCAGCCCCGAGCTGACATTTGGCAAGG GAACACAGCTGAGCGTGGTGGACTTCCTGCCTACTACAGCCCAGCCTACCAAGAAGTCTACCCTGAAGAAACGCGTG TGCAGACTGCCCAGGCCTGAGACACAAAAGGGCCCTCTGTGCAGCCCTATCACACTGGGATTGCTGGTGGCTGGCGT TCTGGTCCTGCTGGTGTCTCTGGGAGTTGCCATCCACCTGTGCTGTAGAAGAAGGCGGGCCAGACTGCGGTTCATGA AGCAGTTCTACAAA By "chimeric antigen receptor (CAR)" is meant an engineered receptor comprising an extracellular domain (e.g., scFv) that specifically binds to an antigen and one or more intracellular signaling domains (e.g., T cell signaling domain) that confers specificity for an antigen onto an immune effector cell. By "cognate peptide" is meant a peptide that is specifically recognized by a binding protein. A cognate peptide of a TCR is recognized by the TCR when presented or otherwise associated with a major histocompatibility (MHC) protein. As used herein, the term "complementarity determining region" (CDR) refers to a hypervariable region found within an immunoglobulin superfamily member (e.g., TCR) variable region, which confers antigen specificity or binding affinity. CDRs are separated from one another in primary amino acid sequence by framework regions. These particular regions have been described by Kabat et al., J. Biol. Chem.252:6609-6616, 1977 and Kabat, et al., Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No.91-3242, 1991; by Chothia et al., (J. Mol. Biol.196:901-917, 1987), and by MacCallum et al., (J. Mol. Biol.262:732-745, 1996) where the definitions include overlapping or subsets of amino acid residues when compared against each other. In certain embodiments, the term "CDR" is a CDR as defined by Kabat based on sequence comparisons. The more highly conserved portions of variable domains are called the framework regions (FRs). As used herein, numbering of immunoglobulin amino acid residues is done according to the immunoglobulin amino acid residue numbering system of Kabat et al., unless otherwise indicated. In general, there are three CDRs in each TCR α-chain variable region (αCDR1, αCDR2, αCDR3) and three CDRs in each TCR β-chain variable region (βCDR1, βCDR2, βCDR3). In TCRs, CDR3 is involved in recognizing processed antigen presented by the MHC, whereas CDR1 and CDR2 interact mainly or exclusively with the MHC. CDR1 and CDR2 are encoded within the variable gene segment of a TCR variable region-coding sequence, whereas CDR3 is encoded by the region spanning the variable and joining segments for Vα, or the region spanning variable, diversity, and joining segments for Vβ. Thus, if the identity of the variable gene segment of a Vα or Vβ is described, the sequences of their corresponding CDR1 and CDR2 can be deduced, e.g., according to a numbering scheme as described herein. Compared with CDR1 and CDR2, CDR3 can be significantly more diverse due to the addition and loss of nucleotides during the recombination process. TCR variable domain sequences can be aligned to a numbering scheme (e.g., Kabat, Chothia, EU, IMGT, Enhanced Chothia, and Aho), allowing equivalent residue positions to be annotated and for different molecules to be compared using, for example, ANARCI software tool (2016, Bioinformatics 15:298-300). A numbering scheme provides a standardized delineation of framework regions and CDRs in the TCR variable domains. In certain embodiments, a CDR of the present disclosure is identified according to the IMGT numbering scheme or method (Lefranc et al., Dev. Comp. Immunol.27:55, 2003; imgt.org / IMGTindex / V-QUEST.php). In some embodiments, a CDR of the present disclosure is identified according to the Kabat numbering scheme or method. In some embodiments, a CDR of the present disclosure is identified according to the Chothia numbering scheme or method. In some embodiments, a CDR of the present disclosure is identified according to the EU numbering scheme or method. In some embodiments, a CDR of the present disclosure is identified according to the enhanced Chothia numbering scheme or method. In some embodiments, a CDR of the present disclosure is identified according to the Aho numbering scheme or method. By "construct" is meant an a engineered polynucleotide that is designed to be introduced to a target cell where it alters gene expression. In an embodiment, the construct is a vector (e.g., plasmid) configured for expression in a target cell. In an embodiment, the construct may be a a viral vector. Physical or chemical methods (e.g., electroporation) may be used to facilitate transfer into the target cell. In an embodiment, the construct is integrated into the genome of a target cell. By "decreases" is meant a reduction by at least about 5% relative to a reference level. A decrease may be by 5%, 10%, 15%, 20%, 25% or 50%, or even by as much as 75%, 85%, 95% or more and any intervening percentages. "Detect" refers to identifying the presence, absence or amount of the analyte to be detected. By "disease" is meant any condition or disorder that damages or interferes with the normal function of a cell, tissue, or organ. In one embodiment, the disease is a cancer associated with an alteration in a p53 polypeptide or in a polynucleotide encoding said polypeptide. In embodiments, a cancer associated with a p53 mutation is a colorectal cancer, esophageal cancer, head and neck cancer, larynx cancer, lung cancer (e.g., small cell lung cancer, squamous cell lung cancer), breast cancer (e.g., triple-negative breast cancer), endometrial cancer, skin cancer (e.g., melanoma) and ovarian cancer (e.g., high-grade serous ovarian cancer). In an embodiment, the disease is in a subject expressing human leukocyte antigen (HLA) serotype HLA-A*02. By "endogenous" is meant originating from within a tissue or cell of an organism. By a "naïve" tissue or cell is meant a tissue or cell that has not been engineered to express a heterologous polynucleotide or polypeptide. The term "expression" or "expressed" as used herein in reference to a gene means the process of producing a transcriptional and / or translational product of that gene. The level of expression of a DNA molecule in a cell may be determined on the basis of either the amount of corresponding mRNA that is present within the cell or the amount of protein encoded by that DNA produced by the cell (Sambrook et al., 1989 Molecular Cloning: A Laboratory Manual, 18.1-18.88). By "effective amount" is meant the amount of an agent required to ameliorate one or more symptom of a disease relative to an untreated patient. The effective amount of active agent used to practice the present invention for therapeutic treatment of a disease varies depending upon the manner of administration, the age, body weight, and general health of the subject. Ultimately, the attending physician or veterinarian will decide the appropriate amount and dosage regimen. Such an amount is referred to as an "effective" amount. By "epitope" is meant the portion of an antigen to which a binding proteinspecifically binds. In some embodiments, the epitope comprises a p53 R175H mutant. By "fragment" is meant a portion of a polypeptide or nucleic acid molecule. This portion contains at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 10, 20, 30, 40, 50, 60, 70, 80, 90, or 100, 200, 300, 400, 500, 600, 700, 800, 900, or 1000 nucleotides or amino acids. A "functional fragment" as used herein is a fragment of a polypeptide or polynucleotide molecule that retains at least one biological activity of the polypeptide or polynucleotide molecule from which it is derived. By "increase" is meant to alter positively relative to a reference. An increase may be by 1%, 5%, 10%, 25%, 30%, 50%, 75%, 100%, or more, or by 1.5-fold, 2-fold, 3-fold, 4-fold, 5- fold, 6-fold, 7-fold, 8-fold, 9-fold, 10-fold, 25-fold, 50-fold, 75-fold, 100-fold, or more. As used herein, a(n) "heterologous" or "exogenous" nucleic acid molecule, construct, or sequence refers to a nucleic acid molecule, or portion of a nucleic acid molecule, that is not native to a host cell but can be homologous to a nucleic acid molecule or portion thereof from the host cell. The source of the heterologous or exogenous nucleic acid molecule, construct, or sequence can be from a different genus or species. In certain embodiments, a heterologous or exogenous nucleic acid molecule (i.e., not endogenous or native) is added to a host cell or host genome by, for example, conjugation, transformation, transfection, transduction, electroporation, or the like, wherein the added molecule can integrate into the host genome or exist as extra- chromosomal genetic material (e.g., as a plasmid or other form of self-replicating vector), and can be present in multiple copies. In addition, "heterologous" refers to a non-native enzyme, protein, polypeptide, or other activity encoded by an exogenous nucleic acid molecule introduced into the host cell, even if the host cell encodes a homologous protein or activity. Moreover, a cell comprising a "modification" or a "heterologous" polynucleotide or binding protein includes progeny of that cell, regardless of whether the progeny were themselves transduced, transfected, or otherwise manipulated or changed. A "host cell" or "cell" is any prokaryotic or eukaryotic cell that contains either a cloning vector or an expression vector. This term also includes those prokaryotic or eukaryotic cells that have been genetically engineered to contain the cloned gene(s) in the chromosome or genome of the host cell. In some embodiments, the host cell is an immune cell (e.g., T cell, macrophage, natural killer cell). In some embodiments, the host cell is an induced pluripotent stem (iPS) cell, or a derivative thereof. iPS host cells of the present disclosure may be modified before, during, and / or after differentiation. In some embodiments, the host cell comprises a vector comprising a polynucleotide encoding a heterologous TCR of the present disclosure. In some embodiments, the host cell expresses a heterologous TCR of the present disclosure. "Hybridization" means hydrogen bonding, which may be Watson-Crick, Hoogsteen or reversed Hoogsteen hydrogen bonding, between complementary nucleobases. For example, adenine and thymine are complementary nucleobases that pair through the formation of hydrogen bonds. As used herein, an "immune cell" generally refers to any cell of the immune system. In embodiments, an immune cell originates from a hematopoietic stem cell in the bone marrow, which gives rise to two major lineages, a myeloid progenitor cell (which gives rise to myeloid cells such as monocytes, macrophages, dendritic cells, megakaryocytes and granulocytes) and a lymphoid progenitor cell (which give rise to lymphoid cells such as T cells, B cells and natural killer (NK) cells). Example immune system cells include a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a γδ T cell, a regulatory T cell, a natural killer cell, a natural killer T cell, and a dendritic cell. Macrophages and dendritic cells can be referred to as "antigen presenting cells" or "APCs," which are specialized cells that can activate T cells when a major histocompatibility complex (MHC) receptor on the surface of the APC complexed with a peptide interacts with a TCR on the surface of a T cell. As referred to herein, a "transformed," "transduced," or "transfected" cell is a cell into which a nucleic acid molecule or polynucleotide sequence has been introduced by artificial means (e.g., using molecular biology techniques). As used herein, the term "transfection" encompasses all techniques by which a nucleic acid molecule or polynucleotide may be introduced into such a cell, including transformation with plasmid vectors and introduction of naked nucleic acid (DNA or RNA) by electroporation, lipofection, and particle gun acceleration. As used herein, the term "transduction" encompasses viral and / or viral vector-mediated techniques by which a nucleic acid molecule or polynucleotide may be introduced into such a cell. As used herein, "transformation" refers to the introduction of nucleic acids into a bacterial cell. The terms "isolated," "purified," or "biologically pure" refer to material that is free to varying degrees from components which normally accompany it as found in its native state. "Isolate" denotes a degree of separation from original source or surroundings. "Purify" denotes a degree of separation that is higher than isolation. A "purified" or "biologically pure" protein is sufficiently free of other materials such that any impurities do not materially affect the biological properties of the protein or cause other adverse consequences. That is, a nucleic acid or peptide of this invention is purified if it is substantially free of cellular material, viral material, or culture medium when produced by recombinant DNA techniques, or chemical precursors or other chemicals when chemically synthesized. Purity and homogeneity are typically determined using analytical chemistry techniques, for example, polyacrylamide gel electrophoresis or high performance liquid chromatography (HPLC). The term "purified" can denote that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. For a protein that can be subjected to modifications, for example, phosphorylation or glycosylation, different modifications may give rise to different isolated proteins, which can be separately purified. By "isolated polynucleotide" is meant a nucleic acid (e.g., a DNA) that is free of the genes which, in the naturally occurring genome of the organism from which the nucleic acid molecule of the invention is derived, flank the gene. The term therefore includes, for example, a recombinant DNA that is incorporated into a vector; into an autonomously replicating plasmid or virus; or into the genomic DNA of a prokaryote or eukaryote; or that exists as a separate molecule (for example, a cDNA or a genomic or cDNA fragment produced by PCR or restriction endonuclease digestion) independent of other sequences. In addition, the term includes an RNA molecule that is transcribed from a DNA molecule, as well as a recombinant DNA that is part of a hybrid gene encoding additional polypeptide sequence. By an "isolated polypeptide" is meant a polypeptide of the invention that has been separated from components that naturally accompany it. Typically, the polypeptide is isolated when it is at least 60%, by weight, free from the proteins and naturally occurring organic molecules with which it is naturally associated. In embodiments, the preparation is at least 75%, at least 90%, or at least 99%, by weight, a polypeptide of the invention. An isolated polypeptide of the invention may be obtained, for example, by extraction from a natural source, by expression of a recombinant nucleic acid encoding such a polypeptide; or by chemically synthesizing the protein. Purity can be measured by any appropriate method, for example, column chromatography, polyacrylamide gel electrophoresis, or by HPLC analysis. By "linker" is meant is meant a short amino acid or nucleic acid sequence that connects, respectively, two polypeptide or polynucleotide sequences. In an embodiment, a linker = In some embodiments, the linker comprises a self-cleaving peptide (e.g., P2A and or T2A). By "major histocompatibility complex (MHC) genes" is meant a linked set of genetic loci encoding proteins involved in antigen presentation to T cells. By "major histocompatibility complex proteins" is meant the polypeptides that function in antigen presentation to T cells. By "marker" is meant any protein, polynucleotide, or clinical feature having an alteration in expression level or activity that is associated with a disease or disorder. By "mutation" is meant an alteration in a nucleic acid sequence of a cell relative to a reference sequence. Mutations include the deletion, insertion, or rearrangement of sections of genes or chromosomes, as well as missense and nonsense mutations. A mutation may result in an alteration in a polypeptide product encoded by the mutated nucleic acid molecule. In some embodiments, a mutation in the p53 gene results in a p53 R175H mutation. Non-limiting examples of conservative substitutions of amino acids include substitutions made among amino acids within the following groups: (a) M, I, L, V; (b) F, Y, W; (c) K, R, H; (d) A, G; (e) S, T; (f) Q, N; and (g) E, D. In various embodiments, conservative amino acid substitutions can be made to the amino acid sequence of the proteins and polypeptides disclosed herein. By "nucleic acid," "nucleic acid molecule," or "polynucleotide" is meant a class of molecules that carry genetic information. Nucleic acids include DNA and RNA. Nucleic acids may be used to direct protein synthesis. As used herein, "obtaining" as in "obtaining an agent" includes synthesizing, purchasing, or otherwise acquiring the agent. By "operably linked" refers to a functional linkage between a regulatory sequence and a coding sequence, where a first polynucleotide is positioned adjacent to a second polynucleotide that directs transcription of the first polynucleotide when appropriate molecules (e.g., transcriptional activator proteins) are bound to the second polynucleotide. The described components are therefore in a relationship permitting them to function in their intended manner. For example, placing a coding sequence under regulatory control of a promoter means positioning the coding sequence such that the expression of the coding sequence is controlled by the promoter. By "portion" is meant a fragment of a polypeptide or nucleic acid molecule. This portion contains at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, or 90% of the entire length of the reference nucleic acid molecule or polypeptide. A fragment may contain 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, or 21 nucleotides. By "positioned for expression" is meant that the polynucleotide of the disclosure (e.g., a DNA molecule) is positioned adjacent to a DNA sequence that directs transcription and translation of the sequence (i.e., facilitates the production of, for example, a recombinant TCR and or fusion polypeptide described herein). The term "promoter" as used herein refers to a sequence of DNA that directs the expression (transcription) of a gene. A promoter may direct the transcription of a prokaryotic or eukaryotic gene. A promoter may be "inducible," initiating transcription in response to an inducing agent or, in contrast, a promoter may be "constitutive," whereby an inducing agent does not regulate the rate of transcription. A promoter may be regulated in a tissue-specific or tissue- preferred manner, such that it is only active in transcribing the operable linked coding region in a specific tissue type or types. In some embodiments, the promoter is an endogenous promoter (e.g., TRAC or TRBC promoter or the promoter that drives the expression of a gene located in a genomic safe harbor or other insertion site). In some embodiments, the promoter is a heterologous promoter. In some embodiments, the promoter is an elongation factor-1 alpha (EF- 1α) promoter. In some embodiments, the promoter is a Meiotic Nuclear Divisions 1 (MND1) promoter. By "polypeptide" or "amino acid sequence" is meant any chain of amino acids, regardless of length or post-translational modification. In various embodiments, the post-translational modification is glycosylation or phosphorylation. In various embodiments, conservative amino acid substitutions may be made to a polypeptide to provide functionally equivalent variants, or homologs of the polypeptide. In some aspects the disclosure embraces sequence alterations that result in conservative amino acid substitutions. In some embodiments, a "conservative amino acid substitution" refers to an amino acid substitution that does not alter the relative charge or size characteristics of the protein in which the conservative amino acid substitution is made. Variants can be prepared according to methods for altering polypeptide sequence known to one of ordinary skill in the art such as are found in references that compile such methods, e.g. Molecular Cloning: A Laboratory Manual, J. Sambrook, et al., eds., Second Edition, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989, or Current Protocols in Molecular Biology, F. M. Ausubel, et al., eds., John Wiley & Sons, Inc., New York. By "polynucleotide" or "nucleic acid molecule" is meant an oligomer or polymer of ribonucleic acid or deoxyribonucleic acid, or analog thereof. This term includes oligomers consisting of naturally occurring bases, sugars, and intersugar (backbone) linkages as well as oligomers having non-naturally occurring portions which function similarly. Such modified or substituted oligonucleotides are often preferred over native forms because of properties such as, for example, enhanced stability in the presence of nucleases. By "recombinant," "engineered," or "modified" is meant a nucleic acid, protein, peptide, cell, tissue, or organism produced by the combination of genetic material from at least two different sources. By "reduces" is meant a negative alteration of at least 10%, 25%, 50%, 75%, or 100%. By "reference" is meant a standard or control condition. In some embodiments, the reference is a healthy subject or cell. In some embodiments, the reference is an untreated subject or cell having a disease (e.g., a subject having a neoplasia or a neoplastic cell). In some embodiments, the reference is a p53 wildtype peptide or p53 peptide not comprising an R175 mutation. A "reference sequence" is a defined sequence used as a basis for sequence comparison. A reference sequence may be a subset of or the entirety of a specified sequence; for example, a segment of a full-length cDNA or gene sequence, or the complete cDNA or gene sequence. For polypeptides, the length of the reference polypeptide sequence will generally be at least about 16 amino acids, at least about 20 amino acids, at least about 25 amino acids, about 35 amino acids, about 50 amino acids, or about 100 amino acids. For nucleic acids, the length of the reference nucleic acid sequence will generally be at least about 50 nucleotides, at least about 60 nucleotides, at least about 75 nucleotides, at least about 100 nucleotides or at least about 300 nucleotides or any integer thereabout or therebetween. By "specifically binds" is meant a polynucleotide or polypeptide that recognizes and binds a target polypeptide or polynucleotide, but which does not substantially recognize and bind other molecules in a sample, for example, a biological sample, which naturally includes a polypeptides or polynucleotides described herein. In some embodiments, T cell receptors (TCRs) of the present disclosure specifically bind a p53 polypeptide comprising an R175 mutation (e.g., a R175H mutation), or a fragment thereof comprising the R175 mutation, and fail to detectably bind or bind at significantly lower levels to p53 polypeptides not including said mutation. Nucleic acid molecules useful in the methods of the invention include any nucleic acid molecule that encodes a polypeptide of the invention or a fragment thereof. Such nucleic acid molecules need not be 100% identical with an endogenous nucleic acid sequence but will typically exhibit substantial identity. Polynucleotides having "substantial identity" to an endogenous sequence are typically capable of hybridizing with at least one strand of a double- stranded nucleic acid molecule. By "hybridize" is meant pair to form a double-stranded molecule between complementary polynucleotide sequences (e.g., a gene described herein), or portions thereof, under various conditions of stringency. (See, e.g., Wahl, G. M. and S. L. Berger (1987) Methods Enzymol. 