Vaccine compositions and methods of use

Abstract

The present disclosure provides a therapy with vaccine compositions including multiepitopic polypeptides, recombinant nucleic acids encoding multiepitopic polypeptides and methods of use thereof. Also provided herein are T-cell receptors (TCRs) that can recognize one or more epitopes of the multiepitopic polypeptides. The therapy provided herein can comprise (i) a TCR, a recombinant nucleic acid encoding the TCR, or cells comprising the TCR or the recombinant nucleic acid encoding the TCR, and (ii) a vaccine composition described herein. The methods and compositions provided herein can be used for the treatment of cancer.

Description

VACCINE COMPOSITIONS AND METHODS OF USECROSS-REFERENCE

[0001] This application claims priority to U. S. Provisional Patent Application No. 63 / 769,412, filed on March 10, 2025, the contents of which are hereby incorporated by reference in their entirety.BACKGROUND

[0002] Cancer is a leading cause of death worldwide, accounting for nearly one in six deaths globally. While cell-based immunotherapies have led to advances in treatment options for cancer, they are often limited in their long-term efficacy. There is a need for methods and compositions to improve the efficacy of cell-based immunotherapy.SUMMARY

[0003] Recognized herein is a need to improve the efficacy of cell-based therapies to treat cancer. The methods and compositions provided herein can enhance the efficacy and persistence of cell-based immunotherapies.

[0004] Provided herein is a method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multi epitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope.

[0005] In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01.

[0006] In some embodiments, the epitope sequence presentable by HLA-B*08:01 comprises a sequence of any one of SEQ ID NOs: 6, 14 and 32.

[0007] In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01.

[0008] In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence of any one of SEQ ID NOs: 8, 22, and 26.

[0009] In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*01:01.

[0010] In some embodiments, the epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 28 or 30.

[0011] In some embodiments, the common C-allele epitope is presentable by an HLA-C.

[0012] In some embodiments, the HLA-C is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02.

[0013] In some embodiments, the common C-allele epitope comprises a sequence of SEQ ID NO: 24.

[0014] In some embodiments, the multiepitopic polypeptide further comprises a linker for analytics.

[0015] In some embodiments, the linker for analytics comprises a sequence of SEQ ID NO: 18.

[0016] In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the therapy is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0017] In some embodiments, the method further comprises administering to the subject a T-cell receptor (TCR) or a recombinant nucleic acid encoding the TCR.

[0018] In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence is separated by a linker.

[0019] In some embodiments, the first PRAME amino acid sequence is the first epitope sequence and / or the second PRAME amino acid sequence is the second epitope sequence.

[0020] In some embodiments, the first PRAME amino acid sequence consists of the first epitope sequence, and / or the second PRAME amino acid sequence consists of the second epitope sequence.

[0021] In some embodiments, the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length PRAME polypeptide.

[0022] In some embodiments, the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length PRAME polypeptide.

[0023] In some embodiments, the first PRAME amino acid sequence and the second PRAME amino acid sequence is separated by a linker.

[0024] In some embodiments, the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide.

[0025] In some embodiments, the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide.

[0026] In some embodiments, the multiepitopic polypeptide does not comprise more than 15 or more consecutive amino acids from the full-length PRAME polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length PRAME polypeptide.

[0027] In some embodiments, the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) the first or the second PRAME epitope sequence, and (ii) a human MHC encoded by an HLA allele.

[0028] Also provided herein is a method of treating a subject with a disease or condition comprising administering to the subject (a) a PRAME polypeptide, (b) a recombinant nucleic acid encoding the PRAME polypeptide, or (c) a cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide, wherein the PRAME polypeptide comprises a multiepitopic polypeptide that does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence,wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, wherein the subject has been previously administered a T-cell receptor (TCR) or a recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) the first or the second PRAME epitope sequence, and (ii) a human MHC encoded by an HLA allele.

[0029] Also provided herein is a method of treating a subject with a disease or condition comprising administering to the subject a T-cell receptor (TCR) or a recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) a PRAME epitope sequence, and (ii) a human MHC encoded by an ELLA allele, wherein the subject has been previously administered (a) a PRAME polypeptide, (b) a recombinant nucleic acid encoding the PRAME polypeptide, or (c) a cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide, wherein the PRAME polypeptide comprises a multiepitopic polypeptide that does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope.

[0030] Also provided herein is a method of treating a subject with a disease or condition comprising, (a) administering to the subject (i) a PRAME polypeptide, (ii) a recombinant nucleic acid encoding the PRAME polypeptide, or (iii) a cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide, wherein the PRAME polypeptide comprises a multiepitopic polypeptide that does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequenceand a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope; and (b) administering to the subject a TCR or a recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) the first or the second PRAME epitope sequence, and (ii) a human MHC encoded by an HLA allele.

[0031] In some embodiments, administering in (a) is performed concurrently with administering in (b).

[0032] In some embodiments, administering in (a) is prior to administering in (b).

[0033] In some embodiments, administering in (a) is subsequent to administering in (b).

[0034] In some embodiments, the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR.

[0035] In some embodiments, the TCR or the recombinant nucleic acid encoding the TCR is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide.

[0036] In some embodiments, the T-cell receptor (TCR) or the recombinant nucleic acid encoding the TCR is expressed by an immune cell.

[0037] In some embodiments, the TCR is a soluble TCR.

[0038] In some embodiments, the method further comprises administering two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs, and wherein the two or more different TCRs comprise a first TCR and a second TCR.

[0039] In some embodiments, the two or more different TCRs are expressed on surface of two different immune cells.

[0040] In some embodiments, the first TCR and the second TCR bind to different peptide: MHC complexes, each peptide: MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele.

[0041] In some embodiments, each of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope.

[0042] In some embodiments, the first PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02.

[0043] In some embodiments, the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, and the first PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02.

[0044] In some embodiments, the PRAME polypeptide further comprises one or more additional PRAME epitope sequences.

[0045] In some embodiments, the one or more additional PRAME epitope sequences comprise one or more epitope sequences selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02, and any combination thereof.

[0046] In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence of any one of SEQ ID NOs: 4, 10, 58, and 59.

[0047] In some embodiments, the epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

[0048] In some embodiments, the epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

[0049] In some embodiments, the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture.

[0050] In some embodiments, (a) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 16 and an MHC encoded by an HLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele; (b) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 16 and an MHC encoded by an HLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele; (c) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele; (d) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26 and an MHC encoded by an HLA-A*03:01 allele; (e) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele; (f) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele; (g) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encodedby an HLA-A*01:01 allele; (h) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele; or (i) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

[0051] In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

[0052] In some embodiments, the HLA allele is an HLA-A*02:01 allele.

[0053] In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

[0054] In some embodiments, the HLA allele is an HLA-B*07:02 allele.

[0055] In some embodiments, the PRAME epitope sequence comprises a sequence of any one of SEQ ID NOs: 4, 10, 58, and 59.

[0056] In some embodiments, the HLA allele is an HLA-A*24:02 allele.

[0057] In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32.

[0058] In some embodiments, the HLA allele is an HLA-B*08:01 allele.

[0059] In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26.

[0060] In some embodiments, the HLA allele is an HLA-A*03:01 allele.

[0061] In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30.

[0062] In some embodiments, the HLA allele is an HLA-A*01:01.

[0063] In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 24.

[0064] In some embodiments, the HLA allele is an HLA-C allele.

[0065] In some embodiments, the HLA-C allele is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02.

[0066] In some embodiments, the first and second PRAME epitope sequences are separated by one or more linker sequences.

[0067] In some embodiments, the one or more linker sequences are selected from the group consisting of SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 21, 23, 25, 27, 29, 31, 33, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, and any combination thereof.

[0068] In some embodiments, antigen presenting cells (APCs) of the subject administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide comprising the multiepitopic polypeptide present more of a PRAME epitope sequence as a peptide: MHC complex compared to the APCs of a subject administered a full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0069] In some embodiments, T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0070] In some embodiments, the first PRAME amino acid sequence is the first PRAME epitope sequence and / or the second PRAME amino acid sequence is the second PRAME epitope sequence.

[0071] In some embodiments, the first PRAME amino acid sequence consists of the first PRAME epitope sequence, and / or the second PRAME amino acid sequence consists of the second PRAME epitope sequence.

[0072] In some embodiments, the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length PRAME polypeptide.

[0073] In some embodiments, the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length PRAME polypeptide.

[0074] In some embodiments, the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide.

[0075] In some embodiments, the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide.

[0076] In some embodiments, the multiepitopic polypeptide does not comprise more than 15 or more consecutive amino acids from the full-length PRAME polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length PRAME polypeptide.

[0077] In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles.

[0078] In some embodiments, a first PRAME epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) binds to or is predicted to bind to a second HLA allele with a KDof more than 500 nM.

[0079] In some embodiments, the multiepitopic polypeptide comprises a first PRAME epitope sequence, operably linked to a second PRAME epitope sequence, operably linked to a third PRAME epitope sequence.

[0080] In some embodiments, the PRAME polypeptide further comprises one or more epitope sequences selected from the group consisting of an epitope presentable by HLA-A*02:01, an epitope presentable by HLA-B*07:02, and an epitope presentable by HLA-A*24:02.

[0081] In some embodiments, the epitope presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

[0082] In some embodiments, the epitope presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

[0083] In some embodiments, the epitope presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 4 or 10.

[0084] In some embodiments, the subject does not express an HLA allele that recognizes each PRAME epitope sequence of the multi epitopic polypeptide.

[0085] In some embodiments, the subject only expresses HLA alleles that recognize a subset of PRAME epitope sequences of the multiepitopic polypeptide.

[0086] In some embodiments, the multiepitopic polypeptide comprises, from N-terminus to C-terminus, a first epitope sequence presentable by HLA-A*24:02, a first epitope sequence presentable by HLA-B*08:01, a first epitope sequence presentable by HLA-A*03:01, a second epitope sequence presentable by HLA-A*24:02, a first epitope sequence presentable by HLA-B*07:02, a second epitope sequence presentable by HLA-B*08:01, a first epitope sequence presentable by HLA-A*02:01, a first epitope sequence presentable by HLA-A*01:01, a second epitope sequence presentable by HLA-A*03:01, a common C-allele epitope sequence, a third epitope sequence presentable by HLA-A*03:01, a second epitope sequence presentable by HLA-A*01:01, a third epitope sequence presentable by HLA-A*01:01, and a third epitope sequence presentable by HLA-B*08:01.

[0087] In some embodiments, the multiepitopic polypeptide comprises, from N-terminus to C-terminus, a first epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, an epitope sequence presentable by HLA-B*07:02, a common C-allele epitope sequence, a first epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, a second epitope sequence presentable by HLA-A*24:02, a first epitope sequence presentable by HLA-B*08:01, and a second epitope sequence presentable by HLA-B*08:01.

[0088] In some embodiments, each epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 4 or 10.

[0089] In some embodiments, each epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 6, 14, or 32.

[0090] In some embodiments, each epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 8, 22, or 26.

[0091] In some embodiments, each epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

[0092] In some embodiments, the epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

[0093] In some embodiments, each epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 20, 28, 30.

[0094] In some embodiments, the common C-allele epitope sequence comprises a sequence of SEQ ID NO: 24.

[0095] In some embodiments, the multiepitopic polypeptide comprises, at the N-terminal end, a Secretory (Sec) domain.

[0096] In some embodiments, the Sec domain comprises a sequence of SEQ ID NO: 1.

[0097] In some embodiments, the Sec domain is operably linked to the multiepitopic polypeptide via a linker.

[0098] In some embodiments, the linker comprises a sequence of SEQ ID NO: 2 or 37.

[0099] In some embodiments, the multiepitopic polypeptide comprises, at the C-terminal end, an MHC Class I Trafficking Signal (MITD) domain.

[0100] In some embodiments, the MITD domain comprises a sequence of SEQ ID NO: 34.

[0101] In some embodiments, the MITD domain is operably linked to the multiepitopic polypeptide via a linker.

[0102] In some embodiments, the linker comprises a sequence of SEQ ID NO: 2 or 37.

[0103] In some embodiments, each of the epitope sequences is flanked by one or more cleavable linker sequences.

[0104] In some embodiments, the one or more cleavable linker sequence is selected from the group consisting of SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 21, 23, 25, 27, 29, 31, 33, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, and any combination thereof.

[0105] In some embodiments, the multiepitopic polypeptide comprises a sequence having at least 80% identity to any one of SEQ ID NOs: 35, 36, and 38.

[0106] In some embodiments, the multiepitopic polypeptide comprises a sequence having at least 80% identity to SEQ ID NO: 55.

[0107] In some embodiments, the recombinant nucleic acid encoding the PRAME polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0108] In some embodiments, recombinant nucleic acid encoding the PRAME polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107,109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0109] In some embodiments, the recombinant nucleic acid encoding the PRAME polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0110] In some embodiments, the recombinant nucleic acid encoding the PRAME polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0111] In some embodiments, the recombinant nucleic acid encoding the multiepitopic polypeptide comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*07:02, a sequence encoding a second epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*02:01, a sequence encoding a first epitope sequence presentable by HLA-A*01:01, a sequence encoding a second epitope sequence presentable by HLA-A*03:01, a sequence encoding a common C-allele epitope sequence, a sequence encoding a third epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*01:01, a sequence encoding a third epitope sequence presentable by HLA-A*01:01, and a sequence encoding a third epitope sequence presentable by HLA-B*08:01.

[0112] In some embodiments, the recombinant nucleic acid encoding the multiepitopic polypeptide comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding an epitope sequence presentable by HLA-A*01:01, a sequence encoding an epitope sequence presentable by HLA-B*07:02, a sequence encoding a common C-allele epitope sequence, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding an epitope sequence presentable by HLA-A*02:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, and a sequence encoding a second epitope sequence presentable by HLA-B*08:01.

[0113] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 64, 70, 97, 103, 127, 133, 154, 176, 192, 197, 242, and 244.

[0114] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 66, 74, 92, 99, 107, 124, 129, 136, 151, 155, 160, 174, 179, 191, 194, 198, 207, 229, 231, and 233.

[0115] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 68, 82, 86, 101, 114, 118, 131, 142, 146, 156, 166, 169, 177, 184, 186, 195, 201, 203, and 218.

[0116] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 105, 134, 158, 105, 158, 222, and 240.