152:399; Kimmel, A. R. (1987) Methods Enzymol.152:507). For example, stringent salt concentration will ordinarily be less than about 750 mM NaCl and 75 mM trisodium citrate, less than about 500 mM NaCl and 50 mM trisodium citrate, and less than about 250 mM NaCl and 25 mM trisodium citrate. Low stringency hybridization can be obtained in the absence of organic solvent, e.g., formamide, while high stringency hybridization can be obtained in the presence of at least about 35% formamide, and at least about 50% formamide. Stringent temperature conditions will ordinarily include temperatures of at least about 30° C, at least about 37° C, and of at least about 42° C. Varying additional parameters, such as hybridization time, the concentration of detergent, e.g., sodium dodecyl sulfate (SDS), and the inclusion or exclusion of carrier DNA, are well known to those skilled in the art. Various levels of stringency are accomplished by combining these various conditions as needed. In an embodiment, hybridization will occur at 30° C in 750 mM NaCl, 75 mM trisodium citrate, and 1% SDS. In an embodiment, hybridization will occur at 37° C in 500 mM NaCl, 50 mM trisodium citrate, 1% SDS, 35% formamide, and 100 μg / ml denatured salmon sperm DNA (ssDNA). In an embodiment, hybridization will occur at 42° C in 250 mM NaCl, 25 mM trisodium citrate, 1% SDS, 50% formamide, and 200 μg / ml ssDNA. Useful variations on these conditions will be readily apparent to those skilled in the art. For most applications, washing steps that follow hybridization will also vary in stringency. Wash stringency conditions can be defined by salt concentration and by temperature. As above, wash stringency can be increased by decreasing salt concentration or by increasing temperature. For example, stringent salt concentration for the wash steps will be less than about 30 mM NaCl and 3 mM trisodium citrate, and less than about 15 mM NaCl and 1.5 mM trisodium citrate. Stringent temperature conditions for the wash steps will ordinarily include a temperature of at least about 25° C, of at least about 42° C, and of at least about 68° C. In an embodiment, wash steps will occur at 25° C in 30 mM NaCl, 3 mM trisodium citrate, and 0.1% SDS. In an embodiment, wash steps will occur at 42° C in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. In an embodiment, wash steps will occur at 68° C in 15 mM NaCl, 1.5 mM trisodium citrate, and 0.1% SDS. Additional variations on these conditions will be readily apparent to those skilled in the art. Hybridization techniques are well known to those skilled in the art and are described, for example, in Benton and Davis (Science 196:180, 1977); Grunstein and Hogness (Proc. Natl. Acad. Sci., USA 72:3961, 1975); Ausubel et al. (Current Protocols in Molecular Biology, Wiley Interscience, New York, 2001); Berger and Kimmel (Guide to Molecular Cloning Techniques, 1987, Academic Press, New York); and Sambrook et al., Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press, New York. By "substantially identical" is meant a polypeptide or nucleic acid molecule exhibiting at least 50% identity to a reference amino acid sequence (for example, any one of the amino acid sequences described herein) or nucleic acid sequence (for example, any one of the nucleic acid sequences described herein). In an embodiment, such a sequence is at least 60%, more preferably 80% or 85%, and 90%, 95% or even 99% identical at the amino acid level or nucleic acid to the sequence used for comparison. Sequence identity is typically measured using sequence analysis software (for example, Sequence Analysis Software Package of the Genetics Computer Group, University of Wisconsin Biotechnology Center, 1710 University Avenue, Madison, Wis.53705, BLAST, BESTFIT, GAP, or PILEUP / PRETTYBOX programs). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e-3and e-100indicating a closely related sequence. By "subject" is meant a mammal, including, but not limited to, a human or non-human mammal, such as a bovine, equine, canine, ovine, or feline. As used herein, the terms "treat," treating," "treatment," and the like refer to reducing or ameliorating a disorder and / or symptoms associated therewith. It will be appreciated that, although not precluded, treating a disorder or condition does not require that the disorder, condition or symptoms associated therewith be completely eliminated. As used herein "T cell" or "T lymphocyte" generally refers to an immune cell that matures in the thymus and expresses a T cell receptors(TCR). T cells can be naïve ("TN"; not exposed to antigen; increased expression of CD62L, CCR7, CD28, CD3, CD127, and CD45RA, and decreased or no expression of CD45RO as compared to TCM (described herein)), memory T cells (TM) (antigen experienced and long-lived), including stem cell memory T cells, and effector cells (antigen-experienced, cytotoxic). TM can be further divided into subsets of central memory T cells (TCM, expresses CD62L, CCR7, CD28, CD95, CD45RO, and CD127) and effector memory T cells (TEM, express CD45RO, decreased expression of CD62L, CCR7, CD28, and CD45RA). Effector T cells (TE) refers to antigen-experienced CD8+ cytotoxic T lymphocytes that express CD45RA, have decreased expression of CD62L, CCR7, and CD28 as compared to TCM, and are positive for granzyme and perforin. Helper T cells (TH) are CD4+ cells that influence the activity of other immune cells by releasing cytokines. CD4+ T cells can activate and suppress an adaptive immune response, and which of those two functions is induced will depend on presence of other cells and signals. T cells can be collected using suitable techniques, and the various subpopulations or combinations thereof can be enriched or depleted by suitable techniques, such as by affinity binding to antibodies, flow cytometry, or immunomagnetic selection. Other example T cells include regulatory T cells, such as CD4+ CD25+ (Foxp3+) regulatory T cells and Treg17 cells, as well as Tr1, Th3, CD8+CD28-, and Qa- 1 restricted T cells. As used herein, a "T cell receptor" (TCR) generally refers to an immunoglobulin superfamily member having a variable binding domain, a constant domain, a transmembrane region, and a short cytoplasmic tail; see, e. g., Janeway et al., Immunobiology: The Immune System in Health and Disease, 3rd Ed., Current Biology Publications, p.433, 1997) capable of specifically binding to an antigen peptide bound to a MHC receptor. A TCR can be found on the surface of a cell or in soluble form and generally comprises heterodimer having α and β chains (also known as TCR α and TCRβ, respectively), or γ and δ chains (also known as TCRγ and TCRδ, respectively). In some embodiments, the TCR specifically binds a p53 polypeptide having an R175 mutation (e.g., an R175H mutation). In some embodiments, the TCR specifically binds a peptide bound to an HLA-A*02 MHC molecule (e.g., an HLA-A*02:01 MHC molecule). As used herein, a "TCR-T cell" refers to a T cell that comprises an exogenous nucleic acid sequence encoding a heterologous TCR. In some embodiments, the T cell further comprises an exogenous nucleic acid sequences encoding one or more additional heterologous or recombinant proteins. The heterologous TCR confers specificity on the TCR-T cell for a cognate peptide of interest (e.g., a peptide associated with a disease or disorder, such as cancer (e.g., a p53 R175H peptide). The term "variable region" or "variable domain" generally refers to the domain of an immunoglobulin superfamily binding protein (e.g., a TCR α-chain or β-chain (or γ chain and δ chain for γδ TCRs)) that is involved in binding of the immunoglobulin superfamily binding protein (e.g., TCR) to antigen. The variable domains of the α chain and β chain (Vα and Vβ, respectively) of a native TCR generally have similar structures, with each domain comprising four generally conserved framework regions (FRs) and three CDRs. The Vα domain is encoded by two separate DNA segments, the variable gene segment and the joining gene segment (V-J); the Vβ domain is encoded by three separate DNA segments, the variable gene segment, the diversity gene segment, and the joining gene segment (V-D-J). A single Vα or Vβ domain may be sufficient to confer antigen-binding specificity. Furthermore, TCRs that bind a particular antigen may be isolated using a Vα or Vβ domain from a TCR that binds the antigen to screen a library of complementary Vα or Vβ domains, respectively. A "vector" as used herein, generally refers to a macromolecule or association of macromolecules that comprises or associates with a polynucleotide and that may be used to mediate delivery of the polynucleotide to a cell. Examples of vectors include plasmids, viral vectors, liposomes, and other gene delivery vehicles. The vector generally comprises genetic elements, e.g., regulatory elements, operatively linked to a gene to facilitate expression of the gene in a target. In some embodiments, the vector is a viral vector (e.g., a lentiviral or adeno- associated virus vector). In some embodiments, the vector is a gene cassette (e.g., for non-viral knock-in). Unless specifically stated or obvious from context, as used herein, the term "or" is understood to be inclusive. Unless specifically stated or obvious from context, as used herein, the terms "a," "an," and "the" are understood to be singular or plural. Ranges provided herein are understood to be shorthand for all of the values within the range. For example, a range of 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting 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, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50. Unless specifically stated or obvious from context, as used herein, the term "about" is understood as within a range of normal tolerance in the art, for example within 2 standard deviations of the mean. About can be understood as within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise clear from context, all numerical values provided herein are modified by the term about. The recitation of a listing of chemical groups in any definition of a variable herein includes definitions of that variable as any single group or combination of listed groups. The recitation of an embodiment for a variable or aspect herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. Any compositions or methods provided herein can be combined with one or more of any of the other compositions and methods provided herein. BRIEF DESCRIPTION OF THE DRAWINGS FIG.1 provides a graph showing the percentage of isolated T cells modified with nucleic acid molecules encoding the variable alpha and beta chains of one of exogenous TCRs 1-12, the variable alpha and beta chains of one of exogenous TCRs 1-12 that have been modified to comprise a cysteine residue, or the variable alpha and beta chains of one of exogenous TCRs 1- 12 and a CD8αβ coreceptor. "UTD" denotes untransduced. The asterisk denotes a vendor error in synthesis of a vector resulting in low transduction. FIG.2 provides graphs comparing MHC-peptide binding by CD4+ and CD8+ T cells modified to express one of exogenous TCRs 1-12 alone or MHC-peptide binding by T cells modified to express one of exogenous TCRs 1-12 and a CD8αβ coreceptor. Binding was measured by tetramer staining followed by flow cytometry quantifying tetramer mean fluorescence intensity (MFI). FIGs.3A-3B provide graphs showing the activation by the index peptide of CD4+and CD8+T cells modified to express an exogenous TCR and a CD8αβ coreceptor or only an exogenous TCR, respectively, as measured by the percentage of the T cells expressing CD137. FIG.3A shows the activation of cells modified to express one of TCRs 1-6. FIG.3B shows the activation of cells modified to express one of cells 7-12 (data for TCR8 in CD4 T cells is not shown). FIGs.4A-4B provide graphs showing T cell mediated killing of two tumor cell lines. FIG.4A shows T cell mediated killing of two tumor cell lines (TYK-nu, a human ovarian cancer cell line, and KLE, an endometrial tumor cell line, both at a 5:1 effector to target cell ratio) by T cells modified to express one of exogenous TCRs 1-6. TYK-nu and KLE cells were modified to express a red fluorescent protein, which was measured by live cell imaging using the IncuCyte S3 microscope and software package, and total red object integrated intensity ("Tumor Confluence") is plotted over time as a measure of tumor cell confluence. FIG.4B shows T cell mediated killing of two tumor cell lines (TYK-nu and KLE, both at a 5:1 effector to target cell ratio) by T cells modified to express one of exogenous TCRs 7, 9, 10, 11, or 12. Tumor cell killing was measured in the same manner as described for FIG.4A. FIG.5 provides graphs showing T cell mediated killing of two tumor cell lines (TYK-nu and KLE, both at a 3:1 effector to target cell ratio) by T cells modified by non-viral knock-in at the TRAC locus of constructs encoding one of exogenous TCRs 2, 3, 5, 6, 9, or 12 and by knockout of the TRBC. Tumor confluence was measured in the same manner as described for FIG.4A. FIGs.6A-6B provide graphs showing that T cells modified to express one of exogenous TCRs 2, 3, 6, or 9 recognize p53 R175H mutant peptide but not wild type p53. FIG.6A shows IFNγ expression of T cells modified to express one of exogenous TCRs 2, 3, 6, or 9 after co- culture with T2 cells expressing an empty MHC loaded with either mutant or wild type p53 peptide. FIG.6B shows that T cells expressing one of TCRs 2, 3, 5, 6, 9, or 12 do not control tumor growth after co-culture with tumor cell line CFPAC, a ductal adenocarcinoma cell line, which expresses an HLA-A2 / A3 MHC molecule and a p53 C242R mutant peptide (but not an R175H one), at a 10:1 effector to target cell ratio. Tumor confluence was measured in the same manner as described for FIG.4A. FIGs.7A and 7B illustrate that T cells modified to express exogenous TCR9 do not recognize off-target peptides. FIG.7A provides graphs showing that T cells modified to express exogenous TCR9 and recognize peptides comprising an R175H mutation do not recognize, and are not activated by, off-target peptides. Specifically, the TCR-T cells were co-cultured with T2 cells loaded with potential off-target peptides identified using either a 20% or 10% cut-off in the TCR motif derived from the XScan and IFNg was measured. FIG.7B is a graph showing that only at very high concentrations of four potential off-target peptides were TCR-T cells induced to express IFNγ. FIGs.8A-8D provides graphs demonstrating that a dual armoring strategy comprising an interleukin receptor (IR) and a Fas-41BB (FasBB) fusion peptide increases yield and maintains transgene expression in modified TCR-T cells. FIG.8A is a graph showing the percentage of cells that were successfully modified by knock-in to the TRAC locus constructs encoding TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB fusion proteins. As used herein, "FasBB" refers to a fusion protein comprising an extracellular domain of a Fas ligand receptor and an intracellular signaling domain of 41BB. The cells were also modified to knock-out TRBC (i.e., the cells were double knockouts). FIG.8B shows the mean fluorescence intensity (MFI) detected after staining double knock out cells modified to express ILR or FasBB or ILR and FasBB with labeled tetramer, Fas mAb, or ILR-specific mAb. FIG.8C is a graph showing the percentage of cells that were successfully modified by knock-in to the TRAC locus constructs encoding TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB fusion proteins. These cells are single knockouts as the TRAC locus was knocked out by insertion of the construct, but TRBC was not disrupted. FIG.8D provides graphs showing MFI detected after staining single knockout cells modified to express TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB with labeled tetramer, Fas mAb, or ILR-specific mAb. FIGs.9A-9B provide graphs demonstrating that TCR-T cells expressing exogenous TCR9 and CD8αβ coreceptor and ILR or FasBB or ILR and FasBB are sensitive to p53 R175H mutant peptide. FIG.9A shows IFNγ detected in a coculture of modified TCR-T cells and T2 cells loaded with p53 R175H peptide. FIG.9B shows the percentage of TCR-T cells expressing CD137 after coculture with T2 cells loaded with p53 R175H mutant peptide. FIGs.10A-10E demonstrates TCR-T mediated specific killing of two tumor cell lines (TYK-nu (FIG.10A) and KLE (FIG.10B), both at a 3:1 effector to target cell ratio). FIG.10A is a graph showing cytotoxic activity against TYK-nu cells by double knockout TCR-T cells (i.e., modified by knockout of the TRBC and by non-viral knock-in at the TRAC locus of constructs encoding TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB). FIG.10B is a graph showing the cytotoxic activity against KLE cells by the double knockout TCR-T cells described in FIG.10A. FIG.10C is a graph showing cytotoxic activity against TYK-nu cells by single knockout TCR-T cells (i.e., modified by non-viral knock-in at the TRAC locus of constructs encoding TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB). FIG.10D is a graph showing the cytotoxic activity against KLE cells by the single knockout TCR-T cells described in FIG.10C. FIG.10E is a graph showing that the TCR-T cells described in FIG.10C do not control tumor growth after co-culture with tumor cell line CFPAC. For FIGs.10A-10E, tumor confluence was measured in the same manner as described for FIG.4A. FIGs.11A-11D demonstrates the persistence of TCR-T cells at the conclusion of a study of TCR-T cytotoxicity assay. FIG.11A is a graph showing the number of double knockout TCR- T cells (as described in FIG.10A) per well remaining after co-incubation with TYK-nu cells at a 10:1 effector to target cell ratio. FIG.11B is a graph showing the number of double knockout TCR-T cells (as described in FIG.10A) per well remaining after co-incubation with KLE cells at a 10:1 effector to target cell ratio. FIG.11C is a graph showing the number of single knockout TCR-T cells (as described in FIG.10C) per well remaining after co-incubation with TYK-nu cells at a 10:1 effector to target cell ratio). FIG.11D is a graph showing the number of single knockout TCR-T cells (as described in FIG.10C) per well remaining after co-incubation with KLE cells at a 10:1 effector to target cell ratio). FIGs.12A-12F provide graphs demonstrating that TCR-T cells modified to express TCR9, CD8αβ coreceptor, ILR, and FasBB are activated when co-cultured with a tumor cell line presenting a p53 R175H peptide in an HLA-A*02 context. FIG.12A shows IFNγ and GrzB levels after co-culture with double knockout TCR-T cells modified to express TCR9 and CD8αβ coreceptor and KLE tumor cells (HLA-A*02, p53 R175H+). FIG.12B shows IFNγ and GrzB levels after co-culture with double knockout TCR-T cells modified to express TCR9 and CD8αβ coreceptor and LS123 cells (HLA-A*3 / 24, p53 R175H+). FIG.12C, FIG.12D, FIG.12E, and FIG.12F show IFNγ, TNFα, IL-2, and GrzB levels, respectively, after co-culture with single knockout TCR-T cells modified to express TCR9, CD8αβ coreceptor, an ILR fusion protein, and a FasBB switch receptor. FIG.13 provides graphs showing that TCR-T cells modified to express TCR9 and CD8αβ coreceptor with or without ILR and FasBB fail to kill tumor cells that do not express HLA-A*02 and p53 R175H. HCT116 cells, a colon cancer cell line, express HLA-A*02 and wild type p53. SaOS2 cells express HLA-A*02 and are p53 negative cells. Tumor confluence was measured in the same manner as described for FIG.4A. FIGs.14A and 14B demonstrate that a FasBB switch receptor provides protection against Fas ligand-mediated cell death. FIG.14A is a graph showing the percentage of dead unengineered T cells incubated at increasing concentrations of recombinant Fas ligand. FIG. 14B is a graph showing TCR-T cells modified to express TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB after exposure to Fas ligand (FASL), demonstrating that FasBB prevented Fas ligand-induced death of TCR-T cells. Dead cells were labeled with Zombie NIR (SONY Biotechnology, San Jose, CA), an amine reactive fluorescent dye that is non-permeant to live cells but permeant to cells with compromised cell membranes. Labeled cells were detected by flow cytometry (gated on 2A expression; 2A is a self-cleaving peptide encoded on the knock- in construct). FIG.15A and 15B are graphs showing TCR-T cell mediated killing of TYK-nu tumor cells (parent or engineered to express FASL) at a 3:1 effector to target cell ratio by TCR-T cells modified by knockout of the TRBC and by non-viral knock-in at the TRAC locus of constructs encoding TCR9, CD8αβ coreceptor, and ILR, FasBB, or ILR and FasBB. Tumor confluence was measured in the same manner as described for FIG.4A. FIGs.16A-16C illustrate that the TCR-T cells of the present disclosure are not viable in culture lacking cytokines. FIG.16A provides a graph comparing the number of viable double knockout TCR-T cells over the course of 30 days cultured in media with or without interleukin 2 (IL2), interleukin 7 (IL7), and interleukin 15 (IL15). FIG.16B is a graph comparing the number of viable single knockout TCR-T cells over the course of 30 days cultured in media with or without interleukin 2 (IL2), interleukin 7 (IL7), and interleukin 15 (IL15). FIG.16C is a graph showing that, regardless of armoring, in the presence or absence of Fas ligand single knockout TCR-T expressing TCR9, CD8αβ coreceptor, an ILR fusion protein, and a FasBB switch receptor are not viable in vitro in the absence of cytokines. FIGs.17A and 17B provide graphs showing tumor volume in mice having a TYK-nu subcutaneous xenograft and either treated with non-engineered T cells or TCR-T cells engineered to express TCR9, CD8αβ coreceptor, and ILR and FasBB. The inset shows animal weight for these same mice across the same timepoints as the larger graph. FIG.18 provides graphs showing enrichment of TCR-T cells co-expressing a TCR disclosed herein with a FasBB fusion protein as compared to cells not expressing the FasBB fusion protein with increasing concentrations of Fas ligand (rhFASL). DETAILED DESCRIPTION OF THE INVENTION The disclosure features engineered TCR-T cells and methods of using such