[0117] In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 76, 109, 138, 162, 181, 199, and 238.

[0118] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 84, 116, 144, 167, 202, and 224.

[0119] In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 24.

[0120] In some embodiments, the recombinant nucleic acid comprises, at the 5 ’end, a sequence encoding a Secretory (Sec) domain.

[0121] In some embodiments, the sequence encoding a Sec domain comprises a sequence of SEQ ID NO: 61.

[0122] In some embodiments, the sequence encoding the Sec domain is operably linked to the recombinant nucleic via a sequence encoding a linker.

[0123] In some embodiments, the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

[0124] In some embodiments, the recombinant nucleic acid comprises, at the 3 ’-end, a sequence encoding an MHC Class I Trafficking Signal (MITD) domain.

[0125] In some embodiments, the sequence encoding the MITD domain comprises a sequence of SEQ ID NO: 95 or 216.

[0126] In some embodiments, the sequence encoding the MITD domain is operably linked to the recombinant nucleic acid via a sequence encoding a linker.

[0127] In some embodiments, the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

[0128] In some embodiments, each of the sequences encoding an epitope sequence is flanked by a sequence encoding a cleavable linker.

[0129] In some embodiments, the sequence encoding the cleavable linker sequence is selected from the group consisting of SEQ ID NOs: 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159, 161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof.

[0130] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% identity to any one of SEQ ID NOs: 247-253, 255, 273, 274, and 293.

[0131] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% identity to SEQ ID NO: 254.

[0132] In some embodiments, the recombinant nucleic acid is codon-optimized.

[0133] In some embodiments, the recombinant nucleic acid is an RNA.

[0134] In some embodiments, the subject expresses more of the PRAME epitope when administered with the codon-optimized recombinant nucleic acid than administered with wildtype recombinant nucleic acid.

[0135] In some embodiments, the TCR comprises a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 262.

[0136] In some embodiments, the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 264 or 271.

[0137] In some embodiments, the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence set forth in SEQ ID NO: 260 and a complementarity determining region 2 (CDR2) having an amino acid sequence set forth in SEQ ID NO: 261.

[0138] In some embodiments, the TCR alpha chain construct comprises a CDR1, a CDR2, and a CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 257, the CDR2 has an amino acid sequence set forth in SEQ ID NO: 258, and the CDR3 has an amino acid sequence set forth in SEQ ID NO: 259.

[0139] In some embodiments, the TCR alpha chain construct comprises a variable region having an amino acid sequence having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 263 or 269.

[0140] IIn some embodiments, the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NO: 265, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 265, and (b) an alpha chain having an amino acid sequence set forth in SEQ ID NO: 294, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 294.

[0141] Also provided herein is a recombinant nucleic acid encoding a TCR comprising: (a) a TCR beta chain construct, and (b) a TCR alpha chain construct; wherein the TCR binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 6, 14 and 32, and a human MHC encoded by the HLA-B*08:01 allele; (ii) a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 8, 22, and 26, and a human MHC encoded by the HLA-A*03:01 allele; (iii) a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence according to SEQ ID NO: 28 or 30, and a human MHC encoded by the HLA-A*01:01 allele; or (iv) a PRAME epitope sequence havingat least 7 consecutive amino acids of a sequence according to SEQ ID NO: 24, and a human MHC encoded by an HLA-C allele.

[0142] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 6, 14 and 32, and a human MHC encoded by the HLA-B*08:01 allele.

[0143] In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to any one of SEQ ID NOs: 6, 14 and 32.

[0144] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 8, 22, and 26, and a human MHC encoded by the HLA-A*03:01 allele.

[0145] In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to any one of SEQ ID NOs: 8, 22, and 26.

[0146] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence according to SEQ ID NO: 28 or 30, and a human MHC encoded by the HLA-A*01:01 allele.

[0147] In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NOs: 28 or 30.

[0148] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of SEQ ID NO: 24, and a human MHC encoded by the HLA-C allele.

[0149] In some embodiments, the HLA-C allele is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02.

[0150] In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 24.

[0151] Also provided herein is a cell comprising the recombinant nucleic acid of any one of the foregoing embodiments.

[0152] In some embodiments, the cell is a T cell.

[0153] In some embodiments, upon binding of the TCR to the peptide: MHC complex, the cell produces a proinflammatory cytokine.

[0154] In some embodiments, the proinflammatory cytokine is IFN-y, IL-2, TNF-a, IL-6, or IL-

[0155] In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cells is increased by 25%, 50%, 100%, 150%, 200%, or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.

[0156] Also provided herein is a recombinant nucleic acid encoding a multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope.

[0157] In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0158] In some embodiments, the first PRAME amino acid sequence is the first epitope sequence and / or the second PRAME amino acid sequence is the second epitope sequence.

[0159] In some embodiments, the first PRAME amino acid sequence consists of the first epitope sequence, and / or the second PRAME amino acid sequence consists of the second epitope sequence.

[0160] In some embodiments, the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length PRAME polypeptide.

[0161] In some embodiments, the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length PRAME polypeptide.

[0162] In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence is separated by a linker.

[0163] In some embodiments, the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide.

[0164] In some embodiments, the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide.

[0165] In some embodiments, the multi epitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length PRAME polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length PRAME polypeptide.

[0166] In some embodiments, the multiepitopic polypeptide further comprises a Secretory (Sec) sequence at the N-terminus of the multiepitopic polypeptide.

[0167] In some embodiments, the Sec sequence comprises a sequence of SEQ ID NO: 1.

[0168] In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker.

[0169] In some embodiments, the linker comprises a sequence of SEQ ID NO: 2 or 37.

[0170] In some embodiments, the multiepitopic polypeptide further comprises an MHC class I trafficking signal (MITD) sequence at the C-terminus of the multiepitopic polypeptide.

[0171] In some embodiments, the MITD sequence comprises a sequence of SEQ ID NO: 34.

[0172] In some embodiments, the multiepitopic polypeptide is operably linked to the MITD sequence via a linker.

[0173] In some embodiments, the linker comprises a sequence of SEQ ID NO: 2 or 37.

[0174] In some embodiments, the multiepitopic polypeptide comprises at least 3, 4, 5, or more different PRAME epitope sequences.

[0175] In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles.

[0176] In some embodiments, a first PRAME epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) binds to or is predicted to bind to a second HLA allele with a KDof more than 500 nM.

[0177] In some embodiments, each of the sequences encoding the PRAME epitope sequences is flanked by one or more sequences encoding a cleavable linker sequence.

[0178] In some embodiments, the one or more sequences encoding a cleavable linker sequence is selected from the group consisting of SEQ ID NOs: 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159, 161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof.

[0179] In some embodiments, the multiepitopic polypeptide comprises a first PRAME epitope sequence, operably linked to a second PRAME epitope sequence, operably linked to a third PRAME epitope sequence.

[0180] In some embodiments, the recombinant nucleic acid comprises one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0181] In some embodiments, the recombinant nucleic acid comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0182] In some embodiments, the recombinant nucleic acid comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155,156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0183] In some embodiments, the recombinant nucleic acid comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0184] In some embodiments, the recombinant nucleic acid comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*07:02, a sequence encoding a second epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*02:01, a sequence encoding a first epitope sequence presentable by HLA-A*01:01, a sequence encoding a second epitope sequence presentable by HLA-A*03:01, a sequence encoding a common C-allele epitope sequence, a sequence encoding a third epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*01:01, a sequence encoding a third epitope sequence presentable by HLA-A*01:01, and a sequence encoding a third epitope sequence presentable by HLA-B*08:01.

[0185] In some embodiments, the recombinant nucleic acid comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding an epitope sequence presentable by HLA-A*01:01, a sequence encoding an epitope sequence presentable by HLA-B*07:02, a sequence encoding a common C-allele epitope sequence, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding an epitope sequence presentable by HLA-A*02:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, and a sequence encoding a second epitope sequence presentable by HLA-B*08:01.

[0186] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence selected from the group consisting of SEQ ID NOs: 64, 70, 97, 103, 127, 133, 154, 176, 192, 197, 242, and 244.

[0187] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 66, 74, 92, 99, 107, 124, 129, 136, 151, 155, 160, 174, 179, 191, 194, 198, 207, 229, 231, and 233.

[0188] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 68, 82, 86, 101, 114, 118, 131, 142, 146, 156, 166, 169, 177, 184, 186, 195, 201, 203, and 218.

[0189] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence selected from the group consisting of SEQ ID NOs: 105, 134, 158, 105, 158, 222, and 240.

[0190] In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 76, 109, 138, 162, 181, 199, and 238.

[0191] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 80, 88, 90, 112, 120, 122, 140, 148, 149, 164, 171, 172, 188, 189, 200, 204, 206, 220, 235, and 237.

[0192] In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 84, 116, 144, 167, 202, and 224.

[0193] In some embodiments, the recombinant nucleic acid comprises, at the 5 ’end, a sequence encoding a Secretory (Sec) domain.

[0194] In some embodiments, the sequence encoding a Sec domain comprises a sequence of SEQ ID NO: 61.

[0195] In some embodiments, the sequence encoding the Sec domain is operably linked to the recombinant nucleic via a sequence encoding a linker.

[0196] In some embodiments, the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

[0197] In some embodiments, the recombinant nucleic acid comprises, at the 3 ’-end, a sequence encoding an MHC Class I Trafficking Signal (MITD) domain.

[0198] In some embodiments, the sequence encoding the MITD domain comprises a sequence of SEQ ID NO: 95 or 216.

[0199] In some embodiments, the sequence encoding the MITD domain is operably linked to the recombinant nucleic acid via a sequence encoding a linker.

[0200] In some embodiments, the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

[0201] In some embodiments, each of the sequences encoding an epitope sequence is flanked by one or more sequences encoding a cleavable linker.

[0202] In some embodiments, the one or more sequences encoding the cleavable linker is selected from the group consisting of SEQ ID NOs: 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159, 161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof.

[0203] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% identity to any one of SEQ ID NOs: 247-253, 255, 273, 274, and 293.

[0204] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 80% identity to SEQ ID NO: 254.

[0205] Also provided herein is a recombinant nucleic acid having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 245-253, 254-256, 273, 274, and 293.

[0206] Also provided herein is a recombinant polypeptide having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 35, 36, 38, 55, and 60.

[0207] Also provided herein is a polypeptide encoded by the recombinant nucleic acid of any one of the foregoing embodiments.

[0208] Also provided herein is a pharmaceutical composition comprising the recombinant nucleic acid of any one of the foregoing embodiments or the polypeptide of any one of the foregoing embodiments, and a pharmaceutically acceptable carrier.

[0209] Also provided herein is the recombinant nucleic acid of any one of the foregoing embodiments, the polypeptide of any one of the foregoing embodiments, or the pharmaceutical composition of any one of the foregoing embodiments for use in therapy.

[0210] Also provided herein is use of the recombinant nucleic acid of any one of the foregoing embodiments, the polypeptide of any one of the foregoing embodiments, or the pharmaceutical composition of any one of the foregoing embodiments, in the manufacture of a medicament for the treatment of cancer in a subject in need thereof.BRIEF DESCRIPTION OF THE DRAWINGS

[0211] The novel features of the invention are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present invention will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the invention are utilized, and the accompanying drawings (also “Figure” and “FIG.” herein), of which:

[0212] FIG. 1A depicts results of an activation assay measuring IFNy production by T cells recognizing target cells expressing PRAME epitope SLLQHLIGL (SEQ ID NO: 16) and HLA-A*02:01.

[0213] FIG. 1B depicts results of an activation assay measuring IFNy production by T cells recognizing target cells expressing PRAME epitope SPSVSQLSVL (SEQ ID NO: 12) and HLA-B*07:02.

[0214] FIG.2 depicts results measuring expansion of T cells expressing a PRAME-specific TCR in mice treated with an mRNA PRAME vaccine.

[0215] FIGs.3A-3B depict results measuring IFNy production by T cells recognizing target cells expressing PRAME on HLA-A*02:01. FIG. 3A depicts results from one human donor. FIG. 3B depicts results from another human donor.DETAILED DESCRIPTIONDefinitions

[0216] To facilitate an understanding of the present disclosure, a number of terms and phrases are defined below.

[0217] An antigen is a foreign substance to the body that induces an immune response. A “neoantigen” refers to a class of tumor antigens which arise from tumor-specific changes in proteins. Neoantigens encompass, but are not limited to, tumor antigens which arise from, forexample, a substitution in a protein sequence, a frame shift mutation, a fusion polypeptide, an inframe deletion, an insertion, and expression of an endogenous retroviral polypeptide.

[0218] A “neoepitope” refers to an epitope that is not present in a reference, such as a non-diseased cell, e.g., a non-cancerous cell or a germline cell, but is found in a diseased cell, e.g., a cancer cell. This includes situations where a corresponding epitope is found in a normal non-diseased cell or a germline cell but, due to one or more mutations in a diseased cell, e.g., a cancer cell, the sequence of the epitope is changed so as to result in the neoepitope.

[0219] A “mutation” refers to a change of or a difference in a nucleic acid sequence (e.g., a nucleotide substitution, addition or deletion) compared to a reference nucleic acid. A “somatic mutation” can occur in any of the cells of the body except the germ cells (sperm and egg) and are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. In some embodiments, a mutation is a non- synonymous mutation. A “non-synonymous mutation” refers to a mutation, for (e.g., a nucleotide substitution), which does result in an amino acid change such as an amino acid substitution in the translation product. A “frameshift” occurs when a mutation disrupts the normal phase of a gene’s codon periodicity (also known as “reading frame”), resulting in translation of a non-native protein sequence. It is possible for different mutations in a gene to achieve the same altered reading frame.

[0220] “Antigen processing” or “processing” refers to the degradation of a polypeptide or antigen into procession products, which are fragments of said polypeptide or antigen (e.g., the degradation of a polypeptide into peptides) and the association of one or more of these fragments (e.g., via binding) with MHC molecules for presentation by cells, for example, antigen presenting cells, to specific T cells.

[0221] An “antigen presenting cell” (APC) refers to a cell which presents peptide fragments of protein antigens in association with MHC molecules on its cell surface. The term includes professional antigen presenting cells (e.g., B lymphocytes, monocytes, dendritic cells, Langerhans cells) as well as other antigen presenting cells (e.g., keratinocytes, endothelial cells, astrocytes, fibroblasts, oligodendrocytes). In some cases, the APC can be a cancer cell.

[0222] The term “affinity” refers to a measure of the strength of binding between two members of a binding pair (e.g., a human leukocyte antigen (HLA)-binding peptide and a class I or II HLA, or a peptide-HLA complex and a T cell receptor (TCR)). KD refers to the dissociation constant between two members of a binding pair and has units of molarity. KA refers to the affinity constantbetween two members of a binding pair is the inverse of the dissociation constant. Affinity may be determined experimentally, for example by surface plasmon resonance (SPR) using commercially available Biacore SPR units. Koffrefers to the off-rate constant of two members of a binding pair, (e.g., the off-rate constant of an HLA-binding peptide and a class I or II HLA, or a peptide-HLA complex and a TCR). Konrefers to the on-rate constant of two members of a binding pair, (e.g., the on-rate constant of an HLA-binding peptide and a class I or II HLA, or a peptide-HLA complex and a TCR).

[0223] Throughout this disclosure, “binding data” results may be expressed in terms of an “IC50.” Affinity may also be expressed as the inhibitory concentration 50 (IC50), or the concentration at which 50% of a first member of a binding pair (e.g., a peptide) is displaced. Likewise, In(ICso) refers to the natural log of the IC50. For example, an IC50 may be the concentration of a tested peptide in a binding assay at which 50% inhibition of binding of a labeled reference peptide is observed. Given the conditions in which the assays are run (e.g., limiting HLA protein concentrations and / or labeled reference peptide concentrations), these values can approximate KD values. Assays for determining binding are well known in the art and are described in detail, for example, in PCT publications WO 94 / 20127 and WO 94 / 03205, and other publications such Sidney etal., Current Protocols in Immunology 18.3.1 (1998); Sidney, etal., J. Immunol. 154:247 (1995); and Sette, et al., Mol. Immunol. 31:813 (1994). Alternatively, binding can be expressed relative to binding by a reference standard peptide. Binding can also be determined using other assay systems including those using: live cells (e.g., Ceppellini et al., Nature 339:392 (1989); Christnick et al., Nature 352:67 (1991); Busch et al., Int. Immunol. 2:443 (1990); Hill et al., J. Immunol. 147:189 (1991); del Guercio etal., J. Immunol. 154:685 (1995)), cell free systems using detergent lysates (e.g., Cerundolo et al., J. Immunol. 21:2069 (1991)), immobilized purified MHC (e.g., Hill et al., J. Immunol. 152, 2890 (1994); Marshall et al., J. Immunol. 152:4946 (1994)), ELISA systems (e.g., Reay et al., EMBO J. 11:2829 (1992)), surface plasmon resonance (e.g., Khilko et al., J. Biol. Chem. 268:15425 (1993)); high flux soluble phase assays (Hammer et al., J. Exp. Med. 180:2353 (1994)), and measurement of class I MHC stabilization or assembly (e.g., Ljunggren et al., Nature 346:476 (1990); Schumacher et al., Cell 62:563 (1990); Townsend et al., Cell 62:285 (1990); Parker et al., J. Immunol. 149:1896 (1992)).

[0224] The term “derived” when used to discuss an epitope is a synonym for “prepared.” A derived epitope can be isolated from a natural source, or it can be synthesized according to standardprotocols in the art. Synthetic epitopes can comprise artificial amino acid residues “amino acid mimetics,” such as D isomers of natural occurring L amino acid residues or non-natural amino acid residues such as cyclohexylalanine. A derived or prepared epitope can be an analog of a native epitope. The term “derived from” refers to the origin or source, and may include naturally occurring, recombinant, unpurified, purified or differentiated molecules or cells. For example, an expanded or induced antigen specific T cell may be derived from a T cell. For example, an expanded or induced antigen specific T cell may be derived from an antigen specific T cell in a biological sample. For example, a matured APC (e.g., a professional APC) may be derived from a non-matured APC (e.g., an immature APC). For example, an APC may be derived from a monocyte (e.g., a CD14+monocyte). For example, a dendritic cell may be derived from a monocyte (e.g., a CD14+monocyte). For example, an APC may be derived from a bone marrow cell.

[0225] An “epitope” is the collective features of a molecule (e.g., a peptide’s charge and primary, secondary and tertiary structure) that together form a site recognized by another molecule (e.g., an immunoglobulin, T cell receptor, HLA molecule, or chimeric antigen receptor). For example, an epitope can be a set of amino acid residues involved in recognition by a particular immunoglobulin; a Major Histocompatibility Complex (MHC) receptor; or in the context of T cells, those residues recognized by a T cell receptor protein and / or a chimeric antigen receptor. Epitopes can be prepared by isolation from a natural source, or they can be synthesized according to standard protocols in the art. Synthetic epitopes can comprise artificial amino acid residues, amino acid mimetics, (such as D isomers of naturally-occurring L amino acid residues or non-naturally-occurring amino acid residues). Throughout this disclosure, epitopes may be referred to in some cases as peptides or peptide epitopes. In certain embodiments, there is a limitation on the length of a peptide of the present disclosure. The embodiment that is length-limited occurs when the protein or peptide comprising an epitope described herein comprises a region (i.e., a contiguous series of amino acid residues) having 100% sequence identity with a native sequence. In order to avoid the definition of epitope from reading, e.g., on whole natural molecules, there is a limitation on the length of any region that has 100% sequence identity with a native peptide sequence. Thus, for a peptide comprising an epitope described herein and a region with 100% sequence identity with a native peptide sequence, the region with 100% sequence identity to a native sequence generally has a length of: less than or equal to 600 amino acid residues, less than or equal to 500 amino acid residues, less than or equal to 400 amino acid residues, less than or equal to 250 aminoacid residues, less than or equal to 100 amino acid residues, less than or equal to 85 amino acid residues, less than or equal to 75 amino acid residues, less than or equal to 65 amino acid residues, and less than or equal to 50 amino acid residues. In certain embodiments, an “epitope” described herein is comprised by a peptide having a region with less than 51 amino acid residues that has 100% sequence identity to a native peptide sequence, in any increment down to 5 amino acid residues; for example 50, 49, 48, 47, 46, 45, 44, 43, 42, 41, 40, 39, 38, 37, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2 or 1 amino acid residues.

[0226] A “T cell epitope” refers to a peptide sequence bound by an MHC molecule in the form of a peptide-MHC (pMHC) complex. A peptide-MHC complex can be recognized and bound by a TCR of a T cell (e.g., a cytotoxic T-lymphocyte or a T-helper cell).

[0227] A “T cell” includes CD4+T cells and CD8+T cells. The term T cell also includes both T helper 1 type T cells and T helper 2 type T cells. T cells may be generated by the method described in the application, for a clinical application. T cells or adoptive T cells referred to here, such as for a clinical application are cells isolated from a biological source, manipulated and cultured ex vivo and prepared into a drug candidate for a specific therapy such as a cancer, e.g., melanoma. When drug candidate cells pass specific qualitative and quantitative criteria for fitness for a clinical application, the drug candidate may be designated a drug product. In some cases, a drug product is selected from a number of drug candidates. In the context of this application, a drug product is a T cell, more specifically, a population of T cells, or more specifically a population of T cells with heterogeneous characteristics and subtypes. For example, a drug product, as disclosed herein may have a population of T cells comprising CD8+ T cells, CD4+ T cells, with cells at least above a certain exhibiting antigen specificity, a certain percentage of each exhibiting a memory phenotype, among others.

[0228] An “immune cell” refers to a cell that plays a role in the immune response. Immune cells are of hematopoietic origin, and include lymphocytes, such as B cells and T cells; natural killer cells; myeloid cells, such as monocytes, macrophages, eosinophils, mast cells, basophils, and granulocytes.

[0229] An “immunogenic” peptide or an “immunogenic” epitope or an “immunogenic” peptide epitope is a peptide that binds to an HLA molecule and induces a cell-mediated or humoral response, for example, a cytotoxic T lymphocyte (CTL) response, a helper T lymphocyte (HTL)response and / or a B lymphocyte response. Immunogenic peptides described herein are capable of binding to an HLA molecule and thereafter induce a cell-mediated or humoral response (e.g., a CTL (cytotoxic) response, or a HTL response) to the peptide.

[0230] A “protective immune response” or “therapeutic immune response” refers to a CTL and / or an HTL response to an antigen derived from a pathogenic antigen (e.g., a tumor antigen), which in some way prevents or at least partially arrests disease symptoms, side effects or progression. The immune response can also include an antibody response which has been facilitated by the stimulation of helper T cells.

[0231] A “T cell receptor” (“TCR”) refers to a molecule, whether natural or partly or wholly synthetically produced, found on the surface of T lymphocytes (T cells) that recognizes an antigen bound to a major histocompatibility complex (MHC) molecule. The ability of a T cells to recognize an antigen associated with various diseases (e.g., cancers) or infectious organisms is conferred by its TCR, which is made up of both an alpha (a) chain and a beta (β) chain or a gamma (γ) and a delta (δ) chain. The proteins which make up these chains are encoded by DNA, which employs a unique mechanism for generating the tremendous diversity of the TCR. This multi-subunit immune recognition receptor associates with the CD3 complex and binds peptides presented by the MHC class I and II proteins on the surface of antigen-presenting cells (APCs). Binding of a TCR to a peptide on an APC is a central event in T cell activation.

[0232] As used herein, a “chimeric antigen receptor” or “CAR” refers to an antigen binding protein in that includes an immunoglobulin antigen binding domain (e.g., an immunoglobulin variable domain) and a T cell receptor (TCR) constant domain. As used herein, a “constant domain” of a TCR polypeptide includes a membrane-proximal TCR constant domain, a TCR transmembrane domain and / or a TCR cytoplasmic domain, or fragments thereof. For example, in some embodiments, a CAR is a monomer that includes a polypeptide comprising an immunoglobulin heavy chain variable domain linked to a TCR0 constant domain. In some embodiments, the CAR is a dimer that includes a first polypeptide comprising an immunoglobulin heavy or light chain variable domain linked to a TCRa or TCR0constant domain and a second polypeptide comprising an immunoglobulin heavy or light chain variable domain (e.g., a K or A. variable domain) linked to a TCR0 or TCRa constant domain.

[0233] “Major Histocompatibility Complex” or “MHC” is a cluster of genes that plays a role in control of the cellular interactions responsible for physiologic immune responses. The terms“major histocompatibility complex” and the abbreviation “MHC” can include any class of MHC molecule, such as MHC class I and MHC class II molecules, and relate to a complex of genes which occurs in all vertebrates. In humans, the MHC complex is also known as the human leukocyte antigen (HLA) complex. Thus, a “Human Leukocyte Antigen” or “HLA” refers to a human Major Histocompatibility Complex (MHC) protein (see, e.g., Stites, et al., Immunology, 8THEd., Lange Publishing, Los Altos, Calif. (1994). For a detailed description of the MHC and HLA complexes, see, Paul, Fundamental Immunology, 3rdEd., Raven Press, New York (1993).

[0234] The major histocompatibility complex in the genome comprises the genetic region whose gene products expressed on the cell surface are important for binding and presenting endogenous and / or foreign antigens and thus for regulating immunological processes. MHC proteins or molecules are important for signaling between lymphocytes and antigen presenting cells or diseased cells in immune reactions. MHC proteins or molecules bind peptides and present them for recognition by T-cell receptors. The proteins encoded by the MHC can be expressed on the surface of cells, and display both self-antigens (peptide fragments from the cell itself) and nonself-antigens (e.g., fragments of invading microorganisms) to a T-cell. MHC binding peptides can result from the proteolytic cleavage of protein antigens and represent potential lymphocyte epitopes, (e.g., T cell epitope and B cell epitope). MHCs can transport the peptides to the cell surface and present them there to specific cells, such as cytotoxic T-lymphocytes, T-helper cells, or B cells. The MHC region can be divided into three subgroups, class I, class II, and class III. MHC class I proteins can contain an a-chain and P2-microglobulin (not part of the MHC encoded by chromosome 15). They can present antigen fragments to cytotoxic T-cells. MHC class II proteins can contain a- and P-chains and they can present antigen fragments to T-helper cells. MHC class III region can encode for other immune components, such as complement components and cytokines. The MHC can be both polygenic (there are several MHC class I and MHC class II genes) and polymorphic (there are multiple alleles of each gene).

[0235] A “receptor” refers to a biological molecule or a molecule grouping capable of binding a ligand. A receptor may serve, to transmit information in a cell, a cell formation or an organism. A receptor comprises at least one receptor unit, for example, where each receptor unit may consist of a protein molecule. A receptor has a structure which complements that of a ligand and may complex the ligand as a binding partner. The information is transmitted in particular by conformational changes of the receptor following complexation of the ligand on the surface of acell. In some embodiments, a receptor is to be understood as meaning in particular proteins of MHC classes I and II capable of forming a receptor / ligand complex with a ligand, in particular a peptide or peptide fragment of suitable length. A “ligand” refers to a molecule which has a structure complementary to that of a receptor and is capable of forming a complex with this receptor. In some embodiments, a ligand is to be understood as meaning a peptide or peptide fragment which has a suitable length and suitable binding motifs in its amino acid sequence, so that the peptide or peptide fragment is capable of forming a complex with MHC proteins such as MHC class I or MHC class II proteins. In some embodiments, a “receptor / ligand complex” is also to be understood as meaning a “receptor / peptide complex” or “receptor / peptide fragment complex”, including a peptide- or peptide fragment-presenting MHC molecule such as MHC class I or MHC class II molecules.

[0236] A “native” or a “wild type” sequence refers to a sequence found in nature. The term “naturally occurring” as used herein refers to the fact that an object can be found in nature. For example, a peptide or nucleic acid that is present in an organism (including viruses) and can be isolated from a source in nature and which has not been intentionally modified by man in the laboratory is naturally occurring.

[0237] The terms “peptide” and “peptide epitope” are used interchangeably with “oligopeptide” in the present specification to designate a series of residues connected one to the other, typically by peptide bonds between the a-amino and carboxyl groups of adjacent amino acid residues. A “synthetic peptide” refers to a peptide that is obtained from a non-natural source, e.g., is manmade. Such peptides can be produced using such methods as chemical synthesis or recombinant DNA technology. “Synthetic peptides” include “fusion proteins.”