cells for treating neoplasias. The disclosure is based, at least in part, on the discovery that engineered T cells expressing a T cell receptor (TCR) that specifically binds a p53 peptide comprising an R175H mutation can be used to kill neoplastic cells. Advantageously, these T cells are also engineered to express a CD8 transmembrane glycoprotein ("CD8αβ" or "CD8ab") that acts as co-receptor during T cell antigen engagement to enhance T cell activation, a FasBB switch receptor (e.g., FAS extracellular domain fused to 41BB intracellular signaling domain) that converts inhibitory Fas ligand (FasL) signals to activating or proliferatory signals , and / or a cytokine modulator, such as IL7Rα or a fusion protein comprising a cytokine (e.g., IL7Rα) intracellular domain or a portion thereof capable of generating cytokine signaling. In some embodiments, the T cell comprises further alterations (e.g., genetic modifications) or expresses additional exogenous peptides or fusion proteins that improve T cell persistence, reduce and / or prevent T cell exhaustion, or that reduce the engineered T cell’s immunogenicity. Oncogenic driver protein: mutant p53. Mutations of the Tp53 gene are the most frequently observed genetic changes in human cancers; often leading to an overexpression of the wild type (wt) p53 protein. The immunogenicity of p53 mutations in cancer patients has been demonstrated by the detection of T cell responses against several p53 neoantigens, most notably R175H in which arginine at position 175 is replaced by histidine. This driver mutation is the most frequently observed mutation in TP53. A number of T cell receptors (TCRs) have been isolated from tumor infiltrating lymphocytes (TILs) of epithelial cancer patients that target a neoepitope (the cognate peptide of the TCR) corresponding to residues 168 to 176 of p53 R175H (HMTEVVR[H]C; wherein the bracketed histidine amino acid is the mutant amino acid). In some embodiments, the present disclosure provides TCRs that specifically bind to a mutant p53 peptide in a peptide:HLA complex (e.g., a p53 R175H:HLA-A*02 complex). In some embodiments, the present disclosure provides TCRs that specifically bind a mutant p53 peptide in a peptide:HLA complex, where the mutant p53 peptide comprises the amino acid sequence HMTEVVRHC. Host cells The disclosure provides host cells (e.g., engineered immune cells) and populations thereof that comprise, encode, and / or are capable of expressing a binding protein disclosed herein. In some aspects, the present disclosure provides a host cell comprising a binding protein that binds a peptide:HLA complex, wherein the peptide comprises a p53 R175H mutant peptide. In some embodiments, the peptide:HLA complex comprises an HLA-A*02 allele. In some embodiments, the peptide:HLA complex comprises an HLA-A*02:01 allele. In some embodiments, the peptide:HLA complex comprises an HLA allele that binds or is predicted to bind a p53 mutant peptide (e.g., the p53 mutant peptide, such as R175H) with a suitable affinity for presentation and TCR activation, for example, a binding affinity or KD of at most 1000 nM, at most 750 nM, at most 500 nM, at most 250 nM, at most 100 nM, at most 50nM, or at most 10 nM. In some embodiments, the host cell comprises an immune cell or a precursor thereof. In some cases, the immune cell comprises a T cell, a NK cell, a NK-T cell, a dendritic cell, a macrophage, a monocyte, or any combination thereof. In some cases, the immune cell is a T cell, wherein the T cell comprises a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a CD4+ CD8+ double positive T cell, a γδ T cell, or any combination thereof. In some cases, the host cell further comprises a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor α (CD8α) chain or a polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor β (CD8β) chain. In some cases, when the host cell is in the presence of a tumor cell that expresses a p53 R175H mutant peptide, CD137 expression of the host cell is elevated as compared to: (i) CD137 expression by a reference human T cell not expressing the binding protein, when the reference human T cell is in the presence of the tumor cell; or (ii) CD137 expression by the human T cell expressing the binding protein when not in the presence of the tumor cell or when not in the presence of an antigen-presenting cell expressing a peptide:HLA complex. A host cell can be a peripheral blood mononuclear cell (PBMC). A host cell can be a lymphoid cell. A host cell can be a lymphocyte. A host cell can be a T cell. A host cell can be a B cell. A host cell can be a natural killer (NK) cell. A host cell can be a Natural Killer T (NKT) cell. A host cell can be a mammalian cell. A host cell can be a human cell. A host cell can be a primary cell. A host cell can be an immortalized cell. A host cell can be of a cell line. A host cell can be differentiated from a stem cell, for example, an induced pluripotent stem cell (iPSC), embryonic stem cell, hematopoietic stem cell (HSC), or the like. In some cases, the host cells are "off-the-shelf" cells that are engineered from an immune cell line, for instance, a T cell line or an NK cell line (e.g., NK-92, or e.g., NK-YS, KHYS-1, NKL, NKG, SNK-6, or IMC-1). Such host cells can be readily available and formulated for direct administration to a subject in need thereof. A host cell can be allogenic to a subject or patient. In some embodiments, a host cell is autologous to a subject or patient. For example, immune cells (e.g., T cells) can be obtained from a subject or patient and modified ex vivo to generate a host cell comprising a TCR that specifically binds a p53 R175H mutant peptide. A host cell can be an alpha beta T cell. A host cell can be a gamma delta T cell. In some embodiments, a host cell comprises a disruption or deletion of one or more endogenous TCR- encoding genes, such as TRAC, TRB (e.g., TRBC1 and / or TRBC2), TRG, and / or TRD. In some embodiments, a host cell comprises a disruption or deletion of a variable region of one or more endogenous TCR-encoding genes, such as a disruption or deletion in TRAC, TRB, TRG, and / or TRD. In some embodiments, a host cell comprises a disruption or deletion of a constant region of one or more endogenous TCR-encoding genes. Host cells expressing a binding protein according to the present disclosure are activated (e.g., as determined by expression of CD137 or IFNg) in the presence of a neoantigen to which the binding protein recognizes. For example, a binding protein that recognizes and binds a mutant p53 peptide (e.g., in complex with HLA-A*02, for example) is activated in the presence of mutant p53-expressing cancer cell lines (e.g., TYK-nu (overian cancer cell line), KLE (endometrial carcinoma cell line). In some embodiments, a host cell described herein can bind to and specifically kill a target cell expressing a neoantigen (e.g., mutant p53-expressing cells) in vitro when co-incubated with the target cell at a 10:1, 5:1, 2:1, or a 1:1 effective-to-target cell ratio. Binding protein In some embodiments, the present disclosure provides for a binding protein wherein the binding protein is capable of binding to a peptide:HLA complex, wherein the peptide comprises a p53 R175H mutant peptide. In some embodiments, the peptide:HLA complex comprises an HLA-A*02 allele. In some embodiments, the peptide:HLA complex comprises an HLA- A*02:01 allele. In some embodiments, the peptide:HLA complex comprises an HLA allele that binds or is predicted to bind a p53 mutant peptide (e.g., an R175 mutant peptide, such as R175H) with a suitable affinity for presentation and TCR activation, for example, a binding affinity or KDof at most 1000 nM, at most 750 nM, at most 500 nM, at most 250 nM, at most 100 nM, at most 50 nM, or at most 10 nM. The binding protein can comprise a TCR or a portion thereof. In some embodiments, the binding protein comprises a T cell receptor (TCR) α chain variable (Vα) region, a TCR β chain variable (Vβ) region, a T cell receptor (TCR) α chain constant (Cα) region, and / or a T cell receptor (TCR) β chain constant (Cβ) region. The binding protein can also comprise a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region, or a combination thereof. The binding protein can comprise a component of a TCR signaling complex, for example, an extracellular domain, transmembrane domain, and / or cytoplasmic domain of a TCR signaling complex, such as a human TCR signaling complex. The binding protein can comprise (i) an extracellular domain of TCR alpha chain constant region, TCR beta chain constant region, TCR gamma chain constant region, or TCR delta chain constant region; (ii) a transmembrane domain of TCR alpha chain, TCR beta chain, TCR gamma chain, or TCR delta chain; and / or (iii) a cytoplasmic domain of TCR alpha chain, TCR beta chain, TCR gamma chain, or TCR delta chain. The binding protein can comprise a full length or substantially full length TCR alpha chain, TCR beta chain, TCR gamma chain, and / or TCR delta chain. In some cases, the binding protein comprises a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising a sequence having at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or 100% sequence identity to any of the TCR Vα, Vβ, FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 sequences described in Table 1. A binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region disclosed herein can comprise, consist essentially of, or consist of an amino acid sequence with at least about 70%, at least about 71%, at least about 72%, at least about 73%, at least about 74%, at least about 75%, at least about 76%, at least about 77%, at least about 78%, at least about 79%, at least about 80%, at least about 81%, at least about 82%, at least about 83%, at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 95.5%, at least about 96%, at least about 96.5%, at least about 97%, at least about 97.5%, at least about 98%, at least about 98.5%, at least about 99%, at least about 99.5%, or about 100% sequence identity or sequence similarity to any one of the TCR Vα, Vβ, FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 sequences disclosed in Table 1. A binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region disclosed herein can comprise, consist essentially of, or consist of an amino acid sequence with at most about 70%, at most about 71%, at most about 72%, at most about 73%, at most about 74%, at most about 75%, at most about 76%, at most about 77%, at most about 78%, at most about 79%, at most about 80%, at most about 81%, at most about 82%, at most about 83%, at most about 84%, at most about 85%, at most about 86%, at most about 87%, at most about 88%, at most about 89%, at most about 90%, at most about 91%, at most about 92%, at most about 93%, at most about 94%, at most about 95%, at most about 95.5%, at most about 96%, at most about 96.5%, at most about 97%, at most about 97.5%, at most about 98%, at most about 98.5%, at most about 99%, or at most about 99.5% sequence identity or sequence similarity to any one of the TCR Vα, Vβ, FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 sequences disclosed in Table 1. In some embodiments, a binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises, consists essentially of, or consists of an amino acid sequence with 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 95.5%, about 96%, about 96.5%, about 97%, about 97.5%, about 98%, about 98.5%, about 99%, about 99.5% or about 100% sequence identity or sequence similarity to any one of the TCR Vα, Vβ, FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 sequences disclosed in Table 1. The degree of sequence identity between two sequences can be determined, for example, by comparing the two sequences using computer programs designed for this purpose, such as global or local alignment algorithms. Non-limiting examples include BLASTp, BLASTn, Clustal W, MAFFT, Clustal Omega, AlignMe, Praline, GAP, BESTFIT, Needle (EMBOSS), Stretcher (EMBOSS), GGEARCH2SEQ, Water (EMBOSS), Matcher (EMBOSS), LALIGN, SSEARCH2SEQ, or another suitable method or algorithm. A global alignment algorithm, such as a Needleman and Wunsch algorithm, can be used to align two sequences over their entire length, maximizing the number of matches and minimizes the number of gaps. Default settings can be used. To generate similarity scores for two amino acid sequences, scoring matrices can be used that assign positive scores for some non-identical amino acids (e.g., amino acids with similar physio-chemical properties and / or amino acids that exhibit frequent substitutions in orthologs, homologs, or paralogs), Non-limiting examples of scoring matrices include PAM30, PAM70, PAM250, BLOSUM45, BLOSUM50, BLOUM62, BLOSUM80, and BLOSUM90. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises, consists essentially of, or consists of the amino acid sequence of any one of the TCR Vα, Vβ, FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 sequences disclosed in Table 1. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises an amino acid sequence with one or more insertions, deletions, and / or substitutions relative to any one of the sequences disclosed in Table 1. For example, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region can comprise an amino acid sequence with at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, or at least 30 amino acid insertions relative to any one of the sequences disclosed in Table 1. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises an amino acid sequence with at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, at most 11, at most 12, at most 13, at most 14, at most 15, at most 16, at most 17, at most 18, at most 19, at most 20, at most 25, at most 30, at most 35, at most 40, at most 45, or at most 50 amino acid insertions relative to any one of the sequences disclosed in Table 1. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 amino acid insertions relative to any one of the sequences disclosed in Table 1. The one or more insertions can be at the N-terminus, the C-terminus, within the amino acid sequence, or a combination thereof. The one or more insertions can be contiguous, non- contiguous, or a combination thereof. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises an amino acid sequence with at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, or at least 30 amino acid deletions relative to any one of the sequences disclosed in Table 1. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises an amino acid sequence with at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, at most 11, at most 12, at most 13, at most 14, at most 15, at most 16, at most 17, at most 18, at most 19, at most 20, at most 25, at most 30, at most 35, at most 40, at most 45, or at most 50 amino acid deletions relative to any one of the sequences disclosed in Table 1. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 amino acid deletions relative to any one of the sequences disclosed in Table 1. The one or more deletions can be at the N-terminus, the C-terminus, within the amino acid sequence, or a combination thereof. The one or more deletions can be contiguous, non- contiguous, or a combination thereof. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises an amino acid sequence with at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, at least 8, at least 9, at least 10, at least 11, at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, at least 20, at least 25, or at least 30 amino acid substitutions relative to any one of the sequences disclosed in Table 1. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises an amino acid sequence with at most 1, at most 2, at most 3, at most 4, at most 5, at most 6, at most 7, at most 8, at most 9, at most 10, at most 11, at most 12, at most 13, at most 14, at most 15, at most 16, at most 17, at most 18, at most 19, at most 20, at most 25, at most 30, at most 35, at most 40, at most 45, or at most 50 amino acid substitutions relative to any one of the sequences disclosed in Table 1. In some embodiments, the binding protein, a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, or 50 amino acid substitutions relative to any one of the sequences disclosed in Table 1. In some embodiments, the binding protein is a TCR comprising an alpha chain and a beta chain, each comprising a variable region: variable alpha (Vα) region and a variable beta (Vβ) region. The Vα and Vβ regions of the binding protein each comprise three complementary determining regions (CDR): CDR1, CDR2, and CDR3. In some embodiments, the Vα region of the binding protein comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 2, 22, 42, 62, 82, 102, 122, 142, 162, 182, 202, or 222. In some embodiments, the Vα region of the binding protein comprises a CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 4, 24, 44, 64, 84, 104, 124, 144, 164, 184, 204, or 224. In some embodiments, the Vα region of the binding protein comprises a CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 6, 26, 46, 66, 86, 106, 126, 146, 166, 186, 206, or 226. In some embodiments, the Vα region of the binding protein comprises a CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NO: 2, 4, and 6, respectively; 22, 24, and 26, respectively; 42, 44, and 46, respectively; 62, 64, and 66, respectively; 82, 84, and 86, respectively; 102, 104, and 106, respectively; 122, 124, and 126, respectively; 142, 144, and 146, respectively; 162, 164, and 166, respectively; 182, 184, and 186, respectively; 202, 204, and 206, respectively; or 222, 224, and 226, respectively. In some embodiments, the Vα region of the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228. In some embodiments, the alpha chain of the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 9, 29, 49, 69, 89, 109, 129, 149, 169, 189, 209, or 229. In some embodiments, the alpha chain of the binding protein is encoded by a nucleic acid molecule comprising the sequence set forth in SEQ ID NO: 10, 30, 50, 70, 90, 110, 130, 150, 170, 190, 210, or 230. In some embodiments, the Vβ region of the binding protein comprises a CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 12, 32, 52, 72, 92, 112, 132, 152, 172, 192, 212, or 232. In some embodiments, the Vβ region of the binding protein comprises a CDR2 comprises the amino acid sequence set forth in SEQ ID NO: 14, 34, 54, 74, 94, 114, 134, 154, 174, 194, 214, or 234. In some embodiments, the Vβ region of the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 16, 36, 56, 76, 96, 116, 136, 156, 176, 196, 216, or 236. In some embodiments, the Vβ region of the binding protein comprises a CDR1, CDR2, and CDR3 comprising the amino acid sequences of SEQ ID NO: 12, 14, and 16, respectively; 32, 34, and 36, respectively; 52, 54, and 56, respectively; 72, 74, and 76, respectively; 92, 94, and 96, respectively; 112, 114, and 116, respectively; 132, 134, and 136, respectively; 152, 154, and 156, respectively; 172, 174, and 176, respectively; 192, 194, and 196, respectively; 212, 214, and 216, respectively; or 232, 234, and 236, respectively. In some embodiments, the Vβ region of the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238. In some embodiments, the beta chain of the binding protein comprises the amino acid sequence set forth in SEQ ID NO: 19, 39, 59, 79, 99, 119, 139, 159, 179, 199, 219, or 239. In some embodiments, the beta chain of the binding protein is encoded by a nucleic acid molecule comprising the sequence set forth in SEQ ID NO: 20, 40, 60, 80, 100, 120, 140, 160, 180, 200, 220, or 240. Table 1 Table 2 The one or more substitutions can be at the N-terminus, the C-terminus, within the amino acid sequence, or a combination thereof. The one or more substitutions can be contiguous, non- contiguous, or a combination thereof. In some embodiments, the one or more substitutions are conservative. In some embodiments, the one or more substitutions are non-conservative. In some cases, the binding protein comprises a TCR α chain; a TCR β chain; a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region that is human, humanized, or chimeric. In some cases, the cognate peptide of the binding protein is a p53 mutant peptide. In some embodiments, the p53 mutant peptide is a p53 R175H mutant peptide. In some cases, the p53 mutant peptide comprises the amino acid sequence HMTEVVRHC. In some cases, the binding protein is selective for the p53 R175H mutant peptide, e.g., specifically, selectively or preferentially binds the p53 R175H mutant peptide. In some cases, the binding protein is at least 2-, 3-, 5-, 10-, 25-, 50-, 100-, 200-, 500-, 1000-, 2000-, 3000-, 4000-, 5000- fold, or 10,000-fold selective for the p53 R175H mutant peptide versus other 10-mer peptides, for example, a corresponding wild type peptide, or a peptide encoded by a genome of the cell (e.g., that binds to a different p53 R175H-specific TCR, or that is predicted to exhibit off-target binding to the binding protein). In some cases, the binding protein has a log10 EC50 for the p53 R175H mutant peptide of about -6.0 or less, about -6.1 or less, about -6.2 or less, about -6.3 or less, about -6.4 or less, about -6.5 or less, about -6.6 or less, about -6.7 or less, about -6.8 or less, about -6.9 or less, about -7.0 or less, about -7.1 or less, about -7.2 or less, about -7.3 or less, about -7.4 or less, about -7.5 or less, about -7.6 or less, about -7.7 or less, about -7.8 or less, about -7.9 or less, about -8.0 or less, about -8.1 or less, about -8.2 or less, about -8.3 or less, about -8.4 or less, about -8.5 or less, about -8.6 or less, about -8.7 or less, about -8.8 or less, about -8.9 or less, about -9 or less, about -9.1 or less, or about -9.2 or less. In some embodiments, a host cell disclosed herein comprises a binding protein (e.g., TCR) that binds a target antigen of the binding protein (for example, a p53 R175H mutant peptide, such as p53 R175H mutant peptide, e.g., present in a peptide:HLA complex) with an EC50 (e.g., peptide dose at which a half-maximal activation of a T cell population is reached) of less than about 100 mM, less than about 10 mM, less than about 1 mM, less than about 500 μM, less than about 100 μM, less than about 50 μM, less than about 10 μM, less than about 5 μM, less than about 4 μM, less than about 3 μM, less than about 2 μM, less than about 1 μM, less than about 900 nM, less than about 800 nM, less than about 700 nM, less than about 600 nM, less than about 500 nM, less than about 400 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 5 nM, less than about 1 nM, less than about 500 pM, or less than about 100 pM. The host cell can comprise, for example, a modification (e.g., genomic mutation) that results in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2, or a combination thereof. The binding protein can be a TCR that comprises a Vα and Vβ regions and / or CDRs disclosed herein. In some embodiments, a host cell disclosed herein comprises a binding protein (e.g., TCR) that binds a target antigen of the binding protein (for example, a p53 R175H mutant peptide, such as p53 R175H mutant peptide, e.g., present in a peptide:HLA complex) with an EC50(e.g., peptide dose at which a half-maximal activation of a T cell population is reached) of at least about 100 mM, at least about 10 mM, at least about 1 mM, at least about 500 μM, at least about 100 μM, at least about 50 μM, at least about 10 μM, at least about 5 μM, at least about 4 μM, at least about 3 μM, at least about 2 μM, at least about 1 μM, at least about 900 nM, at least about 800 nM, at least about 700 nM, at least about 600 nM, at least about 500 nM, at least about 400 nM, at least about 300 nM, at least about 200 nM, at least about 100 nM, at least about 90 nM, at least about 80 nM, at least about 70 nM, at least about 60 nM, at least about 50 nM, at least about 40 nM, at least about 30 nM, at least about 20 nM, at least about 10 nM, at least about 5 nM, at least about 1 nM, at least about 500 pM, at least about 100 pM. The host cell can comprise, for example, a modification (e.g., genomic mutation) that results in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2, or a combination thereof. The binding protein can be a TCR that comprises a Vα and Vβ regions and / or CDRs disclosed herein. In some embodiments, a binding protein (e.g., TCR) binds a target (for example, a p53 R175H mutant peptide, such as p53 R175H mutant peptide, e.g., present in a peptide:HLA complex) with a KD of less than about 100 mM, less than about 10 mM, less than about 1 mM, less than about 500 μM, less than about 100 μM, less than about 50 μM, less than about 10 μM, less than about 5 μM, less than about 4 μM, less than about 3 μM, less than about 2 μM, less than about 1 μM, less than about 900 nM, less than about 800 nM, less than about 700 nM, less than about 600 nM, less than about 500 nM, less than about 400 nM, less than about 300 nM, less than about 200 nM, less than about 100 nM, less than about 90 nM, less than about 80 nM, less than about 70 nM, less than about 60 nM, less than about 50 nM, less than about 40 nM, less than about 30 nM, less than about 20 nM, less than about 10 nM, less than about 5 nM, less than about 1 nM, less than about 500 pM, or less than about 100 pM. Modifications for reduced expression of endogenous TCR genes The host cell can further comprise one or more modifications (e.g., genomic mutation(s)) that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus. Decreased expression of TRAC, TRBC1, and / or TRBC2 can, for example, reduce mispairing of transgenic TCR chains that are introduced into a host cell (e.g., anti-p53 R175H TCRs disclosed herein) with endogenous TCR chains, improve functional expression of the transgenic TCRs, and improve TCR complex signaling and functionality by freeing the available pool of CD3 proteins to bind to the transgenic TCR rather than endogenous TCR chains. In some embodiments, the modification can facilitate enhanced in vitro, ex vivo, or in vivo tumor cell killing by engineered immune cells relative to control cells lacking the modification. In some embodiments, the modification can facilitate enhanced sensitivity to a given (e.g., low) density of a target antigen (e.g., p53 R175H mutant peptide) compared to a corresponding control cell lacking the modification. In some embodiments, the genomic mutation that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus comprises an indel in the TRAC, TRBC1, or TRBC2 locus. In some embodiments, the genomic mutation that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus is a missense mutation and may result in reduced function or stability of a T cell receptor α or T cell receptor β polypeptide encoded in the genome of the host cell. In some embodiments, the genomic mutation that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus also results in premature termination of a T cell receptor α or T cell receptor β polypeptide translated from a genomic mRNA of the cell. In some cases, the host cell comprises genomic mutations that cause or contribute to decreased expression of both (i) TRAC; and (ii) TRBC1 or TRBC2. In some cases, the host cell comprises a genomic mutation that causes or contributes to decreased expression of TRAC, TRBC1, and TRBC2. The genomic mutation can be or can comprise an insertion, e.g., of an expression cassette. The genomic mutation can be or can comprise a deletion. The genomic mutation can be or can comprise a substitution. In some embodiments, the genomic mutation that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus comprises an insertion of a heterologous polynucleotide of the present disclosure (e.g., a polynucleotide comprising a nucleic acid sequence encoding a binding protein capable of binding a p53 R175H mutant peptide, or a heterologous polynucleotide encoding a binding protein of the present disclosure) at the endogenous TRAC, TRBC1, or TRBC2 locus. In some embodiments, the host cell is further modified to decrease and / or knock out expression of endogenous TRAC, TRBC1, and / or TRBC2. Accordingly, in some embodiments, the expression of each of endogenous TRAC, TRBC1, and TRBC2 is decreased and / or knocked out. In some embodiments, the modification comprises deletion of, for example, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% of the open reading frame of endogenous TRAC, TRBC1, or TRBC2. In some embodiments, the modification comprises knockdown of expression of the TRAC, TRBC1, or TRBC2, for example, using a shRNA or siRNA. In some embodiments, the modification comprises a genomic disruption. In some embodiments, the modification comprises insertion of, for example, a transposon, or a premature stop codon. In some embodiments, expression of endogenous TRAC, TRBC1, and / or TRBC2 is reduced by at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9-fold, at least 10-fold, at least 11-fold, at least 12-fold, at least 13-fold, at least 14-fold, at least 15-fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 60-fold, at least 70-fold, at least 80-fold, at least 90-fold, at least 100-fold, at least 150-fold, at least 200-fold, at least 250-fold, at least 300- fold, at least 350-fold, at least 400-fold, at least 500-fold, at least 600-fold, at least 700-fold, at least 800-fold, at least 900-fold, at least 1000-fold, or at least 5000-fold. In some embodiments, expression of TRAC, TRBC1, and / or TRBC2 is eliminated or substantially eliminated. In some embodiments, expression of TRAC, TRBC1, and / or TRBC2 is reduced to below a limit of detection. The reduced expression of TRAC, TRBC1, and / or TRBC2 can be determined, for example, by a flow cytometric assay (e.g., for proportion of positive cells or mean fluorescence intensity, in a population of interest). In some embodiments, the reduction in expression of endogenous TRAC, TRBC1, and / or TRBC2 is found in at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 95%, at least 97%, or at least 99% of host cells in a population. In some cases, the reduction of expression is found by a genomic sequencing method. In some embodiments, a population of host cells disclosed herein comprising one or more modifications (e.g., genomic mutation(s)) that result in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2 exhibits at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9- fold, at least 10-fold, at least 11-fold, at least 12-fold, at least 13-fold, at least 14-fold, at least 15- fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 60-fold, at least 70- fold, at least 80-fold, at least 90-fold, at least 100-fold, at least 150-fold, at least 200-fold, at least 250-fold, at least 300-fold, at least 350-fold, at least 400-fold, at least 500-fold, at least 600-fold, at least 700-fold, at least 800-fold, at least 900-fold, at least 1000-fold, or at least 5000-fold increased killing of target cells as compared to a population of control cells (for example, cells without reduced expression of TRAC, TRBC1, and / or TRBC2). The killing of target cells can be, for example, as determined by an in vitro cytotoxicity assay. The host cells can comprise a binding protein (e.g., a TCR comprising Vα and Vβ regions and / or CDRs disclosed herein) that binds a target antigen (for example, a p53 mutant peptide, such as p53 R175H mutant peptide, e.g., present in a peptide:HLA complex). In some embodiments, a population of host cells disclosed herein comprising one or more modifications (e.g., genomic mutation(s)) that result in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2 exhibits at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9- fold, at least 10-fold, at least 11-fold, at least 12-fold, at least 13-fold, at least 14-fold, at least 15- fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 60-fold, at least 70- fold, at least 80-fold, at least 90-fold, at least 100-fold, at least 150-fold, at least 200-fold, at least 250-fold, at least 300-fold, at least 350-fold, at least 400-fold, at least 500-fold, at least 600-fold, at least 700-fold, at least 800-fold, at least 900-fold, at least 1000-fold, or at least 5000-fold increased activation in response to target cells as compared to a population of control cells (for example, cells without reduced expression of TRAC, TRBC1, and / or TRBC2). The host cells can comprise a binding protein (e.g., a TCR comprising Vα and Vβ regions and / or CDRs disclosed herein) that binds a target antigen (for example, a p53 R175H mutant peptide, e.g., present in a peptide:HLA complex). The activation can be, for example, as determined by an assay for determining expression an activation marker (e.g., CD137, CD69, Granzyme B, CD107a, IFN-gamma, TNF-a, IL-12, a cytokine, an interleukin, an interferon) upon exposure to target cells that express or present the target antigen. In some embodiments, a population of host cells disclosed herein comprising one or more modifications (e.g., genomic mutation(s)) that result in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2 exhibits at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 6-fold, at least 7-fold, at least 8-fold, at least 9- fold, at least 10-fold, at least 11-fold, at least 12-fold, at least 13-fold, at least 14-fold, at least 15- fold, at least 20-fold, at least 30-fold, at least 40-fold, at least 50-fold, at least 60-fold, at least 70- fold, at least 80-fold, at least 90-fold, at least 100-fold, at least 150-fold, at least 200-fold, at least 250-fold, at least 300-fold, at least 350-fold, at least 400-fold, at least 500-fold, at least 600-fold, at least 700-fold, at least 800-fold, at least 900-fold, at least 1000-fold, or at least 5000-fold increased avidity for a target antigen of a binding protein as compared to a population of control cells (for example, cells without reduced expression of TRAC, TRBC1, and / or TRBC2). The host cells can comprise a binding protein (e.g., a TCR comprising Vα and Vβ regions and / or CDRs disclosed herein) that binds a target antigen (for example, a p53 mutant peptide, such as p53 R175H mutant peptide, e.g., present in a peptide:HLA complex). The increase in avidity can be, for example, as determined by an assay for determining expression an activation marker (e.g., CD137, CD69, Granzyme B, CD107a, IFN-gamma, TNF-a, IL-12, a cytokine, an interleukin, an interferon) upon exposure to target cells that express or present the target antigen, or and / or an assay to determine EC50(e.g., peptide dose at which a half-maximal activation of a T cell population is reached). In some embodiments, a population of host cells disclosed herein comprising one or more modifications (e.g., genomic mutation(s)) that result in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2 exhibits at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold, at least 20-fold, or at least 50-fold increased binding to a target antigen of a binding protein as compared to a population of control cells (for example, cells without reduced expression of TRAC, TRBC1, and / or TRBC2). The host cells can comprise a binding protein (e.g., a TCR comprising Vα and Vβ regions and / or CDRs disclosed herein) that binds the target antigen (for example, a p53 mutant peptide, such as p53 R175H mutant peptide, e.g., present in a peptide:HLA complex). The increase in binding can be, for example, as determined by an assay comprising staining with peptide-HLA multimers (e.g., tetramers or pentamers). In some embodiments, a population of host cells disclosed herein comprising one or more modifications (e.g., genomic mutation(s)) that result in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2 exhibits at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold, at least 20-fold, at least 50-fold, at least 100-fold, or at least 500-fold increased expression (e.g., cell surface expression) of a binding protein as compared to a population of control cells (for example, cells without reduced expression of TRAC, TRBC1, and / or TRBC2). The binding protein can be a TCR comprising an alpha chain and beta chain (e.g., with Vα and Vβ regions and / or CDRs disclosed herein) that binds the target antigen (for example, a p53 mutant peptide, such as p53 R175H mutant peptide, e.g., present in a peptide:HLA complex). The increase in expression can be, for example, as determined by an assay comprising staining with peptide-HLA multimers (e.g., tetramers or pentamers) specific for the binding protein. In some embodiments, the population of host cells comprises decreased expression of endogenous TRAC relative to the control cells. In some embodiments, the population of host cells comprises decreased expression of endogenous TRBC1 relative to the control cells. In some embodiments, the population of host cells comprises decreased expression of endogenous TRBC2 relative to the control cells. In some embodiments, the population of host cells comprises decreased expression of endogenous TRAC and TRBC1 relative to the control cells. In some embodiments, the population of host cells comprises decreased expression of endogenous TRAC and TRBC2 relative to the control cells. In some embodiments, the population of host cells comprises decreased expression of endogenous TRBC1 and TRBC2 relative to the control cells. In some embodiments, the population of host cells comprises decreased expression of endogenous TRAC, TRBC1, and TRBC2 relative to the control cells. Additional polypeptides A host cell can be engineered to comprise further modifications in addition to a binding protein and a modification that causes or contributes to decreased expression of TRAC, TRBC1, and / or TRBC2. Three signals are commonly required for optimal T-cell activation and expansion: T-cell receptor (TCR) activation (“Signal 1”); co-stimulation (“Signal 2”); and cytokine stimulation (“Signal 3”). A host cell can comprise a transgenic polynucleotide encoding a polypeptide that comprises a CD8 co-receptor α (CD8α) chain or an extracellular portion thereof, and / or a transgenic polynucleotide encoding a CD8 co-receptor β (CD8β) chain polypeptide or an extracellular portion thereof. CD8 co-receptor can, for example, augment Signal 1 after a TCR binds its target. A host cell can be engineered to express a CD8 co-receptor disclosed herein, e.g., a CD8α chain and / or a CD8β chain. Illustrative, non-limiting examples of CD8α and CD8β amino acid sequences that can be used include those provided below, and variants thereof. An exemplary CD8 co-receptor α (CD8α) amino acid sequence is: MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFLLYLSQNK PKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIAS QPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLS ARYV (SEQ ID NO: 261) An exemplary CD8 co-receptor β (CD8β) amino acid sequence is: MALPVTALLLPLALLLHAARPSQFRVSPLDRTWNLGETVELKCQVLLSNPTSGCSWLFQPRGAAASPTFLLYLSQNK PKAAEGLDTQRFSGKRLGDTFVLTLSDFRRENEGYYFCSALSNSIMYFSHFVPVFLPAKPTTTPAPRPPTPAPTIAS QPLSLRPEACRPAAGGAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCNHRNRRRVCKCPRPVVKSGDKPSLS ARYV (SEQ ID NO: 262) A host cell can comprise a transgenic polynucleotide encoding a Fas-BB fusion protein. Illustrative, non-limiting examples of a FasBB fusion protein amino acid sequences that can be used include the sequences provided below, and variants thereof. In some embodiments, a FasBB fusion protein having a transmembrane domain derived from a Fas polypeptide has at least about 85% sequence identity to the following exemplary sequence: MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPGERKARDCTVNG DEPDCVPCQEGKEYTDKAHFSSKCRRCRLCDEGHGLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGII KECTLTSNTKCKEEGSRSNLGWLCLLLLPIPLIVWVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCE L (SEQ ID NO: 263) In some embodiments, a FasBB fusion protein having a transmembrane domain derived from a 4-1BB polypeptide has at least about 85% sequence identity to the following exemplary sequence: MLGIWTLLPLVLTSVARLSSKSVNAQVTDINSKGLELRKTVTTVETQNLEGLHHDGQFCHKPCPPGERKARDCTVNG DEPDCVPCQEGKEYTDKAHFSSKCRRCRLCDEGHGLEVEINCTRTQNTKCRCKPNFFCNSTVCEHCDPCTKCEHGII KECTLTSNTKCKEEGSRSNIISFFLALTSTALLFLLFFLTLRFSVVKRGRKKLLYIFKQPFMRPVQTTQEEDGCSCR FPEEEEGGCEL (SEQ ID NO: 264) An exemplary polynucleotide encoding a FasBB fusion protein comprising a Fas-derived transmembrane domain is provided below: ATGCTCGGCATCTGGACCCTGCTGCCTCTTGTGCTGACATCTGTGGCCAGGCTGTCCTCCAAGTCCGTGA ATGCCCAAGTGACCGACATCAACAGCAAAGGCCTGGAACTGAGAAAGACCGTGACCACCGTGGAAACCCA GAATCTGGAAGGCCTGCACCACGACGGCCAGTTCTGTCACAAACCATGTCCTCCAGGCGAGCGGAAGGCC AGAGATTGCACAGTGAATGGCGACGAGCCTGACTGCGTGCCCTGTCAAGAGGGCAAAGAGTACACCGACA AGGCCCACTTCAGCTCCAAGTGCCGCAGATGCAGACTGTGCGACGAAGGCCACGGACTGGAAGTGGAAAT CAACTGCACCCGGACACAGAACACCAAGTGCAGATGCAAGCCCAACTTCTTCTGCAACTCCACCGTGTGC GAGCACTGCGACCCTTGTACCAAGTGCGAGCATGGCATCATCAAAGAGTGCACCCTGACCTCCAACACGA AGTGCAAAGAGGAAGGCAGCAGAAGCAACCTCGGCTGGCTCTGTTTGCTGCTGCTCCCCATTCCTCTGAT CGTGTGGGTCAAGAGAGGCCGGAAGAAGCTGCTGTACATCTTCAAGCAGCCCTTCATGCGGCCCGTGCAG ACCACACAAGAGGAAGATGGCTGCTCCTGCAGATTCCCTGAGGAAGAAGAAGGCGGCTGCGAACTC (SEQ ID NO: 388) An exemplary polynucleotide encoding a FasBB fusion protein comprising a 4-1BB- derived transmembrane domain is provided below: CACCATGCTGGGCATCTGGACCCTGCTGCCTCTGGTGCTGACAAGCGTGGCCAGACTGAGCAGCAAGAGC GTGAACGCCCAAGTGACCGACATCAACAGCAAGGGCCTGGAACTGAGAAAGACCGTGACCACCGTGGAAA CCCAGAACCTGGAAGGCCTGCACCACGACGGCCAGTTCTGCCACAAGCCTTGTCCCCCTGGCGAGCGGAA GGCCAGAGACTGTACTGTGAACGGCGACGAGCCCGACTGCGTGCCCTGTCAGGAAGGCAAAGAGTACACC GACAAGGCCCACTTCAGCAGCAAGTGCCGGCGGTGCAGACTGTGTGATGAGGGCCACGGCCTGGAAGTGG AAATCAACTGCACCCGGACCCAGAACACCAAGTGCAGATGCAAGCCCAACTTCTTCTGCAACAGCACCGT GTGCGAGCACTGCGACCCCTGTACCAAGTGCGAACACGGCATCATCAAAGAGTGCACCCTGACCTCCAAC ACAAAGTGCAAAGAGGAAGGCAGCAGAAGCAACATCATATCCTTCTTCCTGGCGTTGACCTCTACCGCGC TGCTTTTCTTGCTGTTCTTCCTTACGCTCCGCTTCAGTGTGGTTAAGCGGGGCAGAAAGAAGCTGCTGTA CATCTTCAAGCAGCCTTTCATGCGGCCCGTGCAGACCACCCAGGAAGAGGACGGCTGCTCCTGCAGATTC CCCGAGGAAGAAGAAGGCGGCTGCGAGCTG The FasBB switch receptor (also referred to as Fas-41BB, Fas-4-1BB, or FASBB) can comprise, for example, an extracellular domain of Fas or a FasL-binding fragment thereof, and an intracellular signaling domain of 41BB or a signaling domain thereof. A FasBB fusion protein can be useful for, for example, converting a signal initiated by the binding of Fas to its target (e.g., FasL) into a positive (e.g., costimulatory) signal generated by the 41BB intracellular signaling domain, thereby improving anti-cancer immune functionality of a host cell disclosed herein (e.g., increased proliferation, survival in the tumor microenvironment, and increased cytotoxic function, cytokine production, and metabolism to support T cell activation and memory development). Accordingly, FasBB fusion proteins disclosed herein can, for example, provide a co-stimulatory signal (“Signal 2”) required for T-cell activation and expansion. The extracellular component can comprise all or a portion of the extracellular domain of Fas or can be truncated to maintain a short spatial distance between the host cell and an interaction partner (e.g., ~9 amino acids (aas)) upon receptor-ligand interaction. The FasBB fusion protein can comprise a transmembrane domain, for example, a Fas, 4-1BB, or CD28 transmembrane domain. FasBB fusion proteins are described in more detail in, for example, U.S. Patent No.11,725,210 B2, the entire contents of which are hereby incorporated by reference. A host cell can comprise a transgenic polynucleotide encoding a chimeric fusion protein that comprises an interleukin-7 receptor intracellular signaling domain. The chimeric fusion protein can comprise, for example, an intracellular portion of an Interleukin 7 Receptor A (IL7RA) polypeptide, or a portion or variant thereof that is capable of contributing to an IL-7 signal in a host cell. A chimeric IL7R fusion protein can, for example, provide a "Signal 3" to increase STAT5 phosphorylation and host cell functionality, enhance proliferation of a host cell, increase host cell survival (e.g., in the tumor microenvironment), and / or enhance chemokine receptor expression. Interleukin-7 receptor subunit alpha can also be referred to as ILR, IL7R-α, as IL7RA, as IL-7R-alpha, as ILRA, as Interleukin-7 receptor-α, as interleukin 7 receptor, as Cluster of Differentiation 127 as CD127, or as CDW127. In some embodiments, the ILR comprises a mutation that enables or facilitates homodimerization of the receptor. In some embodiments, the chimeric fusion protein comprises a transmembrane domain of IL7R, IL2RA, IL2RB, IL2RG, IL14R, IL15R, IL9R, IL21R, CD2, CD40L, CD58, CD80, TGFβR2, or SIRPα. In some embodiments, the chimeric fusion protein comprises an extracellular component comprising: (i) an extracellular domain of a Cluster of Differentiation 80 (CD80) polypeptide, or a portion or variant thereof that is capable of binding a CD28 or CTLA-4 polypeptide; (ii) an extracellular domain of a Cluster of Differentiation 58 (CD58) polypeptide, or a portion or variant thereof that is capable of binding a Cluster of Differentiation 2 (CD2) polypeptide; (iii) an extracellular domain of a Signal Regulatory Protein Alpha (SIRPα) polypeptide, or a portion or variant thereof that is capable of binding a Cluster of Differentiation 47 (CD47) polypeptide; (iv) an extracellular domain of a Cluster of Differentiation 40L (CD40L) polypeptide, or a portion or variant thereof that is capable of binding a CD40 polypeptide; (v) an extracellular domain of a Cluster of Differentiation 2 (CD2) receptor, or a portion or variant thereof that is capable of binding a CD58 polypeptide; (vi) an extracellular domain of a Cluster of Differentiation 34 (CD34) polypeptide; or (vii) an extracellular domain of a TGFβR2 polypeptide. In some embodiments, the fusion protein comprises an amino acid sequence listed in Table 3. Table 3: Exemplary Fusion Proteins and components thereof