[0238] The term “motif’ refers to a pattern of residues in an amino acid sequence of defined length, for example, a peptide of less than about 15 amino acid residues in length, or less than about 13 amino acid residues in length, for example, from about 8 to about 13 amino acid residues (e.g., 8, 9, 10, 11, 12, or 13) for a class I HLA motif and from about 6 to about 25 amino acid residues (e.g., 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25) for a class II HLA motif, which is recognized by a particular HLA molecule. Motifs are typically different for each HLA protein encoded by a given human HLA allele. These motifs differ in their pattern of the primary and secondary anchor residues. In some embodiments, an MHC class I motif identifies a peptide of 7, 89, 10, 11, 12 or 13 amino acid residues in length. In some embodiments, an MHCclass II motif identifies a peptide of 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25 or 26 amino acid residues in length. A “cross-reactive binding” peptide refers to a peptide that binds to more than one member of a class of a binding pair members (e.g., a peptide bound by both a class I HLA molecule and a class II HLA molecule).

[0239] The term “residue” refers to an amino acid residue or amino acid mimetic residue incorporated into a peptide or protein by an amide bond or amide bond mimetic, or that is encoded by a nucleic acid (DNA or RNA). The nomenclature used to describe peptides or proteins follows the conventional practice. The amino group is presented to the left (the amino- or N-terminus) and the carboxyl group to the right (the carboxy- or C-terminus) of each amino acid residue. When amino acid residue positions are referred to in a peptide epitope, they are numbered in an amino to carboxyl direction with the first position being the residue located at the amino terminal end of the epitope, or the peptide or protein of which it can be a part. In the formulae representing selected specific embodiments of the present disclosure, the amino- and carboxyl-terminal groups, although not specifically shown, are in the form they can assume at physiologic pH values, unless otherwise specified. In the amino acid structure formulae, each residue is generally represented by standard three letter or single letter designations. The L-form of an amino acid residue is represented by a capital single letter or a capital first letter of a three-letter symbol, and the D-form for those amino acid residues having D-forms is represented by a lower case single letter or a lower case three letter symbol. However, when three letter symbols or full names are used without capitals, they can refer to L amino acid residues. Glycine has no asymmetric carbon atom and is simply referred to as “Gly” or “G”. The amino acid sequences of peptides set forth herein are generally designated using the standard single letter symbol. (A, Alanine; C, Cysteine; D, Aspartic Acid; E, Glutamic Acid; F, Phenylalanine; G, Glycine; H, Histidine; I, Isoleucine; K, Lysine; L, Leucine; M, Methionine; N, Asparagine; P, Proline; Q, Glutamine; R, Arginine; S, Serine; T, Threonine; V, Valine; W, Tryptophan; and Y, Tyrosine.)

[0240] A “conservative amino acid substitution” is one in which one amino acid residue is replaced with another amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art, including basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine,tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine). For example, substitution of a phenylalanine for a tyrosine is a conservative substitution. Methods of identifying nucleotide and amino acid conservative substitutions which do not eliminate peptide function are well-known in the art.

[0241] “Pharmaceutically acceptable” refers to a generally non-toxic, inert, and / or physiologically compatible composition or component of a composition. A “pharmaceutical excipient” or “excipient” comprises a material such as an adjuvant, a carrier, pH-adjusting and buffering agents, tonicity adjusting agents, wetting agents, preservatives, and the like. A “pharmaceutical excipient” is an excipient which is pharmaceutically acceptable.

[0242] According to the present disclosure, the term “vaccine” relates to a pharmaceutical preparation (pharmaceutical composition) or product that upon administration induces an immune response, for example, a cellular or humoral immune response, which recognizes and attacks a pathogen or a diseased cell such as a cancer cell. A vaccine may be used for the prevention or treatment of a disease. The term “individualized cancer vaccine” or “personalized cancer vaccine” “personal cancer vaccine” concerns a particular cancer patient and means that a cancer vaccine is adapted to the needs or special circumstances of an individual cancer patient.

[0243] The terms “polynucleotide” and “nucleic acid” are used interchangeably herein and refer to polymers of nucleotides of any length, and include DNA and RNA, for example, mRNA. The nucleotides can be deoxyribonucleotides, ribonucleotides, modified nucleotides or bases, and / or their analogs, or any substrate that can be incorporated into a polymer by DNA or RNA polymerase. In some embodiments, the polynucleotide and nucleic acid can be in vitro transcribed mRNA. In some embodiments, the polynucleotide that is administered using the methods of the present disclosure is mRNA.

[0244] The terms “isolated” or “biologically pure” refer to material which is substantially or essentially free from components which normally accompany the material as it is found in its native state. Thus, isolated peptides described herein do not contain some or all of the materials normally associated with the peptides in their in situ environment. For example, an “isolated” epitope can be an epitope that does not include the whole sequence of the protein from which the epitope was derived. For example, a naturally-occurring polynucleotide or peptide present in a living animal is not isolated, but the same polynucleotide or peptide, separated from some or allof the coexisting materials in the natural system, is isolated. Such a polynucleotide could be part of a vector, and / or such a polynucleotide or peptide could be part of a composition, and still be “isolated” in that such vector or composition is not part of its natural environment. Isolated RNA molecules include in vivo or in vitro RNA transcripts of the DNA molecules described herein, and further include such molecules produced synthetically. In some embodiments, a polypeptide, antibody, polynucleotide, vector, cell, or composition which is isolated is substantially pure. The term “substantially pure” as used herein refers to material which is at least 50% pure (i.e., free from contaminants), at least 90% pure, at least 95% pure, at least 98% pure, or at least 99% pure.

[0245] The terms “identical” or percent “identity” in the context of two or more nucleic acids or polypeptides, refer to two or more sequences or subsequences that are the same or have a specified percentage of nucleotides or amino acid residues that are the same, when compared and aligned (introducing gaps, if necessary) for maximum correspondence, not considering any conservative amino acid substitutions as part of the sequence identity. The percent identity can be measured using sequence comparison software or algorithms or by visual inspection. Various algorithms and software that can be used to obtain alignments of amino acid or nucleotide sequences are well-known in the art. These include, but are not limited to, BLAST, ALIGN, Megalign, BestFit, GCG Wisconsin Package, and variations thereof. In some embodiments, two nucleic acids or polypeptides described herein are substantially identical, meaning they have at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, and in some embodiments at least 95%, 96%, 97%, 98%, 99% nucleotide or amino acid residue identity, when compared and aligned for maximum correspondence, as measured using a sequence comparison algorithm or by visual inspection. In some embodiments, identity exists over a region of the sequences that is at least about 10, at least about 20, at least about 40-60 residues, at least about 60-80 residues in length or any integral value there between. In some embodiments, identity exists over a longer region than 60-80 residues, such as at least about 80-100 residues, and in some embodiments the sequences are substantially identical over the full length of the sequences being compared, such as an amino acid sequence of a peptide or a coding region of a nucleotide sequence.

[0246] The term “subject” refers to any animal (e.g., a mammal), including, but not limited to, humans, non-human primates, canines, felines, rodents, and the like, which is to be the recipient of a particular treatment. Typically, the terms “subject” and “patient” are used interchangeably herein in reference to a human subject.

[0247] The terms “effective amount” or “therapeutically effective amount” or “therapeutic effect” refer to an amount of a therapeutic effective to “treat” a disease or disorder in a subject or mammal. The therapeutically effective amount of a drug has a therapeutic effect and as such can prevent the development of a disease or disorder; slow down the development of a disease or disorder; slow down the progression of a disease or disorder; relieve to some extent one or more of the symptoms associated with a disease or disorder; reduce morbidity and mortality; improve quality of life; or a combination of such effects.

[0248] The terms “treating” or “treatment” or “to treat” or “alleviating” or “to alleviate” refer to both (1) therapeutic measures that cure, slow down, lessen symptoms of, and / or halt progression of a diagnosed pathologic condition or disorder and (2) prophylactic or preventative measures that prevent or slow the development of a targeted pathologic condition or disorder. Thus, those in need of treatment include those already with the disorder; those prone to have the disorder; and those in whom the disorder is to be prevented.

[0249] The term “depleted” when used to describe a cell sample (e.g., a peripheral blood mononuclear cell (PBMC) sample) refers to a cell sample in which a subpopulation of cells has been removed or depleted. For example, an immune cell sample depleted of CD25 expressing cells refers to an immune cell sample in which CD25 expressing cells have been removed or depleted. For example, one or more binding agents can be used to remove or deplete one or more cells or cell types from a sample. For example, CD14+cells can be depleted or removed from a PBMC sample, such as by using an antibody that binds to CD14.

[0250] The “stimulation” refers to a response induced by binding of a stimulatory molecule with its cognate ligand thereby mediating a signal transduction event. For example, stimulation of a T cell can refer to binding of a TCR of a T cell to a peptide-MHC complex. For example, stimulation of a T cell can refer to a step within protocol 1 or protocol 2 in which PBMCs are cultured together with peptide loaded APCs.

[0251] The term “enriched” refers to a composition or fraction wherein an object species has been partially purified such that the concentration of the object species is substantially higher than the naturally occurring level of the species in a finished product without enrichment. The term “induced cell” refers to a cell that has been treated with an inducing compound, cell, or population of cells that affects the cell’s protein expression, gene expression, differentiation status, shape, morphology, viability, and the like.

[0252] A “reference” can be used to correlate and / or compare the results obtained in the methods of the present disclosure from a diseased specimen. Typically, a “reference” may be obtained on the basis of one or more normal specimens, in particular specimens which are not affected by a disease, either obtained from an individual or one or more different individuals (e.g., healthy individuals), such as individuals of the same species. A “reference” can be determined empirically by testing a sufficiently large number of normal specimens.

[0253] As used herein, a tumor unless otherwise mentioned, is a cancerous tumor, and the terms cancer and tumor are used interchangeably throughout the document. While a tumor is a cancer of solid tissue, several of the compositions and methods described herein are in principle applicable to cancers of the blood, leukemia.Overview

[0254] After infusion of T cells (e.g., ex vivo activated T cells, or T-cell receptor engineered T cells (TCR-T cells)) into a patient with cancer, the cells can circulate until they encounter their cognate epitope, typically on a tumor cell. In the case of solid tumors, this can be challenging because the T cells can infiltrate the tumor and survive the harsh tumor microenvironment. Partly due to this challenge, infused T cell numbers and frequency may decline relatively rapidly after infusion. Additionally, the dose of infused TCR-T cells may be important in clinical response across several studies.

[0255] Methods to support the engraftment, expansion and persistence of infused T cells after infusion can include administering a vaccine that encodes the target antigen. In this case, however, the vaccine design can differ and may be a determinant of the success of this approach. The vaccine may encode for the full-length protein to be presented on the surface of cells. The vaccine can alternatively be designed around the minimal epitope target of the T cells. The vaccine strings designed to lead to optimal cleavage of the target epitopes can lead to more (e.g., 10-100 times more) of the desired epitope being presented on major histocompatibility complex (MHC) molecules encoded by HLA alleles than when the full-length PRAME protein is used. This method can enable the vaccine to induce robust display of the target epitope in a patient and subsequent stimulation of transferred T cells, whereas the dose attainable with the full-length PRAME protein may be insufficient in some cases.

[0256] The vaccine may encode targets epitopes presented by MHC molecules encoded by HLA-A*02:01, HLA-B*07:02, HLA-A*24:02, HLA-A*03:01, HLA-A*01:01, an HLA-C allele,and an HLA-B*08:01 allele. Provided herein are vaccine constructs to present at least the target epitope on each of these HLA alleles. There can be multiple considerations, including the order of the epitopes, the number of times each epitope is encoded, the codon optimization approach, and the mRNA format. A series of in vitro and in vivo assays can be used to select the vaccine design, e.g., by choosing the codon optimization approach and selecting the order of the epitopes. This information can be used to evaluate the vaccine designs in vivo. For example, the vaccine designs can be tested in a mouse model utilizing mice expressing human HLA. HLA-engineered tumor cells can also be utilized to evaluate the vaccine designs.FRAME Vaccines

[0257] The present disclosure provides PRAME vaccines comprising PRAME polypeptides or recombinant nucleic acids encoding PRAME polypeptides that, when expressed, can result in presentation of one or more epitopes of PRAME by one or more MHC molecules encoded by one or more HLA alleles.

[0258] Provided herein is a recombinant nucleic acid encoding a multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise a full length PRAME polypeptide. In some embodiments the multiepitopic polypeptide comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence. In some embodiments the multiepitopic polypeptide comprises a second PRAME amino acid sequence comprising a second PRAME epitope sequence. In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are different. In some embodiments, the first PRAME epitope sequence or second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope. In some embodiments, the first PRAME epitope sequence or second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the first PRAME epitope sequence or second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the first PRAME epitope sequence or second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*01:01. In some embodiments, the first PRAME epitope sequence or second PRAME epitope sequence comprises a common C-allele epitope.

[0259] In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide. In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length PRAME polypeptide. In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the recombinant nucleic acid encoding the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered a recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0260] In some embodiments, the first PRAME amino acid sequence is the first epitope sequence. In some embodiments, the second PRAME amino acid sequence is the second epitope sequence. In some embodiments, the first PRAME amino acid sequence is the first epitope sequence and the second PRAME amino acid sequence is the second epitope sequence. In some embodiments, the first PRAME amino acid sequence consists of the first epitope sequence. In some embodiments, the second PRAME amino acid sequence consists of the second epitope sequence. In some embodiments, the first PRAME amino acid sequence consists of the first epitope sequence and the second PRAME amino acid sequence consists of the second epitope sequence.

[0261] In some embodiments, the first PRAME epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length PRAME polypeptide. In some embodiments, the second PRAME epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length PRAME polypeptide.

[0262] In some embodiments, the first PRAME epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length PRAME polypeptide. In some embodiments, the second PRAME epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length PRAME polypeptide.

[0263] In some embodiments, the first PRAME amino acid sequence and the second PRAME amino acid sequence is separated by a linker. In some embodiments, the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the first PRAME epitope sequence from the full length PRAME polypeptide. In some embodiments, the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one, two, three, four, five or more residues flanking the N-terminus or C-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide.

[0264] In some embodiments the multiepitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more consecutive amino acids from the full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length PRAME polypeptide.

[0265] In some embodiments, the multiepitopic polypeptide further comprises a Secretory (Sec) sequence at the N terminus of the multiepitopic polypeptide. In some embodiments, the Sec sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence of SEQ ID NO: 1. In some embodiments, the Sec sequence comprises a sequence of SEQ ID NO: 1. In some embodiments, the Sec sequence is operably linked to the multiepitopic polypeptide via a linker. In some embodiments, the linker comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence of SEQ ID NO: 2. In some embodiments, the linker comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence of SEQ ID NO: 37. In someembodiments, the linker comprises a sequence of SEQ ID NO: 2. In some embodiments, the linker comprises a sequence of SEQ ID NO: 37.