[0002] In the Table above, EC denotes an extracellular domain, TM denotes a transmembrane domain, and IC denotes an intracellular domain. In the Table above, inserted sequences are bolded alone. For SEQ ID NOs.291-384, wild-type sequences are bolded and underlined, inserted sequences are bolded alone, and sequences that are neither bolded nor underlined denote juxtamembrane sequences. In some embodiments, a population of host cells comprising one or more modifications disclosed herein (e.g., expression of a FasBB fusion protein and / or chimeric ILR polypeptide disclosed herein) exhibits at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold, at least 50-fold, or at least 100-fold, at least 500-fold, or at least 1000-fold increased proliferation in response to target cells (e.g., that present a p53 R175H peptide) as compared to a population of control cells (for example, corresponding cells lacking the FasBB fusion protein and / or chimeric ILR polypeptide). The proliferation can be, for example, as determined by an in vitro lymphoproliferation assay or measurement of host cell number after co-incubation. The host cells can comprise a binding protein (e.g., a TCR comprising Vα and Vβ regions and / or CDRs disclosed herein), and / or a modification that results in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2. In some embodiments, a population of host cells comprising one or more modifications disclosed herein (e.g., expression of a FasBB fusion protein and / or chimeric IL7R polypeptide disclosed herein) exhibits at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, at least 90%, at least 2-fold, at least 3-fold, at least 4-fold, at least 5-fold, at least 10-fold, at least 50-fold, or at least 100-fold, at least 500-fold, or at least 1000-fold increased killing of target cells as compared to a population of control cells (for example, corresponding cells lacking the FasBB fusion protein and / or chimeric ILR polypeptide). The killing of target cells can be, for example, as determined by an in vitro cytotoxicity assay. The host cells can comprise a binding protein (e.g., a TCR comprising Vα and Vβ regions and / or CDRs disclosed herein), and / or a modification that results in decreased expression of endogenous TRAC, TRBC1, and / or TRBC2. A nucleic acid encoding a polypeptide or polypeptides disclosed herein (e.g., binding protein, CD8 co-receptor chain or an extracellular portion thereof, FasBB fusion protein, and / or chimeric IL7 fusion protein) can encode a signal peptide. In some cases, a polypeptide of the disclosure comprises a signal peptide. A signal peptide can be cleaved off during processing of the polypeptide, thus in some cases a mature polypeptide disclosed herein does not contain a signal peptide. A signal peptide at the N-terminus of a protein can be involved in transport of the protein to or through a membrane, transport to different a membranous cellular compartment, or secretion of the protein from the cell. A nucleic acid encoding a protein of the disclosure can encode a signal peptide to facilitate membrane insertion and surface localization of the protein. A signal peptide can be selected for its ability to facilitate ER processing and cell surface localization of the protein. Any suitable signal peptide can be used. In some cases, the signal peptide can comprise a G-CSF signal peptide or a CD8α signal peptide. A signal peptide can be about 10 to about 40 amino acids in length. In some cases, a signal peptide is at least about 10, 15, 16, 20, 21, 22, 25, or 30 amino acids in length, or more. In some cases, a signal peptide is at most about 15, 16, 20, 21, 22, 25, or 30 amino acids in length, or less. In some cases, a signal peptide is about 16-30 amino acids in length. Compositions In some cases, the present disclosure provides for a pharmaceutically acceptable composition comprising a plurality of host cells described herein and a pharmaceutically acceptable carrier, excipient, or diluent. In some cases, the composition comprises a CD4+ T cell population and / or a CD8+ T cell population bearing: (i) the binding protein; and (ii) one or more genomic mutations that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, a T cell receptor β constant 2 (TRBC2) locus, or a combination thereof. In some embodiments, the composition comprises a CD4+ cell population comprising (i) at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% modified CD4+ T cells. In some embodiments, the composition comprises a CD8+ cell population comprising (ii) at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% modified CD8+ T cells. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co- receptor α (CD8α) chain or a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor β (CD8β) chain. In some embodiments, the CD4+ and / or CD8+ cells express a CD8 co-receptor disclosed herein, e.g., a CD8α chain and / or a CD8β chain. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a Fas-BB fusion protein / switch receptor disclosed herein. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a chimeric fusion protein that comprises an interleukin-7 receptor intracellular signaling domain disclosed herein. In some cases, the composition comprises both CD4+ and CD8+ cells bearing: (i) the binding protein and (ii) a genomic mutation that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus. In some cases, the composition comprises both of (ii) a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor α (CD8α) chain or a polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor β (CD8β) chain. In some cases, the composition comprises both CD4+ and CD8+ cells bearing: (i) the binding protein; and either or both of (ii) a genomic mutation that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor α (CD8α) chain or a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor β (CD8β) chain. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor α (CD8α) chain and a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor β (CD8β) chain. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a Fas-BB fusion protein / switch receptor disclosed herein. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a chimeric fusion protein that comprises an interleukin-7 receptor intracellular signaling domain disclosed herein. In some embodiments, the CD4+ and / or CD8+ cells further comprise a transgenic polynucleotide encoding a Fas-BB fusion protein / switch receptor disclosed herein and a transgenic polynucleotide encoding a chimeric fusion protein that comprises an interleukin-7 receptor intracellular signaling domain disclosed herein. In some embodiments, the CD4+ and / or CD8+ cells further comprise each of: a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor α (CD8α) chain; a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor β (CD8β) chain; a transgenic polynucleotide encoding a Fas-BB fusion protein / switch receptor disclosed herein; and a transgenic polynucleotide encoding a chimeric fusion protein that comprises an interleukin-7 receptor intracellular signaling domain disclosed herein. In some embodiments, the composition comprises a CD4+ cell population comprising (i) at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% modified CD4+ T cells. In some embodiments, the composition further comprises a CD8+ cell population comprising (ii) at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% modified CD8+ T cells. In some cases, the composition comprises a reduced amount or substantially no naïve T cells. In some embodiments, the composition comprises about a 1:1 ratio of CD4+ to CD8+ T cells. In some cases, the composition comprises both CD4+ and CD8+ cells bearing: (i) the binding protein; and either or both of (ii) a genomic mutation that causes or contributes to decreased expression of an endogenous T cell receptor α constant (TRAC), a T cell receptor β constant 1 (TRBC1) locus, or a T cell receptor β constant 2 (TRBC2) locus. In some embodiments, the CD4+ or CD8+ cells further comprise a transgenic polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor α (CD8α) chain or a resulting polynucleotide encoding a polypeptide that comprises an extracellular portion of a CD8 co-receptor β (CD8β) chain. In some embodiments, the composition comprises a CD4+ cell population comprising (i) at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% modified CD4+ T cells. In some embodiments, the composition further comprises a CD8+ cell population comprising at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 85%, at least about 90%, or at least about 95% modified CD8+ T cells. In some cases, the composition comprises a reduced amount or substantially no naïve T cells. In some embodiments, the composition comprises about a 1:1 ratio, about a 1:2 ratio, about a 1:3 ratio, about a 1:4 ratio, about a 1:5 ratio, about a 1:6 ratio, about a 1:7 ratio, about a 1:8 ratio, about a 1:9 ratio, about a 1:10 ratio, about a 2:1 ratio, about a 3:1 ratio, about a 4:1 ratio, about a 5:1 ratio, about a 6:1 ratio, about a 7:1 ratio, about an 8:1 ratio, about a 9:1 ratio, or about a 10:1 ratio of CD4+ to CD8+ T cells. In some cases, the carrier or excipient comprises albumin. In some cases, the diluent comprises physiologically normal saline. Suitable excipients can also include water, saline, dextrose, glycerol, or the like, and combinations thereof. In some embodiments, a composition comprises a suitable infusion media. Suitable infusion media can be any isotonic medium formulation, normal saline, Normosol R (Abbott) or Plasma-Lyte A (Baxter), 5% dextrose in water, or Ringer's lactate can be utilized. An infusion medium can be supplemented with human serum albumin or other human serum components. Polynucleotides and Vectors In some aspects, the present disclosure provides for a polynucleotide comprising an open reading frame encoding a binding protein (e.g., a binding protein capable of binding a p53 mutant peptide). The open reading frame can be operatively linked to a promoter (e.g., heterogenous promoter). The binding protein can comprise a TCR α chain variable (Vα) domain; a TCR β chain variable (Vβ) domain; a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region; or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region disclosed herein, for example, comprising a sequence having at least about 84%, at least about 85%, at least about 86%, at least about 87%, at least about 88%, at least about 89%, at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or 100% identity to any of the sequences described herein. The polynucleotide can be codon optimized. In some cases, the heterogenous promoter is not a mammalian promoter. In some cases, the heterogenous promoter is a constitutive promoter that is not a TCR promoter. In some cases, the heterogenous promoter is a viral promoter. In some cases, the heterogenous promoter is a mammalian promoter. In some cases, the heterogenous promoter is a human promoter. In some cases, the heterogenous promoter is a synthetic promoter. In some cases, the heterogenous promoter is an inducible promoter. In some cases, the heterogenous promoter is a tissue-specific promoter. In some cases, the heterogenous promoter is an immune cell-specific promoter. In some embodiments, the promoter is a murine stem cell virus (MSCV) promoter. In some embodiments, the promoter has at least about 85% sequence identity to the following exemplary sequence: MSCV promoter AATGAAAGACCCCACCTGTAGGTTTGGCAAGCTAGCTTAAGTAACGCCATTTTGCAAGGCATGGAAAATACATAACT GAGAATAGAGAAGTTCAGATCAAGGTTAGGAACAGAGAGACAGCAGAATATGGGCCAAACAGGATATCTGTGGTAAG CAGTTCCTGCCCCGGCTCAGGGCCAAGAACAGATGGTCCCCAGATGCGGTCCCGCCCTCAGCAGTTTCTAGAGAACC ATCAGATGTTTCCAGGGTGCCCCAAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCT CGCTTCTGTTCGCGCGCTTCTGCTCCCCGAGCTCAATAAAAGAGCCCACAACCCCTCACTCGGCGCGCCAGTCCTCC GATAGACTGCGTCGCCCGGGTACCCGTATTCCCAATAAAGCCTCTTGCTGTTTGCATCCGAATCGTGGACTCGCTGA TCCTTGGGAGGGTCTCCTCAGATTGATTGACTGCCCACCTCGGGGGTCTTTCATTAAGCTGGCCAGCGGTCGTTTCG TGTCTGTCTCTGTCTTTGTGCGTGTTTGTGCCGGCATCTAATGTTTGCGCCTGCGTCTGTACTAGTTAGCTAACTAG CTCTGTATCTGGCGGACCCGTGGTGGAACTGACGAGTTCTGAACACCCGGCCGCAACCCTGGGAGACGTCCCAGGGA CTTTGGGGGCCGTTTTTGTGGCCCGACCTGAGGAAGGGAGTCGATGTGGAATCCGACCCCGTCAGGATATGTGGTTC TGGTAGGAGACGAGAACCTAAAACAGTTCCCGCCTCCGTCTGAATTTTTGCTTTCGGTTTGGAACCGAAGCCGCGCG TCTTGTCTGCTGCAGCGCTGCAGCATCGTTCTGTGTTGTCTCTGTCTGACTGTGTTTCTGTATTTGTCTGAAAATTA GGGCCAGACTGTTACCACTCCCTTAAGTTTGACCTTAGGTCACTGGAAAGATGTCGAGCGGATCGCTCACAACCAGT CGGTAGATGTCAAGAAGAGACGTTGGGTTACCTTCTGCTCTGCAGAATGGCCAACCTTTAACGTCGGATGGCCGCGA GACGGCACCTTTAACCGAGACCTCATCACCCAGGTTAAGATCAAGGTCTTTTCACCTGGCCCGCATGGACACCCAGA CCAGGTCCCCTACATCGTGACCTGGGAAGCCTTGGCTTTTGACCCCCCTCCCTGGGTCAAGCCCTTTGTACACCCTA AGCCTCCGCCTCCTCTTCCTCCATCCGCCCCGTCTCTCCCCCTTGAACCTCCTCGTTCGACCCCGCCTCGATCCTCC CTTTATCCAGCCCTCACTCCTTCTCTAGGCGCC In some embodiments, the polynucleotide is promoterless. In some embodiments, the promoterless polynucleotide is designed to be operatively linked to an endogenous promoter at the site of insertion. In some embodiments, the promoter is an elongation factor-1 alpha (EF-1α) promoter. In some embodiments, the promoter has at least about 85% sequence identity to the following exemplary sequence: EF-1α promoter GGCTCCGGTGCCCGTCAGTGGGCAGAGCGCACATCGCCCACAGTCCCCGAGAAGTTGGGGGGAGGGGTCGGCAATTG AACCGGTGCCTAGAGAAGGTGGCGCGGGGTAAACTGGGAAAGTGATGTCGTGTACTGGCTCCGCCTTTTTCCCGAGG GTGGGGGAGAACCGTATATAAGTGCAGTAGTCGCCGTGAACGTTCTTTTTCGCAACGGGTTTGCCGCCAGAACACAG GTAAGTGCCGTGTGTGGTTCCCGCGGGCCTGGCCTCTTTACGGGTTATGGCCCTTGCGTGCCTTGAATTACTTCCAC TGGCTGCAGTACGTGATTCTTGATCCCGAGCTTCGGGTTGGAAGTGGGTGGGAGAGTTCGAGGCCTTGCGCTTAAGG AGCCCCTTCGCCTCGTGCTTGAGTTGAGGCCTGGCCTGGGCGCTGGGGCCGCCGCGTGCGAATCTGGTGGCACCTTC GCGCCTGTCTCGCTGCTTTCGATAAGTCTCTAGCCATTTAAAATTTTTGATGACCTGCTGCGACGCTTTTTTTCTGG CAAGATAGTCTTGTAAATGCGGGCCAAGATCTGCACACTGGTATTTCGGTTTTTGGGGCCGCGGGCGGCGACGGGGC CCGTGCGTCCCAGCGCACATGTTCGGCGAGGCGGGGCCTGCGAGCGCGGCCACCGAGAATCGGACGGGGGTAGTCTC AAGCTGGCCGGCCTGCTCTGGTGCCTGGCCTCGCGCCGCCGTGTATCGCCCCGCCCTGGGCGGCAAGGCTGGCCCGG TCGGCACCAGTTGCGTGAGCGGAAAGATGGCCGCTTCCCGGCCCTGCTGCAGGGAGCTCAAAATGGAGGACGCGGCG CTCGGGAGAGCGGGCGGGTGAGTCACCCACACAAAGGAAAAGGGCCTTTCCGTCCTCAGCCGTCGCTTCATGTGACT CCACGGAGTACCGGGCGCCGTCCAGGCACCTCGATTAGTTCTCGAGCTTTTGGAGTACGTCGTCTTTAGGTTGGGGG GAGGGGTTTTATGCGATGGAGTTTCCCCACACTGAGTGGGTGGAGACTGAAGTTAGGCCAGCTTGGCACTTGATGTA ATTCT0CCTTGGAATTTGCCCTTTTTGAGTTTGGATCTTGGTTCATTCTCAAGCCTCAGACAGTGGTTCAAAGTTTT TTTCTTCCATTTCAGGTGTCGTGA In some embodiments, the promoter is a Meiotic Nuclear Divisions 1 (MND1) promoter. In some embodiments, the promoter has at least about 85% sequence identity to the following exemplary sequence: TTTTATCGATCACGAGACTAGCCTCGAGAAGCTTGATGGCCGCCAGTGTGATGGATATCTGCAGAATTCGCCCTTAT GGGGATCCGAACAGAGAGACAGCAGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGG GCCAAGAACAGTTGGAACAGCAGAATATGGGCCAAACAGGATATCTGTGGTAAGCAGTTCCTGCCCCGGCTCAGGGC CAAGAACAGATGGTCCCCAGATGCGGTCCCGCCCTCAGCAGTTTCTAGAGAACCATCAGATGTTTCCAGGGTGCCCC AAGGACCTGAAATGACCCTGTGCCTTATTTGAACTAACCAATCAGTTCGCTTCTCGCTTCTGTTCGCGCGCTTCTGC TCCCCGAGCTCTATATAAGCAGAGCTCGTTTAGTGAACCGTCAGATCGCCTGGAGACGCCATCCACGCTGTTTTGAC CTCCATAGAAGACACCGACTCTAGAGGATCCACCGGTC In some embodiments, the nucleic acid encodes a binding protein capable of binding to a peptide:HLA complex, wherein the peptide comprises p53 R175H mutant peptide. In some embodiments, the binding protein is human, humanized, or chimeric. In some embodiments, the binding protein is selective for the p53 R175H mutant peptide. In some embodiments, the binding protein has a log10EC50for the p53 R175H mutant peptide of about -6.0 or less, about - 6.1 or less, about -6.2 or less, about -6.3 or less, about -6.4 or less, about -6.5 or less, about -6.6 or less, about -6.7 or less, about -6.8 or less, about -6.9 or less, about -7.0 or less, about -7.1 or less, about -7.2 or less, about -7.3 or less, about -7.4 or less, about -7.5 or less, about -7.6 or less, about -7.7 or less, about -7.8 or less, about -7.9 or less, about -8.0 or less, about -8.1 or less, about -8.2 or less, about -8.3 or less, about -8.4 or less, about -8.5 or less, about -8.6 or less, about -8.7 or less, about -8.8 or less, about -8.9 or less, about -9 or less, about -9.1 or less, or about -9.2 or less. In some aspects, the present disclosure provides for a vector comprising any of the polynucleotides described herein. In some cases, the vector is a viral vector, such as a lentiviral vector, a γ-retroviral vector, or an adeno-associated virus (AAV) vector. In some embodiments, the vector is a non-viral vector, for example, a plasmid, nanoplasmid, minicircle, a midge, a MIP, or a doggybone, a lipid-based nanoparticle, a liposome, a circular polynucleotide (e.g., DNA or RNA), a linear polynucleotide (e.g., a DNA or RNA), or a combination thereof. Methods of Treatment In some aspects, the present disclosure provides for a method of treating a disease or disorder associated with a p53 R175H mutation in a subject, comprising administering to the subject an effective amount of any of the host cells or compositions described herein. In some embodiments, the host cell is autologous to the subject. In some embodiments, the host cell is allogenic to the subject. In some embodiments, the host cell is HLA-matched to the subject, for example, HLA matched at all typed HLA alleles. In some embodiments, a host cell and a subject can be HLA-typed HLA-A, HLA-B, HLA-C, and / or HLA-DR alleles. In some embodiments, the host cell and subject are matched for at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 HLA alleles. In some embodiments, the host cell is haploidentical to the subject. In some embodiments, the subject is positive for an HLA-A*02 allele. In some embodiments, the subject is positive for an HLA-A*02:01 allele. In some embodiments, the disease or disorder comprises a cancer. In some embodiments, the cancer is a solid cancer. In some embodiments, the cancer is a hematological malignancy. In some embodiments, the disease or disorder is selected from a pancreas cancer or carcinoma, optionally a pancreatic ductal adenocarcinoma (PDAC); a colorectal cancer or carcinoma; a lung cancer, optionally a non-small-cell lung carcinoma; a biliary cancer; an endometrial cancer or carcinoma; a cervical cancer; an ovarian cancer; a bladder cancer; a liver cancer; a myeloid leukemia, optionally myeloid leukemia such as acute myeloid leukemia; a myelodysplastic syndrome; a lymphoma such as Non-Hodgkin lymphoma; Chronic Myelomonocytic Leukemia; Acute Lymphoblastic Leukemia (ALL); a cancer of the urinary tract; a cancer of the small intestine; a breast cancer or carcinoma; a melanoma (optionally a cutaneous melanoma, an anal melanoma, or a mucosal melanoma); a glioma; a poorly differentiated thyroid gland carcinoma; a neuroblastoma; a histiocytic and dendritic cell neoplasm; neurofibromatosis Type 1; rhabdomyosarcoma; a soft tissue sarcoma; a bladder carcinoma; a sarcoma; a glioblastoma; a squamous cell lung carcinoma; an anaplastic astrocytoma; chronic myeloid leukemia; diffuse large B-cell lymphoma; double-hit lymphoma; head and neck carcinoma; head and neck squamous cell carcinoma; hepatocellular carcinoma; malignant peripheral nerve sheath tumor; mantle cell lymphoma; myelodysplastic / myeloproliferative neoplasm, unclassifiable; peripheral T cell lymphoma; prostate carcinoma; refractory anemia with excess blasts-2; renal cell carcinoma; rhabdoid tumor; schwannoma; secondary AML; small cell lung carcinoma; therapy- related AML; thymic carcinoma; thyroid gland follicular carcinoma; malignant thyroid gland neoplasm; thyroid gland carcinoma; thyroid gland adenocarcinoma; urothelial carcinoma; or thyroid gland papillary carcinoma. In some embodiments, the method for treating a disease or disorder associated with a p53 R175H mutation in a subject further comprises genotyping a tumor of the subject for a p53 R175H allele prior to the administering. In some embodiments, the method further comprises genotyping the subject for an HLA-A allele prior to the administering. In some cases, the subject is determined to carry a p53 R175H allele prior to the administering. In some cases, the subject has been genotyped for an HLA-A*02 allele (e.g., HLA-A*02 or HLA-A*02:01) prior to the administering. An effective amount of a pharmaceutical composition (e.g., a population of host cells disclosed herein) can describe an amount sufficient, at dosages and for periods of time needed, to achieve the predetermined clinical results or beneficial result. An effective amount may be delivered in one or more administrations. If the administration is to a subject already known or confirmed to have a disease or disease-state, the term "therapeutic amount" may be used in reference to treatment, whereas "prophylactically effective amount" may be used to describe administrating an effective amount to a subject that is susceptible or at risk of developing a disease or disease-state (e.g., recurrence) as a preventative course. Administration may be affected continuously or intermittently, and parenterally. A composition can be administered locally (e.g., intratumorally) or systemically (e.g., intravenously). Administration may be for treating a subject already confirmed as having a recognized condition, disease or disease state, or for treating a subject susceptible to or at risk of developing such a condition, disease or disease state. Co-administration with an adjunctive therapy may include simultaneous or sequential delivery of multiple agents in any order and on any dosing schedule. Methods disclosed herein may further include administering one or more additional agents to treat the disease or disorder in a combination therapy. For example, in certain embodiments, a combination therapy comprises administering a host cell with (concurrently, simultaneously, or sequentially) an immune checkpoint inhibitor. In some embodiments, a combination therapy comprises administering a host cell with an agonist of a stimulatory immune checkpoint agent. In some embodiments, a combination therapy comprises administering a host cell with a secondary therapy, such as chemotherapeutic agent, a radiation therapy, a surgery, an antibody, or any combination thereof. Methods of Manufacturing In some aspects, the present disclosure provides for a method of manufacturing a host cell, comprising contacting to the host cell: (a) any of the polynucleotides or vectors described herein. In some cases, the method further comprises contacting to the host cell: (b) an endonuclease (e.g., Cas endonuclease, such as a class II, type V Cas endonuclease); and (c) a guide RNA compatible with the endonuclease (e.g., compatible with the class II, type V Cas endonuclease), wherein the guide RNA is configured to hybridize to a nucleic acid sequence in the cell's genome. In some embodiments, the guide RNA is configured to hybridize to an endogenous T cell receptor constant region locus of the host cell prior to the polynucleotide or vector or after the polynucleotide or vector. In some embodiments, the contacting comprises transfection or transduction. In some embodiments, the transfection comprises electroporation. In some embodiments, the T cell receptor constant region locus is a TRAC, TRBC1, or TRBC2 locus. In some embodiments, the host cell comprises an immune cell or a precursor thereof. In some embodiments, the immune cell comprises a T cell, a NK cell, a NK-T cell, a dendritic cell, a macrophage, a monocyte, or any combination thereof. In some embodiments, the immune cell comprises a T cell, wherein the T cell comprises a CD4+ T cell, a CD8+ T cell, a CD4- CD8- double negative T cell, a γδ T cell, or any combination thereof. Cells can be engineered to comprise or be capable of expressing a binding protein, an additional polypeptide disclosed herein, and / or to reduce expression of an endogenous TCR gene. For example, cell engineering techniques disclosed herein and / or known to a skilled person can be used to modify cells to comprise a recombinant nucleic acid that encodes a binding protein of the disclosure, and / or to introduce a modification to reduce expression of endogenous TRAC, TRBC1 and / or TRBC2, thereby generating host cells (such as engineered T cells). The methods can comprise contacting a cell with a recombinant nucleic acid, or with a vector that comprises the recombinant nucleic acid, under conditions that permit uptake of the recombinant nucleic acid by the cell. A recombinant nucleic acid can comprise a nucleotide sequence that encodes a binding protein disclosed herein or a component thereof. In some cases, a recombinant nucleic acid is utilized to alter the genome of a cell. A recombinant nucleic acid can be a polymer comprising or consisting essentially of nucleotides linked in a chain. Non-limiting examples of the recombinant nucleic include a circular nucleic acid, a DNA, a single stranded DNA, a double stranded DNA, a genomic DNA, a plasmid, a nanoplasmid, a plasmid DNA, a viral DNA, a minicircle (e.g., lacking a bacterial origin of replication), and an RNA. A recombinant nucleic acid can include one or more homology arms, for example, comprising sequences that are complementary to a genomic DNA sequence to be targeted for insertion (e.g., via homologous recombination). A recombinant nucleic acid can comprise one or more promoter regions, barcodes, restriction sites, cleavage sites, endonuclease recognition sites, primer binding sites, selectable markers, unique identification sequences, resistance genes, linker sequences (e.g., self-cleaving peptides such as P2A and / or T2A), or any combination thereof. In some aspects, these sites may be useful for enzymatic digestion, amplification, sequencing, targeted binding, purification, providing resistance properties (e.g., antibiotic resistance for selection), separating other encoded elements (e.g., binding proteins and fusion proteins) or any combination thereof. A recombinant nucleic acid may also include transcriptional or translational regulatory sequences, for example, one or more promoters, enhancers, insulators, internal ribosome entry sites, and / or polyadenylation signals. The homology arms can include additional modifications. In some embodiments, the homology arms may include sequence modifications designed to increase the efficiency of homology directed recombination (HDR). For example, sequence modifications to the homology arms may be included to disrupt a protospacer adjacent motif (PAM) site, such as by altering the sequence of the PAM site and / or a site proximal to the PAM site with a silent blocking mutation. Blocking mutations used to disrupt a PAM site are discussed in more detail, for example, in Okamoto et al., Scientific Reports 9, 4811 (2019), the entirety of which is hereby incorporated by reference. In some embodiments, the homology arms may be the same length, or different lengths. In some embodiments, the homology arms may each be between about 30 bp and about 2000 bp in length (e.g., 30, 50, 75, 100, 200, 250, 500, 750, 1000, 1250, 1500, 1750, 2000), about 100 and about 1500 bp in length, about 200 bp and about 700 bp in length, about 600 bp and about 1100 bp in length, about 400 bp and about 600 bp in length, about 700 and about 1000 bp in length, about 450 bp and about 550 bp in length, or about 800 and about 900 bp in length. Recombinant nucleic acids can be assembled by a variety of methods, e.g., by automated solid-phase synthesis. A recombinant nucleic acid can be constructed using standard solid-phase DNA / RNA synthesis. A recombinant nucleic acid can also be constructed using a synthetic procedure. A recombinant nucleic acid can be synthesized manually or in a fully automated fashion. In some cases, a synthetic procedure may comprise 5′-hydroxyl oligonucleotides that can be initially transformed into corresponding 5′-H-phosphonate mono esters, subsequently oxidized in the presence of imidazole to activated 5′-phosphorimidazolidates, and finally reacted with pyrophosphate on a solid support. This procedure may include a purification step after the synthesis such as PAGE, HPLC, MS, or any combination thereof. Recombinant nucleic acids can be purchased commercially. Recombinant nucleic acids described herein can be modified. In some cases, a recombinant nucleic acid can be modified to make it less immunogenic and more stable for transfection into a cell. For targeted integration, a recombinant nucleic acid sequence to be inserted can be flanked by homology arms comprising sequences that are complementary to a genomic DNA sequence to be targeted for insertion (e.g., via homologous recombination and / or homology- directed repair, HDR). A double stranded break can be introduced at a target site in the genome, and the homology arms can promote insertion of the recombinant nucleic acid. In some cases, a recombinant nucleic acid can be excised from a vector, such as a nanoplasmid (e.g., via a nuclease), and inserted into the genome of the cell. A recombinant nucleic acid can be inserted in a safe harbor locus. A safe harbor can comprise a genomic location where a recombinant nucleic acid can integrate and function without substantially perturbing endogenous activity, for example, with a relatively low impact on local or global gene expression. For example, one or more recombinant nucleic acids can be inserted into any one of HPRT, an AAVS site (E.G., AAVS1, AAVS2, etc.), CCR5, hROSA26, and / or any combination thereof. A recombinant nucleic acid can be inserted in an intergenic region. A recombinant nucleic acid can be inserted in a non-coding region. A recombinant nucleic acid can be inserted within a gene. In some cases, a recombinant nucleic acid can disrupt a gene it is inserted into (e.g., reduce or eliminate expression of the disrupted gene). A disrupted gene can be, for example, an endogenous TCR gene (e.g., TRAC, TCRB, TCRBC1, TRBC2, TRG, TRD), or an immune checkpoint gene (e.g., PD-1, CTLA-4). A recombinant nucleic acid can be inserted adjacent to or near to an endogenous promoter. Alternatively, a recombinant nucleic acid may comprise a promoter that is operably linked to the nucleic acid sequence intended to be expressed. A variety of enzymes can catalyze generation of a double-stranded break in the genome and / or insertion of foreign DNA into a host genome. Non-limiting examples of gene editing tools and techniques include CRISPR systems, CRISPR-associated polypeptide (Cas), TALEN, zinc finger nuclease (ZFN), zinc finger associate gene regulation polypeptide, meganuclease, Mega- TAL, transposon-based systems, natural master transcription factors, epigenetic modifying enzymes, recombinase, flippase, transposase, RNA-binding proteins (RBP), an Argonaute protein, any derivative thereof, any variant thereof, or any fragment thereof. A CRISPR system can be utilized to facilitate insertion of a recombinant nucleic acid encoding a binding protein or a component thereof into a cell genome. For example, a CRISPR system can introduce a double stranded break at a target site in a genome or a random site of a genome. In some cases, a CRISPR system comprises CRISPR-associated (Cas) proteins or Cas nucleases including type I CRISPR-associated (Cas) polypeptides, type II CRISPR-associated (Cas) polypeptides, type III CRISPR-associated (Cas) polypeptides, type IV CRISPR-associated (Cas) polypeptides, type V CRISPR-associated (Cas) polypeptides, or type VI CRISPR- associated (Cas) polypeptides a derivative, variant, or functional fragment thereof. In some embodiments, a CRISPR system comprises a Class I system or endonuclease (e.g., Type I, Type III or Type IV Cas proteins). A class I system can be of the I-A, I-B, I-C, I-U, I-D, I-E, I-F, IV-A, IV-B, III-A, III-D, III-C, or III-B subtype. In some embodiments, a CRISPR system comprises a Class II system or endonuclease (e.g., Type II, Type V, or Type VI). A class II, Type II system can be of the II-A, II-B, II-C1, or II-C2 subtype. A class II, Type V systems can of the V-A, V-B1, V-B2, V-C, V-D, V-E, V-F1, V-F1(V-U3), V-F2, V-F3, V-G, V-H, V-I, V-K (V-U5), V-U1, V-U2, or V-U4 subtype. A Class II, Type IV systems can be of the: VI-A, VI-B1, VI-B2, VI-C, or VI-D subtype. In some embodiments, a Cas protein used in a method disclosed herein is a class II endonuclease. In some embodiments, a Cas protein used in a method disclosed herein is a class II, type V Cas endonuclease. In some embodiments, a Cas protein used in a method disclosed herein is a class II, type V-A Cas endonuclease. Non-limiting examples of Cas proteins that can be used in the CRISPR systems include Cas1, Cas1B, Cas2, Cas3, Cas4, Cas5, Cas6, Cas7, Cas8, Cas9 (also known as Csn1 or Csx12), Cas10, Csy1, Csy2, Csy3, Cse1, Cse2, Csc1, Csc2, Csa5, Csn2, Csm2, Csm3, Csm4, Csm5, Csm6, Cmr1, Cmr3, Cmr4, Cmr5, Cmr6, Csb1, Csb2, Csb3, Csx17, Csx14, Csx10, Csx16, CsaX, Csx3, Csx1, Csx1S, Csf1, Csf2, CsO, Csf4, Cpf1, c2c1, c2c3, Cas9HiFi, MG29-1, homologues thereof, and modified versions thereof. An unmodified CRISPR enzyme can have DNA cleavage activity, such as Cas9. A CRISPR enzyme can direct cleavage of one or both strands at a target sequence, such as within a target sequence and / or within a complement of a target sequence. For example, a CRISPR enzyme can direct cleavage of one or both strands within or within about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 50, 100, 200, 500, or more base pairs from the first or last nucleotide of a target sequence. A Cas protein can be a high-fidelity Cas protein. Alternatives to S. pyogenes Cas9 may include RNA-guided endonucleases from the Cpf1 family that display cleavage activity in mammalian cells. In some embodiments, a gene editing system comprises a Cas protein, and the system further comprises a guide RNA (gRNA) that complexes with the Cas protein. In some embodiments, the gene editing moiety comprises an RBP complexed with a gRNA that is able to form a complex with a Cas protein. In some embodiments, the gRNA comprises a targeting segment which exhibits 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%, or at least 99%, or 100% sequence identity to a target polynucleotide. Multiple gRNAs can be used, e.g., to simultaneously or sequentially target TRAC, TRBC1, and / or TRBC2. In some cases, a dual nickase approach may be used to introduce a double stranded break. Cas proteins can be mutated at certain amino acids within either nuclease domains, thereby deleting activity of one nuclease domain and generating a nickase Cas protein capable of generating a single strand break. A nickase along with two distinct guide RNAs targeting opposite strands may be utilized to generate a DSB within a target site (often referred to as a "double nick" or "dual nickase" CRISPR system). A transposon-based system can be utilized for insertion of a recombinant nucleic acid encoding a binding protein of the disclosure or a component thereof into a genome, or for disruption of a TCR encoding gene. A transposon can comprise a recombinant nucleic acid that can be inserted into a DNA sequence. A class I transposon can be transcribed into an RNA intermediate, then reverse transcribed and inserted into a DNA sequence. A class II transposon can comprise a DNA sequence that is excised from one DNA sequence and / or inserted into another DNA sequence. A class II transposon system can comprise (i) a transposon vector that contains a sequence (e.g., comprising a transgene) flanked by inverted terminal repeats, and (ii) a source for the transposase enzyme. A transposon system (e.g., class II transposon system) can direct the integration of a recombinant nucleic acid sequence encoding a binding protein or a component thereof, while leaving behind the rest of the vector. A transposon and a transposase can be introduced into a cell. In some cases, a vector that encodes a transposase and comprises a recombinant nucleic acid is introduced into a cell, and the transposase is expressed and mediates insertion of the transposon into the genome. Examples of transposon-based systems that can be used include, but are not limited to, sleeping beauty (e.g., derived from the genome of salmonid fish); piggyback (e.g., derived from lepidopteran cells and / or the Myotis lucifugus); mariner (e.g., derived from Drosophila); frog prince (e.g., derived from Rana pipiens); Tol2 (e.g., derived from medaka fish); and spinON. In some embodiments a binding protein or other polypeptide can be expressed in a host cell without genomic integration of a recombinant nucleic acid that encodes the binding protein or other polypeptide. For example, a binding protein or other polypeptide can be expressed from an episomal vector, such as a DNA, RNA, circular DNA, circular RNA, minicircle, and the like. A binding protein or other polypeptide can be transiently expressed. For example, expression of a binding protein or other polypeptide can be reduced as a nucleic acid that encodes it is degraded. One method of generating host cells is through the use of a ribonucleic acid (RNA) system, e.g., a system that involves delivering one or more recombinant nucleic acids as an RNA. In some cases, the use of RNA can minimize DNA-induced toxicity and immunogenicity sometimes observed with the use of DNA. In some cases, one or more recombinant nucleic acids of the disclosure can be inserted randomly into the genome of a cell. For instance, a recombinant nucleic acid can encode its own promoter or can be inserted into a position where it is under the control of an endogenous promoter. Alternatively or additionally, a recombinant nucleic acid can be inserted into a gene, such as an intron of a gene, an exon of a gene, a promoter, or a non-coding region. One or more recombinant nucleic acids and / or gene editing components can be delivered to a cell by any suitable method, for example, using any suitable vector. A vector can be or can comprise a viral vector, a gamma-retroviral vector, a lentiviral vector, an adeno-associated viral vector, a transposon, and the like. Any vector system can be used including, but not limited to, DNA vectors, RNA vectors, ribonucleoprotein vectors, hybrid DNA-RNA vectors, plasmid vectors, nanoplasmid vectors, minicircle vectors, retroviral vectors, lentiviral vectors, adenovirus vectors, poxvirus vectors; herpesvirus vectors and adeno-associated virus vectors, etc. Non-viral vector delivery systems can include DNA plasmids, naked nucleic acid, and nucleic acid complexed with a delivery vehicle such as a liposome, lipid nanoparticle, or poloxamer. Viral vector delivery systems can include DNA and RNA viruses, which have either episomal or integrated genomes after delivery to the cell. In some cases, one vector is used. In some cases, two vectors are used. In some cases, three or more vectors are used. In some cases, recombinant nucleic acids and / or gene editing components of the disclosure can be delivered to cells without the use of vectors. In some cases, one or more recombinant nucleic acids and / or gene editing components of the disclosure can be delivered to cells via vectors, and one or more recombinant nucleic acids and / or gene editing components can be delivered without the use of vectors. Cells can be genetically engineered to comprise a recombinant nucleic acid that encodes a binding protein and / or modification to reduce expression of TRAC, TRB, TRBC1, and / or TRBC2 ex vivo. For example, cells can be taken from a subject in one or more blood draws and / or apheresis procedures, modified ex vivo, optionally selected and / or expanded before and / or after genetic modification, and optionally re-introduced into the subject or a different subject by infusion or injection. In some cases, cells are genetically engineered to comprise a binding protein of the disclosure and / or modification to reduce expression of endogenous TRAC, TRB, TRBC1, and / or TRBC2 in vivo. For example, a vector can be used to deliver gene editing components to cells in a subject without removing the cells from the subject. Vectors can be delivered in vivo by administration to an individual subject, for example, by parenteral administration (e.g., intravenous, intraperitoneal, intramuscular, subdermal, or intracranial infusion) or topical application. Methods to introduce gene editing components into a cell include, but are not limited to, electroporation, sonoporation, use of a gene gun, lipofection, calcium phosphate transfection, use of dendrimers, microinjection, and use of viral vectors including adenoviral, AAV, and retroviral vectors. Electroporation using, for example, the Neon® Transfection System (ThermoFisher Scientific), the Xenon Electroporation System (ThermoFisher Scientific), or the AMAXA® Nucleofector (AMAXA® Biosystems) can also be used for delivery of nucleic acids into a cell. Electroporation parameters may be adjusted to optimize transfection efficiency and / or cell viability. Electroporation devices can have multiple electrical wave form pulse settings such as exponential decay, time constant and square wave. Every cell type has a unique optimal Field Strength (E) that is dependent on the pulse parameters applied (e.g., voltage, capacitance and resistance). Application of optimal field strength causes electropermeabilization through induction of transmembrane voltage, which allows nucleic acids to pass through the cell membrane. In some cases, the electroporation pulse voltage, the electroporation pulse width, number of pulses, cell density, and tip type may be adjusted to optimize transfection efficiency and / or cell viability. Cells can be selected or enriched for having or not having one or more given factors (e.g., cells may be separated based on the presence or absence of one or more factors). Selection techniques include positive selection and negative selection techniques, e.g., fluorescent activated cell sorting (FACS) or magnetic activated cell sorting (MACS). In some cases, cells can be selected before gene editing, for example, to enrich for a population of cells disclosed herein (e.g., immune cells, such as T cells or a T cell subset disclosed herein, such as gamma delta T cells or alpha beta T cells). Cells can be selected after gene editing, for example, to enrich for a population of cells disclosed herein (e.g., host cells that express a binding protein or additional polypeptide, and / or comprise a modification to reduce expression of endogenous TRAC, TRB, TRBC1, and / or TRBC2). Host cells can be selected or enriched based on a tag or marker, such as an epitope tag. The tag or marker can be appended to the binding protein. In some embodiments, the tag or marker is not appended to the binding protein. The tag or marker can be co-expressed with the binding protein as disclosed herein. The tag or marker can comprise a reporter gene, such as a fluorescent protein. Cells can be selected, enriched, or expanded on the basis of being positive or negative for a given factor. In some embodiments, cells are selected, enriched, or expanded on the basis of being positive for two or more factors. In some embodiments, cells can be selected, enriched, or expanded on the basis of being positive for one or more factors, and negative for one or more factors. In some cases, a selectable marker is introduced to a cell, e.g., together with or as part of a recombinant nucleic acid encoding a binding protein, so that cells that comprise the binding protein or modification express the selectable marker and can be selected, enriched, or expanded. In some cases, a selectable marker is an antibiotic resistance gene, and cells that do not express the antibiotic resistance gene can be killed by treatment with the antibiotic (e.g., to select or enrich for cells that comprise a binding protein). In some embodiments, the selectable marker is an epitope tag. In some embodiments, the selectable marker comprises a FasBB polypeptide. In embodiments, the selectable marker (e.g., FasBB) may be used in combination with a selection agent (e.g., Fas ligand (FasL)), to enrich a population of cells for genetically modified host cells. Methods for enriching a population of cells for genetically modified cells expressing a selectable marker (e.g., FasBB polypeptide) may accordingly involve contacting the population of cells with a selection agent (e.g., FasL), and may further involve selecting viable cells after contacting the population of cells with the selection agent. Expression of a binding protein, TRAC, TRB, TRBC1, and / or TRBC2 of the disclosure can be quantified, for example, by qPCR, RNA sequencing, western blot, or flow cytometry. In some embodiments, selected cells can be expanded ex vivo and / or in vitro before gene editing or delivery of a recombinant nucleic acid, after gene editing or delivery of a recombinant nucleic acid, before selection, after selection, before expansion, after expansion, or a combination thereof. In some embodiments, selected cells can be expanded ex vivo and / or in vitro before gene editing or delivery of a recombinant nucleic acid. In some embodiments, selected cells can be expanded ex vivo and / or in vitro after gene editing or delivery of a recombinant nucleic acid. In some embodiments, selected cells can be expanded ex vivo and / or in vitro before selection and / or enrichment. In some embodiments, selected cells can be expanded ex vivo and / or in vitro after selection and / or enrichment. In some embodiments, selected cells can be expanded ex vivo and / or in vitro before expansion. In some embodiments, selected cells can be expanded ex vivo and / or in vitro after expansion. Kits The instant disclosure also provides kits containing agents of this disclosure for use in the methods of the present disclosure. Kits of the instant disclosure may include one or more containers comprising an agent for treatment of a neoplasia. In some embodiments, the kits further include instructions for use in accordance with the methods of this disclosure. In some embodiments, these instructions comprise a description of use of the agent to treat, e.g., a neoplasia, according to any of the methods of this disclosure. Instructions supplied in the kits of the instant disclosure are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine-readable instructions (e.g., instructions carried on a magnetic or optical storage disk) are also acceptable. Instructions may be provided for practicing any of the methods described herein. The kits of this disclosure are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging (e.g., sealed Mylar or plastic bags), and the like. Kits may optionally provide additional components such as buffers and interpretive information. Normally, the kit comprises a container and a label or package insert(s) on or associated with the container. The practice of the present invention employs, unless otherwise indicated, conventional techniques of molecular biology (including recombinant techniques), microbiology, cell biology, biochemistry and immunology, which are well within the purview of the skilled artisan. Such techniques are explained fully in the literature, such as, "Molecular Cloning: A Laboratory Manual", second edition (Sambrook, 1989); "Oligonucleotide Synthesis" (Gait, 1984); "Animal Cell Culture" (Freshney, 1987); "Methods in Enzymology" "Handbook of Experimental Immunology" (Weir, 1996); "Gene Transfer Vectors for Mammalian Cells" (Miller and Calos, 1987); "Current Protocols in Molecular Biology" (Ausubel, 1987); "PCR: The Polymerase Chain Reaction", (Mullis, 1994); "Current Protocols in Immunology" (Coligan, 1991). These techniques are applicable to the production of the polynucleotides and polypeptides of the invention, and, as such, may be considered in making and practicing the invention. Particularly useful techniques for particular embodiments will be discussed in the sections that follow. The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the assay, screening, and therapeutic methods of the invention, and are not intended to limit the scope of what the inventors regard as their invention.