[0266] In some embodiments, the multiepitopic polypeptide comprises an MHC class I trafficking signal (MITD) sequence at the C-terminus of the multiepitopic polypeptide. In some embodiments, the MITD sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence of SEQ ID NO: 34. In some embodiments, the MITD sequence comprises a sequence of SEQ ID NO: 34. In some embodiments, the multiepitopic polypeptide is operably linked to the MITD sequence via a linker. In some embodiments, the linker comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence of SEQ ID NO: 2. In some embodiments, the linker comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence of SEQ ID NO: 37. In some embodiments, the linker comprises a sequence of SEQ ID NO: 2. In some embodiments, the linker comprises a sequence of SEQ ID NO: 37.

[0267] In some embodiments, the multiepitopic polypeptide comprises at least 2 different PRAME epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 3 different PRAME epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 4 different PRAME epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 5 different PRAME epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 6 different PRAME epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 8 different PRAME epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 9 different PRAME epitope sequences. In some embodiments, the multiepitopic polypeptide comprises at least 10 or more different PRAME epitope sequences.

[0268] In some embodiments, the first PRAME epitope sequence and second PRAME epitope sequence are presentable by different HLA alleles. In some embodiments, the first PRAME epitope sequence and second PRAME epitope sequence are presented by different HLA alleles. In some embodiments, the first PRAME epitope sequence and second PRAME epitope sequence are predicted to bind to different HLA alleles. In some embodiments, the first PRAME epitopesequence and second PRAME epitope sequence are predicted to be presented by different HLA alleles.

[0269] In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KDless than 500 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KDless than 400 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KDless than 300 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele. In some embodiments, a first PRAME epitope sequence is predicted to bind to a first HLA allele. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KDless than 200 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KDless than 100 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KDless than 50 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KDless than 1 nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele. In some embodiments, a first PRAME epitope sequence is predicted to bind to a second HLA allele. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 200 nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 300 nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 500 nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 600nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 700 nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 800 nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 900nM. In some embodiments, a first PRAME epitope sequence binds to a second HLA allele with a KDof more than 1000 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KD of less than InM and binds to second HLA allele with a KDof more than 200 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KD of less than 50nM and binds to second HLA allele with a KDof more than 300 nM. In some embodiments, a first PRAME epitope sequence binds to a first HLA allele with a KD of less than lOOnM and binds to second HLA allele with a KDof more than 500 nM. In some embodiments, afirst PRAME epitope sequence binds to a first HLA allele with a KDof less than 200 nM and binds to second HLA allele with a KDof more than 600 nM.

[0270] The multispecific polypeptide can comprise one or more epitope sequences having an amino acid sequence from any one of the epitope sequences listed in Table 1. In some cases, the multispecific polypeptide can comprise one or more epitope sequences having an amino acid sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of the epitope sequences listed in Table 1.

[0271] In some embodiments, each of the sequences encoding the PRAME epitope sequences is flanked by one or more sequences encoding a cleavable linker sequence is selected from the group consisting of SEQ ID NOs: 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159, 161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% identity to a sequence of SEQ ID NO: 63. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 65. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 67. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, atleast 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 69. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 71. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 73. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 75. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 77. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 79. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 81. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 83. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 85. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 87. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 89. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 91. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 93. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 96. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, atleast 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 98. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 100. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 102. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 104. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 106. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 108. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 110. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequencecomprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 111. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 113. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 115. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 117. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 119. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 121. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 123. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequencesencoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 125. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 126. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 128. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 130. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 132. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 135. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 137. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises asequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 139. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 141. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 143. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 145. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 147. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 150. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 152. In some embodiments, the one or more sequences encoding acleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 152. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 157. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 159. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 161. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 163. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 168. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 170. In someembodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 173. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 175. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 178. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 180. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 182. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 183. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identityto a sequence of SEQ ID NO: 185. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 187. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 193. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 196. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 205. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 217. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 219. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, atleast 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 221. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 223. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 225. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 226. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 227. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 228. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 230. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, atleast 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 232. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 234. In some embodiments, the one or more sequences encoding a cleavable linker sequence comprises a sequence having at least the one or more sequences encoding a cleavable linker sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 236.

[0272] In some embodiments, the multiepitope polypeptide comprises a first PRAME epitope sequence, operably linked to a second PRAME epitope sequence, operably linked to a third PRAME epitope sequence.

[0273] In some embodiments, the recombinant nucleic acid comprises one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% identity to a sequence of SEQ ID NO: 64. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 66. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 68. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 70. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 72. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 74. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 76. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 80. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 82. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 84. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 86. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 88. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 90. In someembodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 92. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 97. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 99. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 101. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 103. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 105. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 107. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 109. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 112. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 114. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 116. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 118. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 120. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 122. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 124. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 127. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 129. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 131. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 133. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 134. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 136. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 138. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 140. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 142. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 144. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 146. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 148. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 149. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 151. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 154. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 155. In someembodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 156. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 158. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 160. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 162. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 164. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 166. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 167. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 169. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 171. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 172. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 174. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 176. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 177. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 179. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 181. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 184. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 186. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 188. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 189. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 191. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 192. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 194. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 195. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 197. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 198. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 199. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 200. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 201. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 202. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 203. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 204. In someembodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 206. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 207. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 218. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 220. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 222. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 224. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 229. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 231. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 233. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 235. In some embodiments, the recombinant nucleic acid comprises a sequence with at least 80%, at least85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 237.

[0274] The recombinant nucleic acid encoding the PRAME polypeptide can comprise one or more nucleic acid sequences each having a sequence selected from any one of the sequences listed in Table 2. In some cases, the recombinant nucleic acid can comprise one or more nucleic acid sequences each having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of the sequences listed in Table 2.

[0275] In some embodiments, the recombinant nucleic acid encoding the PRAME polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237. The recombinant nucleic acid encoding the PRAME polypeptide can comprise one or more copies of one or more sequences having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0276] In some embodiments, the recombinant nucleic acid encoding the PRAME polypeptide comprises two, three, four, five, six, seven, eight, nine, ten or more copies of one or more sequences having at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155,156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237. In some embodiments, the recombinant nucleic acid encoding the PRAME polypeptide comprises two, three, four, five, six, seven, eight, nine, ten or more copies of each of the sequences of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

[0277] In some embodiments, the recombinant nucleic acid comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*07:02, a sequence encoding a second epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*02:01, a sequence encoding a first epitope sequence presentable by HLA-A*01:01, a sequence encoding a second epitope sequence presentable by HLA-A*03:01, a sequence encoding a common C-allele epitope sequence, a sequence encoding a third epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*01:01, a sequence encoding a third epitope sequence presentable by HLA-A*01:01, and a sequence encoding a third epitope sequence presentable by HLA-B*08:01. In some embodiments, the recombinant nucleic acid comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding an epitope sequence presentable by HLA-A*01:01, a sequence encoding an epitope sequence presentable by HLA-B*07:02, a sequence encoding a common C-allele epitope sequence, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding an epitope sequence presentable by HLA-A*02:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, and a sequence encoding a second epitope sequence presentable by HLA-B*08:01.

[0278] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NO: 64, 70, 97, 103, 127, 133, 154, 176, 192, 197, 242, and 244. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 64. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 70. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 97. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 103. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 127. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 133. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 154. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 176. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 192. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 197. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 242. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 244.

[0279] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NO: 66, 74, 92, 99, 107, 124, 129, 136, 151, 155, 160, 174, 179, 191, 194, 198, 207, 229, 231, and 233. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 66. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 74. Insome embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 92. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 99. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 107. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 124. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 129. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 136. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 151. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 155. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 160. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 174. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 179. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 191. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 194. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 198. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 207. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 229. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 231. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 233.

[0280] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NO: 68, 82,86, 101, 114, 118, 131, 142, 146, 156, 166, 169, 177, 184, 186, 195, 201, 203, and 218. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 68. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 82. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 86. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 101. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 114. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 118. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 131. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 142. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 146. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 156. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 166. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 169. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 177. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 184. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 186. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 195. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 201. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 203. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 218.

[0281] In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 105, 134, 158, 105, 158, 222, and 240. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 105. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 134. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 158. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 105. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 158. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 222. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 240.

[0282] In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 76, 109, 138, 162, 181, 199, and 238. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 76. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 109. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 138. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 162. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 181. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 199. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 238.

[0283] In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 80, 88, 90, 112, 120, 122, 140, 148, 149, 164, 171, 172, 188, 189, 200, 204, 206, 220, 235, and 237. In some embodiments, the sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 80. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 88. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 90. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 112. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 120. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 122. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 140. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 148. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 149. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 164. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 171. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 172. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 188. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 189. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 200. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 204. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 206. In some embodiments, each sequence encoding anepitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 220. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 235. In some embodiments, each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 237.

[0284] In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 84, 116, 144, 167, 202, and 224. In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 84. In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 116. In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 144. In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 167. In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 202. In some embodiments, the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 224.

[0285] In some embodiments, the recombinant nucleic acid comprises, at the 5 ’end, a sequence encoding a Secretory (Sec) domain. In some embodiments, the sequence encoding a Sec domain comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 61. In some embodiments, the sequence encoding a Sec domain comprises a sequence of SEQ ID NO: 61. In some embodiments, the sequence encoding the Sec domain is operably linked to the recombinant nucleic via a sequence encoding a linker. In some embodiments, the sequence encoding a linker comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 62, 94, 208, and 215. In some embodiments, the sequence encoding a linker comprises a sequence of SEQ ID NO: 62. In some embodiments, the sequence encoding a linker comprises a sequence of SEQ ID NO: 94. In some embodiments, the sequenceencoding a linker comprises a sequence of SEQ ID NO: 208. In some embodiments, the sequence encoding a linker comprises a sequence of SEQ ID NO: 215.

[0286] In some embodiments, the recombinant nucleic acid comprises, at the 3 ’-end, a sequence encoding an MHC Class I Trafficking Signal (MITD) domain. In some embodiments, the sequence encoding an MITD domain comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 95 or SEQ ID NO: 216. In some embodiments, the sequence encoding an MITD domain comprises a sequence of SEQ ID NO: 95. In some embodiments, the sequence encoding an MITD domain comprises a sequence of SEQ ID NO: 216. In some embodiments, the sequence encoding the MITD domain is operably linked to the recombinant nucleic acid via a sequence encoding a linker. In some embodiments, the sequence encoding a linker comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 62, 94, 208, and 215. In some embodiments, the sequence encoding a linker comprises a sequence of SEQ ID NO: 62. In some embodiments, the sequence encoding a linker comprises a sequence of SEQ ID NO: 94. In some embodiments, the sequence encoding a linker comprises a sequence of SEQ ID NO: 208. In some embodiments, the sequence encoding a linker comprises a sequence of SEQ ID NO: 215.

[0287] In some embodiments, each of the sequences encoding an epitope sequence is flanked by one or more sequences encoding a cleavable linker. In some embodiments, the one or more sequences encoding the cleavable linker comprises a sequence with at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159, 161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 63. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 65. In some embodiments, the sequenceencoding the cleavable linker comprises a sequence of SEQ ID NO: 67. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 69. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 71. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 73. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 75. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 77. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 79. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 81. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 83. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 85. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 87. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 89. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 91. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 93. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 96. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 98. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 100. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 102. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 104. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 106. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 108. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 110. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 111. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 113. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 115. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 117. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 119. In some embodiments, the sequence encoding thecleavable linker comprises a sequence of SEQ ID NO: 121. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 123. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 125. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 126. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 128. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 130. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 132. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 135. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 137. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 139. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 141. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 143. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 145. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 147. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 150. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 152. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 152. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 157. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 159. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 161. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 163. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 168. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 170. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 173. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 175. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 178. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 180. In some embodiments, the sequence encoding the cleavable linkercomprises a sequence of SEQ ID NO: 182. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 183. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 185. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 187. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 193. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 196. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 205. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 217. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 219. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 221. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 223. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 225. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 226. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 227. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 228. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 230. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 232. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 234. In some embodiments, the sequence encoding the cleavable linker comprises a sequence of SEQ ID NO: 236.

[0288] In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of any one of SEQ ID NOs: 247-253, 255, 273, 274, and 293. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 247. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 248. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 249. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 250. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 251. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 252. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 253. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 255. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 273. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%sequence identity to a sequence of SEQ ID NO: 274. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 293. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 247. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 248. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 249. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 250. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 251. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 252. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 253. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 255. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 273. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 274. In some embodiments, the recombinant nucleic acid comprises a sequence of SEQ ID NO: 293. In some embodiments, the recombinant nucleic acid comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 254.

[0289] Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 245-253, 254-256, 273, 274, and 293. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 245. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 246. Also provided herein is a recombinant nucleic acid having at least 60%, at least65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 247. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 248. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 249. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 250. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 251. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 252. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 253. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 254. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 255. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 256. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 273. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 274. Also provided herein is a recombinant nucleic acid having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 293.

[0290] Also provided herein is a recombinant polypeptide encoded by any one of the recombinant nucleic acids described herein.

[0291] Also provided herein is a recombinant polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 35, 36, 38, 55, and 60. Also provided herein is a recombinant polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 35. Also provided herein is a recombinant polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 36. In some cases, the recombinant polypeptide comprises a variant of the sequence as set forth in SEQ ID NO: 36. For example, the recombinant polypeptide can comprise a variant sequence having a different C-terminal linker and / or N-terminal linker that is different from the C-terminal linker and / or N-terminal linker of SEQ ID NO: 36. The recombinant polypeptide can comprise the sequence as set forth in SEQ ID NO: 38. Also provided herein is a recombinant polypeptide having at least60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 38. Also provided herein is a recombinant polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 55. Also provided herein is a recombinant polypeptide having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 60.Immune Celis

[0292] The present disclosure provides immune cells (e.g., T cells) expressing a T cell receptor (TCR) or a chimeric antigen receptor. T cell receptors can also comprise endogenous T cell receptors that have been activated. Immune cells expressing a TCR can be activated and / or expanded using methods such as NEO-STIM. T cell receptors can comprise receptors encoded by recombinant nucleic acids that are specific for a PRAME polypeptide or fragment thereof.

[0293] Provided herein is a cell comprising any of the recombinant nucleic acids presented herein. In some embodiments, the cell is an immune cell. In some embodiments, the cell is a myeloid lineage cell. In some embodiments, the cell is a lymphocyte. In some embodiments, the cell is a B cell. In some embodiments, the cell is a T cell. In some cases, upon binding of the TCR to the peptide: MHC complex, the cell produces a pro inflammatory cytokine. In some cases, the proinflammatory cytokine is IFN-y. In some cases, the proinflammatory cytokine is TNF-a. In some cases, the proinflammatory cytokine is IL- 12. In some cases, the proinflammatory cytokine is IL-6. In some cases, the proinflammatory cytokine is IL- 17. In some embodiments, the proinflammatory cytokine is a chemokine. In some cases, upon binding of the TCR to the peptide: MHC complex, cell division is increased. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 2% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments,upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 5% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 10% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 15% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 25% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 50% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 100% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 150% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 200% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex. In some embodiments, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cell is increased by 500% or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.

[0294] Also provided herein is a recombinant nucleic acid encoding a TCR. In some embodiments, the TCR comprises a TCR beta chain construct. In some embodiments, the TCR comprises a TCR alpha chain construct. In some embodiments, the TCR binds to a peptide: MHC complex. In some embodiments, the peptide: MHC complex comprises (i) a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of SEQ ID NOs: 6, 14 and 32, and (ii) a human MHC encoded by the HLA-B*08:01 allele. In some embodiments, the peptide: MHC complex comprises (i) a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of SEQ ID NOs: 8, 22, and 26, and (ii) a human MHC encoded by the HLA-A*03:01 allele. In some embodiments, the peptide: MHC complex comprises (i) a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 28 or 30, and (ii) a human MHC encoded by the HLA-A*01:01 allele. In some embodiments, the peptide: MHC complex comprises (i) a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 24, and (ii) a human MHC encoded by an HLA-C allele.

[0295] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of SEQ ID NOs: 6, 14 and 32, and (ii) a human MHC encoded by the HLA-B*08:01 allele. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 14. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 32. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 6. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 14. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 32.

[0296] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of SEQ ID NOs: 8, 22 and 26, and (ii) a human MHC encoded by the HLA-A*03:01 allele. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 22. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, atleast 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 26. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 8. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 22. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 26.

[0297] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 28 or 30, and (ii) a human MHC encoded by the HLA-A*01:01 allele. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 28. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 30. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 28. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 30.

[0298] In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence having at least 5, at least 6, at least 7, at least 8, at least 9, at least 10 or more consecutive amino acids of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, atleast 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 24, and (ii) a human MHC encoded by the HLA-C allele. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 24. In some embodiments, the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 272. In some embodiments, the HLA-C allele is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02. In some embodiments, the HLA-C allele is HLA-C*04:01. In some embodiments, the HLA-C allele is HLA-C*06:02. In some embodiments, the HLA-C allele is HLA-C*07:01. In some embodiments, the HLA-C allele is HLA-C*03:04. In some embodiments, the HLA-C allele is HLA-C*08:02. In some embodiments, the HLA-C allele is HLA-C*05:01.Methods of Treatment

[0299] The methods of the disclosure can be used to treat any type of cancer known in the art. Non-limiting examples of cancers to be treated by the methods of the present disclosure can include melanoma (e.g., metastatic malignant melanoma), renal cancer (e.g., clear cell carcinoma), prostate cancer (e.g., hormone refractory prostate adenocarcinoma), pancreatic adenocarcinoma, breast cancer, colon cancer, lung cancer (e.g., non-small cell lung cancer), cutaneous melanoma, synovial sarcoma, myxoid and round cell liposarcoma, osteosarcoma, and neuroblastoma, esophageal cancer, squamous cell carcinoma of the head and neck, liver cancer, ovarian cancer, cervical cancer, thyroid cancer, glioblastoma, glioma, leukemia, lymphoma, and other neoplastic malignancies.

[0300] Additionally, the disease or condition provided herein includes refractory or recurrent malignancies whose growth may be inhibited using the methods of treatment of the present disclosure. In some embodiments, a cancer to be treated by the methods of treatment of the present disclosure is selected from the group consisting of carcinoma, squamous carcinoma, adenocarcinoma, sarcomata, endometrial cancer, breast cancer, ovarian cancer, cervical cancer, fallopian tube cancer, primary peritoneal cancer, colon cancer, colorectal cancer, squamous cell carcinoma of the anogenital region, melanoma and renal cell carcinoma.

[0301] Specific examples of cancers that can be prevented and / or treated in accordance with present disclosure include, but are not limited to, the following: renal cancer, kidney cancer, glioblastoma multiforme, metastatic breast cancer; breast carcinoma; breast sarcoma; neurofibroma; neurofibromatosis; pediatric tumors; neuroblastoma; malignant melanoma; carcinomas of the epidermis; leukemias such as but not limited to, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemias such as myeloblastic, promyelocytic, myelomonocytic, monocytic, erythroleukemia leukemias and myclodysplastic syndrome, chronic leukemias such as but not limited to, chronic myelocytic (granulocytic) leukemia, chronic lymphocytic leukemia, hairy cell leukemia; polycythemia vera; lymphomas such as but not limited to Hodgkin’s disease, non-Hodgkin’s disease; multiple myelomas such as but not limited to smoldering multiple myeloma, nonsecretory myeloma, osteosclerotic myeloma, plasma cell leukemia, solitary plasmacytoma and extramedullary plasmacytoma; Waldenstrom’s macroglobulinemia; monoclonal gammopathy of undetermined significance; benign monoclonal gammopathy; heavy chain disease; bone cancer and connective tissue sarcomas such as but not limited to bone sarcoma, myeloma bone disease, multiple myeloma, cholesteatoma-induced bone osteosarcoma, Paget’s disease of bone, osteosarcoma, chondrosarcoma, Ewing’s sarcoma, malignant giant cell tumor, fibrosarcoma of bone, chordoma, periosteal sarcoma, soft-tissue sarcomas, angiosarcoma (hemangiosarcoma), fibrosarcoma, Kaposi’s sarcoma, leiomyosarcoma, liposarcoma, lymphangio sarcoma, neurilemmoma, rhabdomyosarcoma, and synovial sarcoma; brain tumors such as but not limited to, glioma, astrocytoma, brain stem glioma, ependymoma, oligodendroglioma, nonglial tumor, acoustic neurinoma, craniopharyngioma, medulloblastoma, meningioma, pineocytoma, pineoblastoma, and primary brain lymphoma; breast cancer including but not limited to adenocarcinoma, lobular (small cell) carcinoma, intraductal carcinoma, medullary breast cancer, mucinous breast cancer, tubular breast cancer, papillary breast cancer, Paget’s disease (including juvenile Paget’s disease) and inflammatory breast cancer; adrenal cancer such as but not limited to pheochromocytom and adrenocortical carcinoma; thyroid cancer such as but not limited to papillary or follicular thyroid cancer, medullary thyroid cancer and anaplastic thyroid cancer; pancreatic cancer such as but not limited to, insulinoma, gastrinoma, glucagonoma, vipoma, somatostatin-secreting tumor, and carcinoid or islet cell tumor; pituitary cancers such as but limited to Cushing’s disease, prolactin-secreting tumor, acromegaly, and diabetes insipius; eye cancers such as but not limited to ocular melanoma suchas iris melanoma, choroidal melanoma, and cilliary body melanoma, and retinoblastoma; vaginal cancers such as squamous cell carcinoma, adenocarcinoma, and melanoma; vulvar cancer such as squamous cell carcinoma, melanoma, adenocarcinoma, basal cell carcinoma, sarcoma, and Paget’s disease; cervical cancers such as but not limited to, squamous cell carcinoma, and adenocarcinoma; uterine cancers such as but not limited to endometrial carcinoma and uterine sarcoma; ovarian cancers such as but not limited to, ovarian epithelial carcinoma, borderline tumor, germ cell tumor, and stromal tumor; cervical carcinoma; esophageal cancers such as but not limited to, squamous cancer, adenocarcinoma, adenoid cystic carcinoma, mucoepidermoid carcinoma, adenosquamous carcinoma, sarcoma, melanoma, plasmacytoma, verrucous carcinoma, and oat cell (small cell) carcinoma; stomach cancers such as but not limited to, adenocarcinoma, fungating (polypoid), ulcerating, superficial spreading, diffusely spreading, malignant lymphoma, liposarcoma, fibrosarcoma, and carcinosarcoma; colon cancers; colorectal cancer, colon carcinoma; rectal cancers; liver cancers such as but not limited to hepatocellular carcinoma and hepatoblastoma, gallbladder cancers such as adenocarcinoma; cholangiocarcinomas such as but not limited to pappillary, nodular, and diffuse; lung cancers such as non-small cell lung cancer, non-small cell lung cancer, squamous cell carcinoma (epidermoid carcinoma), adenocarcinoma, large-cell carcinoma and small-cell lung cancer; lung carcinoma; testicular cancers such as but not limited to germinal tumor, seminoma, anaplastic, classic (typical), spermatocytic, nonseminoma, embryonal carcinoma, teratoma carcinoma, choriocarcinoma (yolk-sac tumor), prostate cancers such as but not limited to, androgenindependent prostate cancer, androgen-dependent prostate cancer, adenocarcinoma, leiomyosarcoma, and rhabdomyosarcoma; penal cancers; oral cancers such as but not limited to squamous cell carcinoma; basal cancers; salivary gland cancers such as but not limited to adenocarcinoma, mucoepidermoid carcinoma, and adenoidcystic carcinoma; pharynx cancers such as but not limited to squamous cell cancer, and verrucous; skin cancers such as but not limited to, basal cell carcinoma, squamous cell carcinoma and melanoma, superficial spreading melanoma, nodular melanoma, lentigo malignant melanoma, acrallentiginous melanoma; kidney cancers such as but not limited to renal cell cancer, adenocarcinoma, hypernephroma, fibrosarcoma, transitional cell cancer (renal pelvis and / or uterus); renal carcinoma; Wilms’ tumor; bladder cancers such as but not limited to transitional cell carcinoma, squamous cell cancer, adenocarcinoma, carcinosarcoma. In addition, cancers include myxosarcoma, osteogenicsarcoma, endotheliosarcoma, lymphangioendotheliosarcoma, mesothelioma, synovioma, hemangioblastoma, epithelial carcinoma, cystadenocarcinoma, bronchogenic carcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma and papillary adenocarcinomas. Cancers include, but are not limited to, B cell cancer, e.g., multiple myeloma, Waldenstrom’s macroglobulinemia, the heavy chain diseases, such as, for example, alpha chain disease, gamma chain disease, and mu chain disease, benign monoclonal gammopathy, and immunocytic amyloidosis, melanomas, breast cancer, lung cancer, bronchus cancer, colorectal cancer, prostate cancer (e.g., metastatic, hormone refractory prostate cancer), pancreatic cancer, stomach cancer, ovarian cancer, urinary bladder cancer, brain or central nervous system cancer, peripheral nervous system cancer, esophageal cancer, cervical cancer, uterine or endometrial cancer, cancer of the oral cavity or pharynx, liver cancer, kidney cancer, testicular cancer, biliary tract cancer, small bowel or appendix cancer, salivary gland cancer, thyroid gland cancer, adrenal gland cancer, osteosarcoma, chondrosarcoma, cancer of hematological tissues, and the like. Other non-limiting examples of types of cancers applicable to the methods encompassed by the present disclosure include human sarcomas and carcinomas, e.g., fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing’s tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, colorectal cancer, pancreatic cancer, breast cancer, ovarian cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, liver cancer, choriocarcinoma, seminoma, embryonal carcinoma, Wilms’ tumor, cervical cancer, bone cancer, brain tumor, testicular cancer, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma, retinoblastoma; leukemias, e.g., acute lymphocytic leukemia and acute myelocytic leukemia (myeloblastic, promyelocytic, myelomonocytic, monocytic and erythroleukemia); chronic leukemia (chronic myelocytic (granulocytic) leukemia and chronic lymphocytic leukemia); and polycythemia vera, lymphoma (Hodgkin’s disease and nonHodgkin’s disease), multiple myeloma, Waldenstrom’s macroglobulinemia, and heavy chaindisease. In some embodiments, the cancer whose phenotype is determined by the method of the present disclosure is an epithelial cancer such as, but not limited to, bladder cancer, breast cancer, cervical cancer, colon cancer, gynecologic cancers, renal cancer, laryngeal cancer, lung cancer, oral cancer, head and neck cancer, ovarian cancer, pancreatic cancer, prostate cancer, or skin cancer. In other embodiments, the cancer is breast cancer, prostate cancer, lung cancer, or colon cancer. In still other embodiments, the epithelial cancer is non-small-cell lung cancer, nonpapillary renal cell carcinoma, cervical carcinoma, ovarian carcinoma (e.g., serous ovarian carcinoma), or breast carcinoma. The epithelial cancers may be characterized in various other ways including, but not limited to, serous, endometrioid, mucinous, clear cell, brenner, or undifferentiated. In some embodiments, the present disclosure is used in the treatment, diagnosis, and / or prognosis of lymphoma or its subtypes, including, but not limited to, mantle cell lymphoma. Lymphoproliferative disorders are also considered to be proliferative diseases.