[0003] EXAMPLES Example 1: TCR-T cells expressing an exogenous TCR and a CD8αβ coreceptor show strong specificity for p53 R175H. Twelve T cell receptors (TCRs) that recognize a p53 R175H peptide were evaluated (TCRs 1-12, Table 1). Aside from an instance of vendor error, the twelve TCRs demonstrated high transduction efficiency into T cells, whether transduced with a construct encoding only the TCR (either in original form or modified to comprise a cysteine residue) or transduced with a construct encoding the TCR and a CD8αβ co-receptor (FIG.1). TCR-T cells modified to express the exogenous TCRs with and without co-expression of the CD8αβ co-receptor were evaluated for cell surface expression and function (i.e., recognition of HLA-A*02-p53 R175H peptide complexes. Specifically, cell surface expression of correctly paired alpha and beta chains of TCRs 1-12 and these TCR’s abilities to bind p53 R175H peptides presented in an HLA-A*02 context was assessed using fluorophore labeled tetramers of MHC-peptide complex. Inclusion of the CD8αβ co-receptor in the construct transduced into the T cells led to increases in the mean fluorescence intensity (MFI, reflecting average signal per cell) for the majority of TCRs tested and especially in CD4 T cells (FIG.2). To evaluate TCR sensitivity to p53 R175H, T cells transduced to express TCR1-7 and 9- 12 (TCR-T cells), with and without the CD8αβ co-receptor, were co-incubated with T2 cells loaded with p53 peptides comprising the R175H mutation (T2 cells express an empty MHC molecule). The TCR-T cells showed high activation sensitivity for p53 R175H peptide, as measured by expression of CD137 (FIGs.3A-3B, Table 3). Table 3: EC50 To evaluate the cytotoxic activity of TCR-T cells expressing one of TCR1-7 and 9-12, tumor cells (e.g., TKY-nu (a human ovarian cancer cell line) and KLE cells (an endometrial carcinoma cell line)) were modified to express a red fluorescent protein and cocultured with TCR-T cells at a 5:1 effector:target cell ratios. Total red object integrated intensity (a measure of tumor cell volume or tumor confluence) was evaluated over time. Red fluorescence was measured by live cell imaging using a live cell analysis system, the IncuCyte S3 microscope and software package. CD8+T cell cytotoxicity is indicated by a decrease in the total red target cell area (tumor confluence) per well as compared to no treatment wells. Several TCR-T cells exhibited cytotoxic activity. (FIGs.4A-4B). A subset of these TCR-T cells were further evaluated at a 3:1 effector cell to target cell ratio and exhibited cytotoxic activity (FIG.5). The specificity of lead candidates (TCR-T cells expressing TCR 2, 3, 6, or 9) for p53 R175H was further evaluated for TCR-T cell activation and cytotoxic activity against non-target peptides and antigen negative cell lines, respectively. These cells were activated (as measured by IFNgamma) when co-incubated with T2 cells loaded with mutant but not wild type peptides (or unloaded ("unpulsed")). The TCR-T cells showed no discernable difference in cytotoxic activity against CFPAC cells (i.e., antigen negative cells modified to express a red fluorescent protein) relative to control (FIGs.6A-6B) when evaluated as described above. To assess potential TCR off-target activity, CD4+ / CD8+ T cells expressing TCR9 disclosed herein were cultured overnight with a panel of positional scanning peptides containing a substitution of every possible amino acid at each position of the cognate p53 R175H peptide. Secreted IFNγ levels were determined to identify TCR cross-reactivity to promiscuous positions. Potentially antigenic peptides were then matched against the human proteome to predict potential in vivo off-targets using ScanProsite (prosite.expasy.org / scanprosite / ). Peptides that elicited a response of greater than 10% of the maximum signal were considered positive in this assay. Few or no potential off-targets were identified for p53-R175H-recognizing TCR9. (FIG.7A). Of the X-Scan predicted potential off-targets in the human genome only 4 surpassed 10% activity of index peptide (STAT, CEP128, FRK, and VATF). However, all were at least 1000-fold less sensitive suggesting low probability of autoreactivity (FIG.7B). Example 2: TCR-T cells armored with a FasBB switch receptor and an ILR fusion protein have advantageous properties Double knockout primary CD4 / CD8 TCR-T cells were generated by targeted disruption of the T cell receptor beta constant (TRBC) locus and by targeted insertion into the TRAC locus of a construct encoding an exogenous TCR (TCR9, see Table 1) and a CD8αβ co-receptor (SEQ ID NO:Y). The construct further encoded either a FasBB switch receptor (SEQ ID NO: 263) comprising a Fas extracellular domain and a 4-1BB intracellular signaling domain or an ILR fusion protein comprising a CD34 extracellular domain and an IL7Rα intracellular domain separated by a transmembrane domain (SEQ ID NOs: 387, 278, 291, respectively) or both the FasBB switch receptor and the ILR fusion protein. The encoded functional elements (i.e., TCR alpha and beta chains, CD8α, CD8β, FasBB, and ILR) of each construct were separated by sequences encoding a P2A or T2A self-cleaving peptide. Knock-in efficiency of the construct into the TRAC locus as determined by the percentage of cells expressing a 2A peptide after 6 and 12 days post-knock-in was greater for those constructs encoding the ILR fusion protein alone or the ILR fusion protein and the FasBB switch receptor (FIG.8A). Transgene expression was similar between primary CD4 / CD8 TCR- T cells genetically-engineered with knock-in constructs encoding 4 transgenes (TCR alpha and beta chains, CD8α, and CD8β), 5 transgenes (TCR alpha and beta chains, CD8α, CD8β, and FasBB or ILR), or 6 transgenes (TCR alpha and beta chains, CD8α, CD8β, FasBB, and ILR) demonstrating minimal impact of length or position within the construct (FIG.8B). Single knockout T cells were also generated by targeted insertion of the constructs described above in this example. Knock-in efficiency was again greater for those constructs encoding ILR or FasBB and ILR (FIG.8C). As with the modified double knockout cells, transgene expression was similar between primary CD4 / CD8 single knockout TCR-T cells genetically-engineered with knock-in constructs encoding 4, 5, or 6 transgenes (FIG.8D). Double knockout TCR-T cells expressing the exogenous TCR9 and CD8αβ coreceptor and either an ILR fusion protein, a FasBB switch receptor, or both the ILR fusion protein and the FasBB switch receptor were shown to be sensitive to p53 R175H mutant peptide. Activation of the TCR-T cells was assessed by co-incubating the TCR-T cells with T2 cells pulsed with p53 R175H cognate peptide and then detecting IFNgamma expression and the percentage of cells expressing CD137 (FIGs.9A-9B; similar data for single knockout T cells not shown). Double knockout TCR-T cells expressing TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB were able to kill Tyk-nu and KLE cells when cocultured at a 3:1 target:effector cell ratio (FIGs.10A, 10B; cytotoxic activity was measured as described above). Similarly, single knockout TCR-T cells expressing TCR9, CD8αβ coreceptor, ILR, and FasBB were also able to kill Tyk-nu and KLE cells when cocultured at a 3:1 target:effector cell ratio (FIGs.10C, 10D; cytotoxic activity was measured as described above). No killing activity was observed when the TCR-T cells were co-incubated with a negative control cell line (CFPAC). (FIGs.10E). Additionally, armored TCR-T cells (i.e., expressing ILR, FasBB or ILR and FasBB were more persistent than unarmored TCR-T cells (FIGs.11A, 11B (double knockout TCR-T cells) and FIGs.11C-11D (single knockout TCR-T cells)). Activation and cytotoxic activity of TCR-T cells expressing TCR9, CD8αβ coreceptor, and ILR or FasBB or ILR and FasBB were evaluated in the presence of tumor cells. TCR-T cells were activated (as measured by IFNγ and GrzB expression) when co-cultured with a KLE cells, but not for a negative cells line (FIGs.12A,12B (double knockout TCR-T cells) and FIGs. 12C-12D (single knockout TCR-T cells)). TCR-T cells modified to express the TCRs and CD8αβ coreceptor with or without ILR and FasBB did not kill tumor cells not expressing both HLA-A*02 and p53 R175H (FIG.13). Example 3: TCR-T cells expressing a FasBB switch receptor are active in the presence of Fas ligand. To determine if TCR-T cells of the present disclosure had a survival advantage over unengineered T cells in the presence of Fas ligand (FasL), unengineered T cells and engineered TCR-T cells were incubated with recombinant FasL. Unengineered T cells did not survive in the presence of recombinant FasL (FIG.14A). However, TCR-T cells modified by knockout of TRBC and by non-viral knock-in at the TRAC locus with a construct encoding TCR9, CD8αβ coreceptor, a FasBB switch receptor or an ILR fusion protein and FasBB switch receptor were able to survive in the presence of FasL, but TCR-T cells modified to express only the TCR, CD8αβ coreceptor, and ILR fusion protein did not (FIG.14B). Additionally, only those TCR-T cells modified to express the FasBB switch receptor or the FasBB switch receptor and the ILR fusion protein were able to kill TYK-nu tumor cells modified to express FasL (FIG.15A). When coincubated with TYK-nu cells that did not express FasL, TCR-T cells expressing TCR9, CD8αβ coreceptor, and the ILR fusion protein or the ILR fusion protein and FasBB controlled TYK-nu growth (FIG.15B). Cryopreserved double knockout (DKO) and single knockout (SKO) TCR-T cells expressing the FasBB switch receptor and the ILR fusion protein were thawed in cytokine- containing or cytokine-free medium failed to survive when cultured in media lacking interleukin 2 (IL2), interleukin 7 (IL7), and interleukin 15 (IL15) (FIGs.16A (DKO) and 16B (SKO)). Additionally, recombinant FasL was added at concentration previously showed to be active in the killing assay, and yet TCR-T cells expressing FasBB and ILR didn’t persist in the absence of exogenous cytokine despite receiving costimulation from FasBB and IL7R signaling (FIG.16C). Lack of persistence in the absence of exogenous cytokines and in the presence of FasL supports a potential tolerability profile of the TCR-T cells. Example 4: In vivo efficacy of TCR-T cells Nod scid gamma (NSG) mice were implanted subcutaneously with TYK-nu cells, randomized (n = 5 per group) and treated 20 days post-implant with 10 x 106T cells administered intravenously (unengineered T cells or TCR-T cells expressing TCR9 with co- expression of a CD8 co-receptor, FasBB, and ILR and knockout of endogenous TRAC and TRBC). A 1:1 ratio of CD4+ and CD8+ T cells was administered. The engineered cells demonstrated robust anti-tumor efficacy as demonstrated by control of TYK-nu tumor volume (FIG.17A). In the study period, 100% complete responses and 100% survival was observed for the group administered the TCR-T cells. Additionally, no animal weight changes were observed between animals treated with TCR-T cells or control cells (FIG.17A inset). Single knockout TCR-T cells also were able to control subcutaneous TYK-nu tumor growth in vivo, with two groups of mice achieving a complete response in the absence of body weight loss for over 80 days (FIG.17B). Example 5: Genetically modified cells are enriched by treatment with Fas ligand (FasL) Experiments were performed to determine if cells genetically modified to express a FasBB switch receptor could be enriched by treating the cells with Fas ligand (FasL) after modification (i.e., knock-in of the cassette encoding an anti-p53 TCR (i.e., TCR6 or TCR9), CD8αβ coreceptor, an ILR fusion protein, and a FasBB switch receptor. 5 x 106viable T cells were collected for each condition and harvested into 15 mL conical tubes and spun at 200 x g for 7 minutes to pellet cells. Cell pellets were resuspended at 1 x 106in 2% PLT Gold X-Vivo 15 (Lonza, Basel, Switzerland). T cells were plated for apoptosis induction as follows: Plate 1:100 μL per plate into a 96-well U-bottom plate, and 50 μL of media was to each well to normalize volumes to 150 μL per well. A 2X dilution series was prepared of recombinant human Fas ligand (rhFasL) (Abcam, Waltham, MA) with each point 4x final concentration. Stock rhFasL (10 μg) was resuspended in 100 μL H2O - stock, 100,000 ng / mL. 2X dilution series was prepared. 50 μL of each concentration of rhFasL in the dilution series was added to each well of a corresponding row on the cell plate (final volume of each well was 200 μL). The plate was then incubated overnight at 37°C. The results showed enrichment of cells co-expressing a TCR disclosed herein with a FasBB fusion protein as compared to cells not expressing the FasBB fusion protein after treatment with increasing concentrations of Fas ligand (rhFASL) (FIG.18). Fas ligand-mediated enrichment of TCR-T cells Stain 1: Zombie NIR and Apotracker Green Staining To detect dead and apoptotic cells, cell pellets were resuspended in 100 μl Zombie NIR (Biolegend, San Diego, CA; at a 500x dilution factor) and Apotracker Green (Biolegend) (at 5 μL per test) containing PBS and incubated at room temp for 10-20 minutes. Zombie NIR was quenched by adding an equal volume of BSA-containing buffer to each well. Cells were spun down at 300 x g for 2 minutes, and the supernatant was discarded. Stain 2: Surface Staining Surface stain (Table 4) was added to Stain 1 cell pellets, mixed by pipetting, and then incubated at 4°C for 30 minutes. Cells were then spun down at 400 x g for 3 minutes and the supernatant discarded. The cell pellets were washed 2X with 200 μl staining buffer, and samples were floated in stain buffer. Table 4: Surface mAb Stain Master Mix 2A Staining Cell samples were fixed and permeabilized (BD Cytofix / Cytoperm™ Fixation / Permeabilization Kit (BD Biosciences, Franklin Lakes, NJ; Cat. No.554714)) in 96-well U bottom plates. 1X BD Perm / Wash™ Buffer was prepared by diluting 10X BD Perm / Wash™ Buffer with water. Plates were then spun at 300 x g for 2 minutes, and the supernatant was discarded. Cells were resuspended in 100 μl of Fixation / Permeabilization solution and fixed on ice for 20 minutes. Cells were spun down at 400 x g for 3 minutes, and the supernatant was discarded. Cell pellets were washed twice with 200 μl of 1X BD Perm / WashTMBuffer. Cells were resuspended in 100 μl intracellular antibody (anti-2A1) containing 1x BD Perm / WashTMBuffer and incubated on ice for 30 minutes. Cells were then spun down at 400 x g for three minutes, washed with 200 μl 1x BD Perm / WashTMBuffer. The cells were spun down again at 400 x g for three minutes and washed with 200 μl of staining buffer. The cells were spun down again at 400 x g for three minutes and resuspended in 100 μl of 1% PFA. Samples were fixed in 1% PFA diluted in PBS. Each pellet was resuspended in 40 μl 1%PFA. Fluorescent activated cell sorting (FACS) was then performed. Methods The above Examples were carried out using the following methods and materials. ILR Fusion Protein A polynucleotide sequence encoding the fusion protein comprising a CD34 extracellular domain fused to an IL7Rα intracellular domain and transmembrane domain used in the above Examples is found below: >CD34IL7Rα ATGCTCGTCAGAAGAGGCGCTAGAGCCGGACCTAGAATGCCCAGAGGATGGACAGCCCTCTGCCTCCTGTCTCTGCT GCCTAGCGGCTTCATGAGCCTGGACAACAACGGCACAGCCACACCTGAGCTGCCTACACAGGGCACCTTCAGCAATG TGTCCACAAACGTGTCCTACCAAGAGACAACCACACCTAGCACACTGGGCAGCACATCTCTGCACCCTGTGTCTCAG CACGGCAATGAGGCCACCACCAATATCACCGAGACAACCGTGAAGTTCACCAGCACCAGCGTGATCACCTCCGTGTA CGGCAACACCAACAGCAGCGTGCAGAGCCAGACCTCCGTGATCAGCACCGTGTTTACAACCCCTGCCAATGTGTCTA CCCCTGAGACAACTCTGAAGCCCAGCCTGTCTCCTGGGAACGTGTCCGATCTGAGCACCACCTCTACCAGCCTGGCC ACCTCTCCTACAAAGCCCTACACAAGCAGCAGCCCCATCCTGAGCGATATCAAGGCCGAAATCAAGTGCAGCGGCAT CCGGGAAGTGAAACTGACCCAGGGCATCTGCCTGGAACAGAACAAGACCAGCAGCTGCGCCGAGTTCAAGAAGGACA GAGGCGAAGGACTGGCCAGAGTGCTGTGTGGCGAAGAACAGGCCGATGCTGATGCTGGCGCTCAAGTCTGTTCACTG CTGCTGGCCCAGTCTGAAGTGCGGCCTCAATGTCTGCTTCTGGTCCTGGCCAACCGGACCGAGATCTCTAGCAAACT GCAGCTGATGAAGAAGCACCAGAGCGACCTGAAGAAGCTGGGCATCCTGGACTTCACCGAGCAGGATGTGGCCAGCC ACCAGAGCTACAGCCAGAAAACACCTATCCTGCTGACCTGTCCGACAATCAGCATCCTGTCCTTTTTCAGCGTGGCC CTGCTCGTGATCCTGGCCTGTGTGCTGTGGAAGAAGCGGATCAAGCCCATCGTGTGGCCTAGCCTGCCTGACCACAA AAAGACCCTGGAACACCTGTGCAAAAAGCCCCGGAAGAACCTGAATGTGTCTTTCAACCCCGAGAGCTTCCTGGACT GCCAGATCCACAGAGTGGACGACATCCAGGCCAGAGATGAGGTGGAAGGCTTTCTGCAGGACACCTTTCCGCAGCAG CTGGAAGAGTCCGAGAAGCAGAGACTCGGCGGAGATGTGCAGTCCCCTAATTGCCCTAGCGAGGACGTGGTCATCAC CCCTGAGTCCTTCGGAAGAGACTCCAGCCTGACTTGTCTGGCCGGAAATGTGTCTGCCTGCGACGCCCCTATCCTGT CCAGCTCTAGAAGCCTGGACTGTAGAGAGAGCGGCAAGAACGGCCCTCATGTGTACCAGGATCTGCTGCTGTCCCTG GGCACCACCAACTCTACACTGCCTCCACCATTCAGCCTGCAGTCCGGCATCCTGACACTGAATCCTGTGGCTCAGGG CCAGCCAATCCTGACAAGCCTGGGCTCCAATCAAGAAGAGGCTTACGTCACCATGAGCAGCTTCTACCAGAATCAA (SEQ ID NO: 389) Genome Editing at TRAC and TRBC loci CRISPR-mediated disruption of TRAC and TRBC was carried out using the following protocol. On day 0, 100 x106CD4+ or CD8+ T cells were thawed and transactivated (with 1:100 Transact). Cells were cultured in a 6-well G-rex plate (~ 25 x106cells / well). Approximately 45-55% of cells died by day 2; the number of cells was therefore calculated according to the conditions needed for knockout (KO) on day 2. T cells were cultured in complete T cell media comprising XVivoTM15 Serum-free Hematopoietic Cell Medium (Lonza, Basel, Switzerland), 2% PLT-gold, 100 IU / mL IL-2, 500U / ml IL-7, and + 500U / ml IL-15. On day 1, T cells were transduced with lentivirus encoding an extracellular binding protein as described herein (e.g., a p53 mutant-specific TCR or any of the TCR sequences recited in TABLE 1) or were left as-is to transactivate until day 2. If transducing with lentivirus (LV), cells were counted and transduced at 5-10 x106cells per condition. On day 2, cells were electroporated with ribonucleoprotein complexes (RNPs) to knock out TRAC and / or TRBC1 / 2 genes (e.g., using the guide RNAs in SEQ ID NO: 113 or 115). For each electroporation, 100-250 pmol guide RNA and enough nuclease for a 2.5:1 guide RNA to nuclease ratio (MG-29) was assembled in 7.5 µL total volume at room temperature for 30 minutes to form RNP complexes. While RNP complexes were forming, cells were counted and 5-10 x106cells were used per electroporation for the 100 µL electroporate volume using Neon (ThermoFisher). If cells were transduced on day 1, cells were generally not counted again on day 2. To set up the Neon electroporator, CTS Xenon electroporation buffer (Thermo Cat# A4997901) and E2 buffers were first thawed to room temperature in BSE. E2 Electrolytic buffer is a high osmolarity buffer that is commercially available from ThermoFisher Scientific. The required volume of electroporation buffer was then transferred in a microfuge or 15 mL tube. 7 mL of complete T cell media (X-VIVO15 (Lonza, (Lexington, MA) 04-418Q) + 2% PLTGold (Mill Creek Life Sciences (Rochester, MN) PLTGOLD100 GMP) was then added to each well of a 24 well plate used for non-adherent cell propagation, which was commercially available as Grex plate, and transferred to 37°C (for culturing cells after they had been electroporated). Subsequently, 5-10 x106cells per electroporation condition were spun down in 15 mL tubes. The media was carefully aspirated and the cell pellet resuspended with 100 µL GE electroporation buffer (if performing single KO (sKO)) or 95 µL GE electroporation buffer (if performing double KO (dKO)). The cell media was aspirated, and the cell pellet was left as-is in the BSE for 15-20 mins until ready for electroporation. The total volume desired for electroporation was 120 µL. If performing dKO, the TRAC RNP was combined with TRBC RNP (7.5 µL each for required number of conditions). 7.5 µL of RNP (after the 30min incubation) was added if doing sKO or 15 µL of RNP if doing dKO to the cells in GE buffer. The cells and RNP were mixed by gently flicking the tube. Approximately 100 µL of the mix containing RNP and electroporation buffer was carefully pipetted using the Neon 100 µL pipettor and tip. Care was taken to have no bubbles in the pipet tip. If bubbles formed despite 2-3 attempts, the tip was changed or 10-15 µL of electroporation buffer was added to the tube and the step was repeated. 3 mL of E2 buffer was then transferred to a Neon electroporation tube and placed in a tube holder. The electroporation pipet with tip containing cells and RNP was transferred to the tube containing E2 buffer in the tube holder, and the electroporation protocol on the Neon was carried out using suitable settings on the electroporator. An example setting for the Neon electroporator was 2300V, 4 pulses, and 3 ms pulse width. After electroporation, the cells were then transferred to a well of a 24 well plate (standard tissue culture (TC) plate can be adherent or non-adherent) – ElectroPoration (“EP plate”) and incubated in BSE at room temperature for about 10 minutes. About 1 mL of T cell media from G-rex plate was added dropwise to electroporated cells. Cells were gently pipeted once and transferred to the G-rex well. Another 1ml was used to wash cells out of the 24 well EP plate and transferred to wells in the G-rex plate. The plate was returned to 37°C with 5% CO2. SgRNAs used in the Examples above to target the TRAC or TRBC locus comprised a crRNA, linker, and transRNA. Sequences of the crRNAs are provided below: >TRAC crRNA GAGTCTCTCAGCTGGTAC^ACGG^ (SEQ ID NO: 390) >TRBC crRNA AGCCATCAGAAGCAGAGA^TCNN^ (SEQ ID NO: 391) Exemplary Non-viral transgene integration (knock-in) protocol This example provides illustrative methods for non-viral knock-in of a transgene / expression cassette combined with knockout of TRAC, TRBC1, and / or TRBC2. Materials: (i) T-cell donor of interest; (ii) Nanoplasmid (5mg / mL stock); (iii) X-Vivo-15, with cytokines (IL2, IL7 and IL15) and 2% PLT-Gold; (iv) 6 and 24 Well GREX Plate; (v) CTS Xenon Electroporation Buffer (Gibco, Cat# A4997901) or CTS Xenon Genome Editing Buffer (Gibco, Cat# A4998001); (vi) 96 well flat bottom plate (assay plate); (vii) 96 well U bottom plate (staining plate); (viii) Miltenyi T-cell activating Transact (Miltenyi, Cat# 130-111-160); (ix) Antibodies for: CD4, CD8, TCRab, P2A, Live / Dead, tetramer peptide conjugate; (x) BD CytoFix; and (xi) 10x BD Perm / Wash.. Day 0: Thawing cells. Fresh medium for thawing T-cells comprised either X-vivo 15 + 2% PLT-gold + IL2 (100 Units), IL7( 500U / ml, and IL15 (500 U / ml. The cells were subjected to a rapid thaw and then resuspended in complete medium (e.g., a final volume of 10 mL). T cells were counted (Celleca, AOPI staining) to determine number of cells and viability. The T cells were spun at 300 x g for 5 minutes, and the medium was then removed and the cell pellet was responded in 1 mL of fresh media. The resuspended cells were transferred to a well on a 6-well GREX plate (about 24 mL of medium per well). The well was supplemented with 1:100 Miltenyi Transact (e.g., 250 µL for 25 mL medium) to activate the T cells and incubated at 37C and 5% CO2 for 44-48hr . Day 2: Electroporation for knocking-in transgene cassette at the TRAC locus RNP was complexed at a 2.5:1 nuclease to guide molar ratio for 20-30 minutes at room temperature: (a) sgRNA (300 µM stock): 2.1 µL; (b) MG-21 nuclease (6.93 mg / mL stock): 5.4 µL; (c) Total RNP per single reaction: ~7.5 µL. While the RNP complexed at room temperature, donor T-cells were resuspended, pooled, and counted. T cells were collected and spun down 300 x g for 5 minutes. Neon electroporation reactions used 5 x106cells per reaction, and Xenon electroporation reactions used 50 x106cells per reaction. Post-EP medium was X-vivo medium + IL 2 (100U / ml), 7 (500U / ml), 15 (500U / ml), with 2% PLT gold. If double knock outs (dKO) were performed, the respective RNPs were mixed 1:1 for easier pipetting (15 µL per EP reaction in Neon, 150 µL for Xenon). Cells were pelleted and only resuspended in EP buffer when ready to electroporate, as buffer can be toxic to the cells. Neon electroporation option: reaction conditions include: (a) 100 µL electroporation buffer to resuspend cells; (b) 7.5 µL per RNP (7.5 ul for sKO; 15ul for dKO); (c) KI nanoplasmid if used at concentration of interest (20 µg): 4 µL plasmid; and (d) Electroporation: 2300 V, 4 pulses, 3 ms pulse width. An electroporation tube was placed in the electroporation unit, and the tube was filled with 3-5 mL of E2 buffer to connect the conductors. T he electroporation tip was attached to the syringe (press down hard to attach, gold plated conductor rod should not be more than 30% of the way down on a non-depressed syringe). The syringe was used to gently pipette the sample and draw it into the tip. No bubbles should be present in the tip at the top as it interferes with electroporation. Once loaded into the Neon Tip, the sample was transferred to the casing and the syringe was clicked into place in the tube. The Neon electroporator was run. The cells were transferred to a 24 well flat bottom plate to allow cells to rest for 20-40 minutes at room temperature in the BSE. 1 mL of medium was taken from the final destination well and added dropwise to cells to gently resuspend the rested cells. Cells were incubated at 37°C to allow growth and count cells on day 4. Xenon electroporation option: reaction conditions included: (a) 800 µL electroporation buffer to resuspend cells; (b) 200 µL Master Editing Mix (see below); and (c) EP Protocol: 2300 V, 4 pulses, 3 ms pulse width, 500 ms pulse interval. 200 µL Master mix of RNP, buffer (the same as for Neon electroporation), and nanoplasmid (or other nucleic acid molecule): 75 µL per RNP, 40 µL nanoplasmid (200 µg, if using), Q.S. using electroporation buffer to 200 µL. Cells were pelleted at 300 x g for 5 minutes. Pellet was resuspended in 800 µL of buffer. 200 µL Editing Master Mix was added to the 800 µL. Entire volume (1 mL) was transferred into a Xenon One Shot cartridge by removing the top and filling the unit. Cell solution should be slightly convex to ensure contact with the conductor at the top of the cartridge. Xenon One Shot cartridge was inserted into the instrument and the electroporator was run. Cells were removed and allowed to rest in the cartridge for 10 minutes before transferring into 40 mL Xvivo15 + 2% PLT-gold + cytokines and incubating at 37°C. On the following day, 60 mL of fresh medium was added to the well. Other Embodiments From the foregoing description, it will be apparent that variations and modifications may be made to the invention described herein to adapt it to various usages and conditions. Such embodiments are also within the scope of the following claims. The recitation of a listing of elements in any definition of a variable herein includes definitions of that variable as any single element or combination (or subcombination) of listed elements. The recitation of an embodiment herein includes that embodiment as any single embodiment or in combination with any other embodiments or portions thereof. All patents and publications mentioned in this specification are herein incorporated by reference to the same extent as if each independent patent and publication was specifically and individually indicated to be incorporated by reference.