[0302] In some cases, the disease or condition is cancer. Cancer refers to diseases in which abnormal cells divide out of control and are able to invade other tissues. Cancer cells can spread to other parts of the body through the blood and lymph systems. Cancer can be characterized as a group of diseases involving abnormal cell growth that may begin in any tissue with the potential to invade or spread to other parts of the body. Some cancers can be characterized by their type, e.g., solid cancers, liquid cancers, or based on cellular origin such as hematopoietic cancers, osteosarcoma or lymphoma. Some cancers are known by the tissue of their origin or prevalence, e.g., endometrial cancers are characterized as cancers of the endometrial tissue. Some cancers are known by the organ or site of their origin or prevalence, e.g. lung cancer, head and neck cancer. Some cancers may be known by the overproductions of certain proteins, enzymes or biomarkers compared to their counterpart cells or tissues that are not cancerous. For example, certain proteins of viral origin may be associated with certain cancers, such as HPV-16 cancers, where certain proteins, for example HPV-16 E6 and E7 are overexpressed in cancer cells of this type. For example, certain antigens, such as KRAS may be highly expressed in certain cancer types, compared to non-cancer cells of the same type, and may be designated as KRAS overexpressing cancers. Typically, the overexpression of the antigen or the specific protein may be associated with or related to one or more mutations, and the cancer type may be associated with the mutation. For example, mutation at the wild type G residue corresponding to position 12 in KRAS amino acid sequence may be mutated to V, D, C or other amino acids in KRAS-specificcancer cells. Certain specific antigens may be specifically expressed in cancer cells of certain cancer types, and not in other cancer types. Various cancers are contemplated herein that may not be restricted to a specific cell type, tissue type or organ, or even a certain stage of cancer. The TCRs of the present disclosure can be directed to cancer cells that express a cancer antigen, that may be patient specific, which can be found during sequencing of a subject’s genome from biological sample obtained from a cancer cell, cancer site or cancer tissue and compared to a corresponding non-cancer sample from the same subject; wherein the patient-specific antigen may be expressed in the cancer cell, and not on the non-cancer cell of the subject. In some cases, cancer antigens may be cancer specific, where the antigen is reportedly present in the type of cancer observed in multiple patients in the human population, who have been diagnosed of the specific cancer. In some cases, certain types are cancers are associated with an antigen, a protein (e.g., a viral protein) a gene mutation. All forms of cancer are contemplated herein.

[0303] In some embodiments, the cancer is a solid cancer. In some cases, the cancer is a liquid / blood cancer. The cancer can express or be diagnosed as expressing a tumor antigen. The tumor antigen can be a tumor-associated antigen or a tumor-specific antigen. In some cases, the cancer expresses a tumor-associated antigen (TAA). In some cases, the cancer expresses a tumorspecific antigen (TSA).

[0304] In some embodiments, the cancer is a cancer expressing or diagnosed as expressing a TAA. In some embodiments, the cancer is a cancer expressing or diagnosed as expressing a TSA.

[0305] The current classification of TAA can include the following group:a) Cancer testis (CT) antigen: Since testis cells do not express HLA class I and class II molecules, these antigens may not be recognized by T cells in normal tissues and may therefore be immunologically considered tumor specific. Non-limiting examples of CT antigens include members of the MAGE family and NY-ESO-1;b) Differentiation antigen: both tumor and normal tissue (from which the tumor originates) may contain TAAs. Differentiation antigens may be found, for example, in melanoma and normal melanocytes. Many of these melanocyte lineage-associated proteins may be involved in melanin biosynthesis and therefore these proteins may not tumor-specific, but may still widely be used for immunotherapy of cancer. Examples include, but are not limited to, tyrosinase for melanoma and PSA for Melan-A / MART-1 or prostate cancer;c) Overexpressed TAA: gene-encoded widely expressed TAAs may be detected in histologically diverse tumors and in many normal tissues, with generally low expression levels. It is possible that many epitopes processed and potentially presented by normal tissues may be below the threshold level of T cell recognition, whereas their overexpression in tumor cells can trigger anticancer responses by breaking previously established tolerance. Non-limiting examples of such TAAs include Her-2 / neu, survivin, telomerase or WT1;d) tumor specific antigen can include unique TAAs resulted from mutations in normal genes (e.g., beta-catenin, CDK4). Some of these molecular changes can be associated with neoplastic transformation and / or progression. Tumor-specific antigens can generally induce strong immune responses without risking from the autoimmune response to normal tissue strips. On the other hand, these TAAs may only be associated with the exact tumor on which they are confirmed, and may not commonly shared among many individual tumors. In the case of tumor specific (related) isoform proteins, peptide tumor specificity (or relatedness) may also occur if the peptide is derived from tumor (related) exons;e) TAA resulting from aberrant post-translational modification: such TAAs may result from proteins in the tumor that are neither specific nor overexpressed, but which still have tumor relevance (this relevance is due to posttranslational processing that is primarily active on tumors). Such TAAs may result from an altered glycosylation pattern, resulting in a tumor producing a novel epitope for MUC1 or in an event such as protein splicing during degradation, which may or may not be tumor specific; andf) Tumor virus protein: these TTAs are viral proteins that may play a key role in the oncogenic process and, because they are foreign proteins (non-human proteins), may be able to trigger T cell responses. Non-limiting examples of such proteins include human papilloma type 16 viral proteins, E6 and E7, which are expressed in cervical cancer.

[0306] Examples of tumor antigens include, but not limited to new antigens expressed during tumorigenesis, products of oncogenes and tumor suppressor genes, overexpressed or abnormally expressed intracellular proteins (e.g., HER2, MUC1, PSA, MUC1), carcinoembryonic antigen (CEA), tumor viruses (e.g., EBC, HPV, HBV, HCB, HTLV), cancer testis antigens (CTA) (e.g., MAGE family, NY-ESO), oncofetal antigens, altered surface glycolipids and glycoproteins, cell type-specific differentiation antigens (e.g., MART-1), or a derivative thereof. The tumor antigens can be selected from the group consisting of NY-ESO-1, Her2 / neu, SSX-2, MAGE-C2,MAGE-A1, M-2433-233, MAGE-A10254-262, KK-LC-1, p53, PRAME, Alpha fetoprotein, HPV6-E6, HPV16-E7, EBV-LMP1, RAS: G12D, RAS: G12C, RAS: G12A, RAS: G12S, RAS: G12R, RAS: G12R, RAS: G12R, RAS: G122 V, RAS: Q61H, RAS: Q61L, RAS: Q61R, RAS: G13D, TP53: V157G, TP53: V157F, TP53: R248Q, TP53: R248W, TP53: G245S, TP53:Y163C, TP53: G249S, TP53: Y240C, TP53: R175H, TP53: K132N, CDC73: Q254E, TPP2A6: N438Y, CTNN1: T41A, CTNNB1: S45P, CTNNB1: S37Y, CTNNB1: S33C, EGFR: L858R, EGFR: T790M, PIK3CA: E542K, PIK3CA: H1047R, GNAS: R201H, CDK4: R24, R24C H3. 3: K28M, BRAF: V600E, CHD4 K73Rfs, NRAS Q61R, IDH1: R132H, TVP23C: C51Y, and any combination thereof. The RAS can be KRAS, HRAS, or NRAS.

[0307] Other non-limiting examples of tumor-associated antigen or tumor-specific antigen includes antigens from Human Papilloma Virus, Epstein-Barr Virus, Merkel cell polyomavirus, Human Immunodeficiency Virus, Human T-cell Leukemia Virus, Human Herpes Virus 8, Hepatitis B virus, Hepatitis C virus, HCV, HBC, Cytomegalovirus, or from the group of singlepoint mutated antigens derived from the group consisting of the antigens of ctnnbl gene, casp8 gene, HER2 gene, p53 gene, KRAS gene, NRAS gene, or particular tumor antigens issued or derived from the group consisting of RAS oncogene, BCR-ABL tumor antigens, ETV6-AML1 tumor antigens, melanoma-antigen encoding genes (MAGE), BAGE antigens, GAGE antigens, ssx antigens, ny-eso-1 antigens, cyclin-Al tumor antigens, MART-1 antigen, gplOO antigen, CD 19 antigen, prostate specific antigen, prostatic acidic phosphatase antigen, carcinoembryonic antigen, alphafetoprotein antigen, carcinoma antigen 125, mucin 16 antigen, mucin 1 antigen, human telomerase reverse transcriptase antigen, EGFR antigen, MOK antigen, RAGE-1 antigen, PRAME antigen, wild-type p53 antigen, oncogene ERBB2 antigen, sialyl-Tn tumor antigen, Wilms tumor 1 antigen, mesothelin antigen, carbohydrate antigens, B-catenin antigen, MUM-1 antigen, CDK4 antigen ERBB2IP antigen, and Melan-A melanoma tumor-associated antigen.

[0308] In some cases, the cancer cells express the tumor antigens, including and not limited to, NY-ESO-1, Her2 / neu, SSX-2, MAGE-C2, MAGE-A1, M-2433-233, MAGE-A10254-262, KK-LC-1, p53, PRAME, Alpha fetoprotein, HPV6-E6, HPV16-E7, EBV-LMP1, RAS: G12D, RAS: G12C, RAS: G12A, RAS: G12S, RAS: G12R, RAS: G12R, RAS: G12R, RAS: G122 V, RAS: Q61H, RAS: Q61L, RAS: Q61R, RAS: G13D, TP53: V157G, TP53: V157F, TP53: R248Q, TP53: R248W, TP53: G245S, TP53: Y163C, TP53: G249S, TP53: Y240C, TP53: R175H, TP53: K132N, CDC73: Q254E, TPP2A6: N438Y, CTNN1: T41A, CTNNB1: S45P, CTNNB1: S37Y,CTNNB1: S33C, EGFR: L858R, EGFR: T790M, PIK3CA: E542K, PIK3CA: H1047R, GNAS: R201H, CDK4: R24, R24C H3. 3: K28M, BRAF: V600E, CHD4 K73Rfs, NRAS Q61R, IDH1:R132H, or TVP23C: C51Y. The RAS can be KRAS, HRAS, or NRAS.

[0309] Provided herein is a method of treating a subject with a disease or condition. In some embodiments, the method comprises administering to the subject a therapy comprising a multiepitopic polypeptide. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the multi epitopic polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the multiepitopic polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise a full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence. In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are different. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope. In some embodiments, at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA- A* 01: 01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises a common C-allele epitope.

[0310] In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the first PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the epitope sequence presentable by HLA-B*08:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of any one of SEQ ID NOs: 6, 14 and 32. In some embodiments, the epitope sequence presentable by HLA-B*08:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6. In some embodiments, the epitope sequence presentable by HLA-B*08:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 14. In some embodiments, the epitope sequence presentable by HLA-B*08:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 32. In some embodiments, the epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 6.. In some embodiments, the epitope sequence presentable by HLA-B*08:01 comprises a sequence of SEQ ID NO: 14. In some embodiments, the epitope sequence presentable by HLA-B* 08:01 comprises a sequence of SEQ ID NO: 32.

[0311] In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the first PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, atleast 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of any one of SEQ ID NOs: 8, 22, and 26. In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 8. In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 22. In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 26. In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 8. In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 22. In some embodiments, the epitope sequence presentable by HLA-A*03:01 comprises a sequence of SEQ ID NO: 26.

[0312] In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*01:01. In some embodiments, the first PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*01:01. In some embodiments, the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*01:01. In some embodiments, the epitope sequence presentable by HLA-A*01:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 28 or 30. In some embodiments, the epitope sequence presentable by HLA-A*01:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 28. In some embodiments, the epitope sequence presentable by HLA-A*01:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%,at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 30. In some embodiments, the epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 28. the epitope sequence presentable by HLA-A*01:01 comprises a sequence of SEQ ID NO: 30.

[0313] In some embodiments, the common C-allele epitope is presentable by an HLA-C. In some embodiments, the HLA-C is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02. In some embodiments, the HLA-C is HLA-C*04:01. In some embodiments, the HLA-C is HLA-C*06:02. In some embodiments, the HLA-C is HLA-C*07:01. In some embodiments, the HLA-C is HLA-C* 03: 04. In some embodiments, the HLA-C is HLA-C*08:02. In some embodiments, the common C-allele epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 24. In some embodiments, the common C-allele epitope sequence comprises a sequence of SEQ ID NO: 24.

[0314] In some embodiments, the multiepitopic polypeptide further comprises a linker for analytics. In some embodiments, the linker for analytics comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 18. In some embodiments, the linker for analytics comprises a sequence of SEQ ID NO: 18.

[0315] In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide. In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitopesequence as the peptide: MHC complex by the APCs of a subject administered the full-length PRAME polypeptide. In some embodiments, presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the recombinant nucleic acid encoding the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered a recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0316] In some embodiments, the method further comprises administering to the subject a T-cell receptor (TCR). In some embodiments, the method further comprises administering to the subject a recombinant nucleic acid encoding the TCR.

[0317] In some embodiments, the first PRAME amino acid sequence is the first epitope sequence and / or the second PRAME amino acid sequence is the second epitope sequence. In some embodiments, the first PRAME amino acid sequence is the first epitope sequence. In some embodiments, the second PRAME amino acid sequence is the second epitope sequence. In some embodiments, the first PRAME amino acid sequence is the first epitope sequence and the second PRAME amino acid sequence is the second epitope sequence. In some embodiments, the first PRAME amino acid sequence consists of the first epitope sequence and / or the second PRAME amino acid sequence consists of the second epitope sequence. In some embodiments, the first PRAME amino acid sequence consists of the first epitope sequence. In some embodiments, the second PRAME amino acid sequence consists of the second epitope sequence. In some embodiments, the first PRAME amino acid sequence consists of the first epitope sequence and the second PRAME amino acid sequence consists of the second epitope sequence.

[0318] In some embodiments, the first PRAME epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length PRAME polypeptide. In some embodiments, the second PRAME epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length PRAME polypeptide.

[0319] In some embodiments, the first PRAME epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length PRAME polypeptide. In some embodiments, the second PRAME epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length PRAME polypeptide.

[0320] In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence is separated by a linker. In some embodiments, the first PRAME amino acid sequence and the second PRAME amino acid sequence is separated by a linker.

[0321] In some embodiments, the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one, two, three, four, five, six, seven, eight, nine, ten or more residues flanking the N-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide. In some embodiments, the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one, two, three, four, five, six, seven, eight, nine, ten or more residues flanking the C-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide.

[0322] In some embodiments, the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one, two, three, four, five, six, seven, eight, nine, ten or more residues flanking the N-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide. In some embodiments, the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one, two, three, four, five, six, seven, eight, nine, ten or more residues flanking the C-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide.

[0323] In some embodiments, the multiepitopic polypeptide does not comprise more than 15 or more consecutive amino acids from the full length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 16 or more consecutive amino acids from the full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 18 or more consecutive amino acids from the full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 20 or more consecutive amino acids from the full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 22 or more consecutive amino acids from the full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 24 or more consecutive amino acids from the full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 28 or more consecutive amino acids from the full-length PRAMEpolypeptide. In some embodiments, the multiepitopic polypeptide does not comprise more than 30 or more consecutive amino acids from the full-length PRAME polypeptide.

[0324] In some embodiments, the TCR recognizes and binds to a peptide: MHC complex. In some embodiments, the peptide: MHC complex comprises the first PRAME epitope sequence and a human MHC encoded by an HLA allele. In some embodiments, the peptide: MHC complex comprises the second PRAME epitope sequence and a human MHC encoded by an HLA allele.