Claims

What is claimed is:

1. An engineered cell comprising a heterologous T cell receptor (TCR) that specifically binds a mutant form of p53 peptide present in a peptide:HLA complex; a CD8 co-receptor; and a switch receptor comprising a FAS extracellular domain fused to 41BB intracellular signaling domain or a chimeric fusion polypeptide comprising an IL7 receptor alpha intracellular domain or both the switch receptor comprising a FAS extracellular domain fused to 41BB intracellular signaling domain and the chimeric fusion polypeptide comprising an IL7 receptor alpha intracellular domain.

2. The engineered cell of claim 1, wherein the peptide:HLA complex comprises an HLA protein encoded by an HLA-A*02 allele.

3. The engineered cell of claim 2, wherein the peptide:HLA complex comprises an HLA protein encoded by an HLA-A*02:01 allele.

4. The engineered cell of any one of claims 1-3, wherein the extracellular binding protein comprises a T cell receptor (TCR) α chain variable (Vα) region, a TCR β chain variable (Vβ) region, a T cell receptor (TCR) α chain constant (Cα) region, or a T cell receptor (TCR) β chain constant (Cβ) region 5. The engineered cell of any one of claims 1-4, wherein the mutant form of p53 peptide comprises an amino acid sequence HMTEVVRHC.

6. The engineered cell of any one of claims 1-4, wherein the mutant form of p53 is p53 R175H.

7. The engineered cell of claim 4, wherein the Vα domain or the Vβ domain are human, humanized, or chimeric.

8. The engineered cell of any one of claims 1-6, wherein the TCR is human, humanized, or chimeric.

9. The engineered cell of any one of claims 1-8, wherein the cell is an immune cell, or a precursor thereof.

10. The engineered cell of claim 9, wherein the immune cell comprises a T cell, a NK cell, a NK-T cell, a dendritic cell, a macrophage, a monocyte, or any combination thereof.

11. The engineered cell of any one of claims 1-10, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

12. The engineered cell of any one of claims 1-10, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; ora TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

13. The engineered cell of any one of claims 1-10, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

14. The engineered cell of any one of claims 1-10, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence of any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence of any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence of any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

15. The engineered cell of any one of claims 1-10, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO.

178.

16. The engineered cell of claim 12, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO.

178.

17. The engineered cell of claim 12, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO.

178.

18. The engineered cell of claim 12, wherein the TCR comprises a Vα comprising an amino acid sequence of SEQ ID NO.168 and a Vβ comprising an amino acid sequence of SEQ ID NO.

178.

19. The engineered cell of any one of claims 1-18, further comprising a genomic mutation that decreases expression of an endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), and / or T cell receptor β constant 2 (TRBC2).

20. The engineered cell of claim 19, wherein the genomic mutation that causes or contributes to decreased expression of the endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), or a T cell receptor β constant 2 (TRBC2) comprises an indel in the TRAC, TRBC1, or TRBC2 locus.

21. The engineered cell of claim 19, wherein the genomic mutation that causes or contributes to decreased expression of the endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), or T cell receptor β constant 2 (TRBC2) is a missense mutation that causes or contributes to reduced function or stability of a T cell receptor α or T cell receptor β polypeptide encoded by a genome of the cell.

22. The engineered cell of claim 19, wherein the genomic mutation that decreases expression of the endogenous T cell receptor α constant (TRAC), T cell receptor β constant 1 (TRBC1), or a T cell receptor β constant 2 (TRBC2) results in premature termination of a T cell receptor α or T cell receptor β polypeptide encoded by the endogenous TRAC, TRBC1, or TRBC2.

23. The engineered cell of claim 9, wherein the immune cell comprises a T cell, wherein the T cell comprises a CD4+T cell, a CD8+T cell, a CD4- CD8- double negative T cell, a γδ T cell, or any combination thereof.

24. The engineered cell of any of claims 1-23, wherein a) an α chain of the CD8 co-receptor comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 261; and / or b) a β chain of the CD8 co-receptor comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO:

262.

25. The engineered cell of any of claims 1-24, wherein the switch receptor comprises an amino acid sequence with at least 85% sequence identity to SEQ ID NO: 263 or 264.

26. The engineered cell of any of claims 1-25, wherein the chimeric fusion polypeptide comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs: 265, 266, 267, 268, 269, 270, 271, 272, 273, 274, 275, or 276.

27. An engineered cell comprising a polynucleotide encoding a heterologous T cell receptor (TCR) that specifically binds a mutant form of p53 peptide present in a peptide:HLA complex; a polynucleotide encoding a CD8 co-receptor; and a polynucleotide encoding a switch receptor comprising a FAS extracellular domain fused to 41BB intracellular signaling domain and / or a polynucleotide encoding a chimeric fusion polypeptide comprising an IL7 receptor alpha intracellular domain, wherein the engineered cell has decreased expression of TRAC1, TRBC1, or TRBC2.

28. The engineered cell of claim 27, wherein the polynucleotide encoding the heterologous TCR is inserted at a TRAC, TRBC1, or TRBC2 locus.

29. The engineered cell of claim 27 or 28, wherein the polynucleotide encoding the CD8 co- receptor is inserted at a TRAC, TRBC1, or TRBC2 locus.

30. The engineered cell of any one of claims 27-29, wherein the polynucleotide encoding the FAS extracellular domain fused to 41BB intracellular signaling domain is inserted at a TRAC, TRBC1, or TRBC2 locus.

31. The engineered cell of any one of claims 27-30, wherein the polynucleotide encoding the chimeric fusion polypeptide comprising the IL7 receptor alpha intracellular domain is inserted at a TRAC, TRBC1, or TRBC2 locus.

32. A polynucleotide encoding a TCR, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

33. A polynucleotide encoding a TCR, wherein the TCR comprises:a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

34. A polynucleotide encoding a TCR, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

35. A polynucleotide encoding a TCR, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence of any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence of any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; ora TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence of any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

36. A polynucleotide encoding a TCR, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO.

178.

37. A polynucleotide encoding a TCR, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO.

178.

38. A polynucleotide encoding a TCR, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO.

178.

39. A polynucleotide encoding a TCR, wherein the TCR comprises a Vα comprising an amino acid sequence of SEQ ID NO.168 and a Vβ comprising an amino acid sequence of SEQ ID NO.

178.

40. The polynucleotide of any one of claims 32-39, wherein the TCR specifically binds a mutant form of p53 peptide present in a peptide:HLA complex.

41. The polynucleotide of claim 40, wherein the mutant form of p53 is p53 R175H.

42. The polynucleotide of claim 40, wherein the mutant form of p53 comprises an amino acid sequence of HMTEVVRHC.

43. The polynucleotide of any one of claims 32-42, wherein the nucleic acid sequence is codon optimized.

44. The polynucleotide of any one of claims 32-43, wherein the extracellular binding protein is human, humanized, or chimeric.

45. The polynucleotide of any one of claims 32-44, further comprising a promoter.

46. The polynucleotide of claim 45, wherein the promoter is a murine stem cell virus (MSCV) promoter, an elongation factor-1 alpha (EF-1α) promoter, or a Meiotic Nuclear Divisions 1 (MND1) promoter.

47. The polynucleotide of any one of claims 32-46, wherein the polynucleotide comprises RNA, DNA, or a combination thereof.

48. A vector comprising the polynucleotide of any one of claims 32-47.

49. The vector of claim 48, wherein the vector is a lentiviral vector, a γ-retroviral vector, or an adeno-associated virus (AAV) vector.

50. A cell comprising the polynucleotide of any one of claims 32-46 or the vector of claim 48 or 49 51. A pharmaceutical composition comprising the engineered cell of any one of claims 1-31 and a pharmaceutically acceptable carrier, excipient, or diluent.

52. The pharmaceutical composition of claim 51, wherein the pharmaceutical composition comprises between about a 1:10 ratio to about a 10:1 ratio of CD4+ and CD8+ T cells53. A method of treating a neoplasia, the method comprising administering the engineered cell of any one of claims 1-31 or the pharmaceutical composition of claim 51 or 52 to a subject in need thereof.

54. The method of claim 53, wherein the neoplasia is a cancer selected from the group consisting of a colorectal cancer, esophageal cancer, head and neck cancer, larynx cancer, lung cancer, breast cancer, endometrial cancer, and ovarian cancer.

55. The method of claim 54, wherein the lung cancer is small cell lung cancer or squamous cell lung cancer.

56. The method of claim 54, wherein the breast cancer is triple-negative breast cancer.

57. The method of claim 54, wherein the ovarian cancer is high-grade serous ovarian cancer.

58. A method of enriching a population of genetically modified T cells expressing a FasBB fusion protein, the method comprising: contacting a culture of T cells with Fas ligand; and selecting viable T cells.

59. A method of killing a cancer cell presenting a p53 R175H mutant peptide on an HLA- A*02 molecule, the method comprising contacting the cancer cell with an engineered T cell expressing a heterologous T cell receptor (TCR) that binds the p53 R175H mutant peptide presented on an HLA-A*02 molecule.

60. A method of inhibiting or reducing tumor growth, wherein the tumor comprises cells presenting a p53 R175H mutant peptide on an HLA-A*02 molecule, the method comprising contacting the cancer tumor with engineered T cells each expressing a heterologous TCR that binds the p53 R175H mutant peptide presented on an HLA-A*02 molecule.

61. A method of treating a cancer in a subject, the method comprising: administering to the subject a pharmaceutically effective amount of engineered T cells each expressing a heterologous TCR that binds the p53 R175H mutant peptide presented on an HLA-A*02 molecule and a FasBB fusion protein.

62. The method of any one of claims 59-61, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 85% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

63. The method of any one of claims 59-61, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 90% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

64. The method of any one of claims 59-61, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence with at least 95% sequence identity to any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71- 77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

65. The method of any one of claims 59-61, wherein the TCR comprises: a TCR α chain variable (Vα) domain comprising an amino acid sequence of any one of SEQ ID NOs: 8, 28, 48, 68, 88, 108, 128, 148, 168, 188, 208, or 228; a TCR β chain variable (Vβ) domain comprising an amino acid sequence of any one of SEQ ID NOs: 18, 38, 58, 78, 98, 118, 138, 158, 178, 198, 218, or 238; or a TCRα FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region or a TCRβ FR1, CDR1, FR2, CDR2, FR3, CDR3, or FR4 region comprising an amino acid sequence of any one of SEQ ID NOs: 1-7, 11-17, 21-27, 31-37, 41-47, 51-57, 61-67, 71-77, 81-87, 91-97, 101-107, 111-117, 121-127, 131-137, 141-147, 151-157, 161-167, 171-177, 181-187, 191-197, 201-207, 211-217, 221-227, or 231-237.

66. The method of any one of claims 59-61, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 85% sequence identity to SEQ ID NO.

178.

67. The method of any one of claims 59-61, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 90% sequence identity to SEQ ID NO.178.

68. The method of any one of claims 59-61, wherein the TCR comprises a Vα comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO.168 and a Vβ comprising an amino acid sequence with at least 95% sequence identity to SEQ ID NO.

178.

69. The method of any one of claims 59-61, wherein the TCR comprises a Vα comprising an amino acid sequence of SEQ ID NO.168 and a Vβ comprising an amino acid sequence of SEQ ID NO.

178.

70. The method of any one of claims 59-69, wherein each engineered T cell co-expresses a CD8 co-receptor.

71. The method of any one of claims 59-70, wherein each engineered T cell comprises a chimeric fusion polypeptide comprising an IL7 receptor alpha intracellular domain.

72. The method of any one of claims 59-71, wherein each engineered T cell comprises a knockout of endogenous TRAC and / or TRBC.

73. The method of any one of claims 59-72, wherein the HLA*02 molecule is encoded by an HLA-A*02:01 allele.

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