[0325] Also provided herein is a method of treating a subject with a disease or condition. In some embodiments, the method comprises administering to the subject a therapy comprising a multiepitopic polypeptide. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the multi epitopic polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the multiepitopic polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise a full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence. In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are different. In some embodiments, at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA- A* 01:01, and a common C-allele epitope. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA- A* 01: 01. In someembodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises a common C-allele epitope. In some embodiments, the subject has been previously administered a T-cell receptor (TCR). In some embodiments, the subject has been previously administered a recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide: MHC complex. In some embodiments, the peptide: MHC complex comprises the first PRAME epitope sequence and a human MHC encoded by an HLA allele. In some embodiments, the peptide: MHC complex comprises the second PRAME epitope sequence and a human MHC encoded by an HLA allele.

[0326] Also provided herein is a method of treating a subject with a disease or condition. In some embodiments, the method comprises administering to the subject a T-cell receptor (TCR). In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide: MHC complex. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence and a human MHC encoded by an HLA allele. In some embodiments, the subject has been previously administered a PRAME polypeptide. In some embodiments, the subject has been previously administered a recombinant nucleic acid encoding the PRAME polypeptide. In some embodiments, the subject has been previously administered a cell comprising the recombinant nucleic acid encoding the PRAME polypeptide. In some embodiments, the PRAME polypeptide comprises a multiepitopic polypeptide that does not comprise a full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence. In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are different. In some embodiments, at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA- A* 01:01, and a common C-allele epitope. In some embodiments,the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA- A* 01: 01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises a common C-allele epitope.

[0327] Provided herein is a method of treating a subject with a disease or condition. In some embodiments, the method comprises administering to the subject a therapy comprising a multiepitopic polypeptide. In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the multi epitopic polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the multiepitopic polypeptide. In some embodiments, the method comprises administering to the subject a cell comprising the recombinant nucleic acid encoding the multiepitopic polypeptide. In some embodiments, the multiepitopic polypeptide does not comprise a full-length PRAME polypeptide. In some embodiments, the multiepitopic polypeptide comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence. In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are different. In some embodiments, at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA- A* 01:01, and a common C-allele epitope. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, the first PRAME epitope sequence or the second PRAMEepitope sequence comprises an epitope sequence presentable by HLA- A* 01: 01. In some embodiments, the first PRAME epitope sequence or the second PRAME epitope sequence comprises a common C-allele epitope. In some embodiments, the method comprises administering to the subject a T-cell receptor (TCR). In some embodiments, the method comprises administering to the subject a recombinant nucleic acid encoding the TCR. In some embodiments, the TCR recognizes and binds to a peptide: MHC complex. In some embodiments, the peptide: MHC complex comprises a PRAME epitope sequence and a human MHC encoded by an HLA allele.

[0328] In some embodiments, administering the PRAME polypeptide, the recombinant nucleic acid encoding the PRAME polypeptide, or the cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is performed concurrently with administering the TCR or the recombinant nucleic acid encoding the TCR. In some embodiments, administering the PRAME polypeptide, the recombinant nucleic acid encoding the PRAME polypeptide, or the cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is performed prior to administering the TCR or the recombinant nucleic acid encoding the TCR. In some embodiments, administering the PRAME polypeptide, the recombinant nucleic acid encoding the PRAME polypeptide, or the cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is performed subsequent to administering the TCR or the recombinant nucleic acid encoding the TCR.

[0329] The PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR. The PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, ormore after the subject has been administered an immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR.

[0330] The TCR or the recombinant nucleic acid encoding the TCR can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide. The immune cell comprising the TCR or the recombinant nucleic acid encoding the TCR can be administered at least 1 hour, 2 hours, 3 hours, 5 hours, 10 hours, 12 hours, 15 hours, 20 hours, 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 1 year, 2 years, 3 years, 4 years, 5 years, or more after the subject has been administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide.

[0331] In some embodiments, the TCR is expressed by an immune cell. In some embodiments, the recombinant nucleic acid encoding the TCR is expressed by an immune cell. In some embodiments, the TCR is a soluble TCR. In some embodiments, the method comprises administering two or more different TCRs. In some embodiments, the method comprises administering two or more recombinant nucleic acids encoding the two or more different TCRs. In some embodiments, the two or more TCRs comprise a first TCR and a second TCR. In some embodiments, the two or more different TCRs are expressed on the surface of two different immune cells. In some embodiments, the first TCR and the second TCR bind to different peptide: MHC complexes, each peptide: MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele. In some embodiments, the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture. In some embodiments, the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are administered separately. In some embodiments, the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are co-administered in a same mixture.

[0332] In some embodiments, each of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting ofan epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A* 03: 01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope. In some embodiments, each of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01. In some embodiments, each of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*03:01. In some embodiments, each of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-A*01:01. In some embodiments, each of the first PRAME epitope sequence and the second PRAME epitope sequence comprises a common C-allele epitope.

[0333] In some embodiments, the first PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02. In some embodiments, the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, and the first PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02.

[0334] In some embodiments, the PRAME polypeptide comprises one or more additional PRAME epitope sequences. In some embodiments, the PRAME polypeptide comprises one, two, three, four, five, six, seven, eight, nine, ten or more additional PRAME epitope sequences. In some embodiments, the one or more additional PRAME epitope sequences comprise one or more epitope sequences selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02, and any combination thereof. In some embodiments, the one or more additional PRAME epitope sequences comprise an epitope sequence presentable by an HLA-A*24:02. In some embodiments, the one or more additional PRAME epitope sequencescomprise an epitope sequence presentable by an HLA-A*02:01. In some embodiments, the one or more additional PRAME epitope sequences comprise an epitope sequence presentable by an HLA-B*07:02. In some embodiments, the one or more additional PRAME epitope sequences comprise an epitope sequence presentable by an HLA-A*24:02 and an epitope sequence presentable by an HLA-A*02:01. In some embodiments, the one or more additional PRAME epitope sequences comprise an epitope sequence presentable by an HLA-A*24:02 and an epitope sequence presentable by an HLA-B*07:02. In some embodiments, the one or more additional PRAME epitope sequences comprise an epitope sequence presentable by an HLA-A*02:01 and an epitope sequence presentable by an HLA-B*07:02. In some embodiments, the one or more additional PRAME epitope sequences comprise an epitope sequence presentable by an HLA-A*24:02, an epitope sequence presentable by an HLA-A*02:01, and an epitope sequence presentable by an HLA-B*07:02.

[0335] In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of any one of SEQ ID NOs: 4, 10, 58, and 59. In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 4. In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 10. In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 4. In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 10. In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 58. In some embodiments, the epitope sequence presentable by HLA-A*24:02 comprises a sequence of SEQ ID NO: 59.

[0336] In some embodiments, the epitope sequence presentable by HLA-A*02:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%,at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 16 or SEQ ID NO: 56. In some embodiments, the epitope sequence presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

[0337] In some embodiments, the epitope sequence presentable by HLA-B*07:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to a sequence of SEQ ID NO: 12 or SEQ ID NO: 57. In some embodiments, the epitope sequence presentable by HLA-B*07:01 comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

[0338] In some embodiments, the first TCR binds to a peptide comprising an epitope sequence of SEQ ID NO: 16 and an MHC encoded by an HLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele.

[0339] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 16 and an MHC encoded by an HLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele.

[0340] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele.

[0341] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26 and an MHC encoded by an HLA-A*03:01 allele.

[0342] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising anepitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele.

[0343] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

[0344] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele.

[0345] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

[0346] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

[0347] In some embodiments, the epitope sequence presentable by HLA-A*02:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 16 or SEQ ID NO: 56.

[0348] In some embodiments, the epitope sequence presentable by HLA-B*07:01 comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 12 or SEQ ID NO: 57.

[0349] In some embodiments, the first TCR binds to a peptide comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 16 and an MHC encoded by anHLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele.

[0350] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 16 and an MHC encoded by an HLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele.

[0351] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele.

[0352] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100%sequence identity to SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26 and an MHC encoded by an HLA-A*03:01 allele.

[0353] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele.

[0354] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

[0355] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele.

[0356] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

[0357] In some embodiments, the first TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

[0358] In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 16 or SEQ ID NO: 56. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56. In some embodiments, the HLA allele is an HLA-A*02:01 allele.

[0359] In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 12 or SEQ ID NO: 57. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57. In some embodiments, the HLA allele is an HLA-B*07:02 allele.

[0360] In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 4. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 4. In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 10. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 10. In some embodiments, the HLA allele is an HLA-A*24:02 allele.

[0361] In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 6. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 6. In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 14. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 14. In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 32. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 32. In some embodiments, the HLA allele is an HLA-B*08:01 allele.

[0362] In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 8. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 8. In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 22. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 22. In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 26. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 26. In some embodiments, the HLA allele is an HLA-A*03:01 allele.

[0363] In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 20. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 20. In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 28. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 28. In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 30. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 30. In some embodiments, the HLA allele is an HLA-A*01:01 allele.

[0364] In some embodiments, the PRAME epitope sequence comprises a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NO: 24. In some embodiments, the PRAME epitope sequence comprises a sequence of SEQ ID NO: 24. In some embodiments, the HLA allele is an HLA-C allele. In some embodiments, the HLA-C allele is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02.In some embodiments, the HLA-C allele is HLA-C*04:01. In some embodiments, the HLA-C allele is HLA-C*06:02. In some embodiments, the HLA-C allele is HLA-C*07:01. In some embodiments, the HLA-C allele is HLA-C*06:02. In some embodiments, the HLA-C allele is HLA-C*03:04. In some embodiments, the HLA-C allele is HLA-C*08:02.

[0365] In some embodiments, the first and second PRAME epitope sequences are separated by one or more linker sequences. In some embodiments, the one or more linker sequences are selected from the group consisting of a sequence having at least 60%, at least 65%, at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or 100% sequence identity to SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 21, 23, 25, 27, 29, 31, 33, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, and any combination thereof. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 3. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 5. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 7. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 9. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 11. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 13. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 15. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 17. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 21. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 23. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 25. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 27. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 29. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 31. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 33. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 39. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 40. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 41. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 42. In some embodiments, the one or more linkersequences comprise a sequence of SEQ ID NO: 43. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 45. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 46. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 47. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 48. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 49. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 50. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 51. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 52. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 53. In some embodiments, the one or more linker sequences comprise a sequence of SEQ ID NO: 54.

[0366] In some cases, antigen presenting cells (APCs) of subject administered the PRAME polypeptide present a PRAME epitope sequence as a peptide: MHC complex. In some cases, antigen presenting cells of subject administered the nucleic acid encoding the PRAME polypeptide comprising the multiepitopic polypeptide present a PRAME epitope sequence as a peptide: MHC complex. In some cases, the APCs present more of a PRAME epitope as a peptide: MHC complex compared to the APCs of a subject administered a full length PRAME polypeptide or recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0367] In some embodiments, T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

[0368] In some embodiments, the first PRAME amino acid sequence is the first PRAME epitope sequence. In some embodiments the second PRAME amino acid sequence is the second PRAME epitope sequence. In some embodiments, the first PRAME amino acid sequence is the first PRAME epitope sequence, and the second PRAME amino acid sequence is the second PRAME epitope sequence. In some embodiments, the first PRAME amino acid sequence consists of the first PRAME epitope sequence. In some embodiments, the second PRAME amino acid sequence consists of the second PRAME epitope sequence. In some embodiments, the first PRAME aminoacid sequence consists of the first PRAME epitope sequence, and the second PRAME amino acid sequence consists of the second PRAME epitope sequence.

[0369] In some embodiments, the first PRAME epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length PRAME polypeptide. In some embodiments, the second PRAME epitope sequence consists of from 5 to 18, from 6 to 17, from 5 to 16, from 7 to 12, or from 8 to 10 consecutive amino acids from the full length PRAME polypeptide.

[0370] In some embodiments, the first PRAME epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length PRAME polypeptide. In some embodiments, the second PRAME epitope sequence consists of from 8 to 30, from 9 to 29, from 10 to 28, from 11 to 27, from 12 to 26, from 13 to 25, from 14 to 24, or from 15 to 23 consecutive amino acids from the full length PRAME polypeptide.

[0371] In some embodiments, the first amino acid sequence comprises the first PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first PRAME epitope sequence from the full length PRAME polypeptide. In some embodiments, the second amino acid sequence comprises the second PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second PRAME epitope sequence from the full length PRAME polypeptide.

[0372] In some embodiments, the multi epitopic polypeptide does not comprise more than 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or more consecutive amino acids from the full-length PRAME polypeptide.

[0373] In some embodiments, the multiepitopic polypeptide comprises a first PRAME epitope sequence. In some embodiments, the first PRAME epitope sequence is operably linked to a second PRAME epitope sequence. In some embodiments, the first PRAME epitope sequence and the second PRAME epitope sequence are the same. In some embodiments, the first PRAME epitope sequence and second PRAME epitope sequence are different. In some embodiments, the first PRAME epitope sequence and second PRAME epitope sequence are presentable by different HLA alleles. In some embodiments, the first PRAME epitope sequence and second PRAME epitope sequence are presented by different HLA alleles. In some embodiments, the first PRAME epitope sequence and second PRAME epitope sequence are predicted to bind todifferent HLA alleles. In some embodiments, the first PRAME epi...

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A method of treating a subject with a disease or condition comprising administering to the subject a therapy comprising (i) a multiepitopic polypeptide, (ii) a recombinant nucleic acid encoding the multiepitopic polypeptide, or (iii) a cell comprising the multiepitopic polypeptide or the recombinant nucleic acid encoding the multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope.

2. The method of claim 1, wherein the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA-B*08:01.

3. The method of claim 1 or 2, wherein the epitope sequence presentable by HLA-B*08:01 comprises a sequence of any one of SEQ ID NOs: 6, 14 and 32.

4. The method of any one of claims 1-3, wherein the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA- A*03:01.

5. The method of any one of claims 1-4, wherein the epitope sequence presentable by HLA- A*03:01 comprises a sequence of any one of SEQ ID NOs: 8, 22, and 26.

6. The method of any one of claims 1-5, wherein the first PRAME epitope sequence or the second PRAME epitope sequence comprises an epitope sequence presentable by HLA- A*01:01.

7. The method of any one of claims 1-6, wherein the epitope sequence presentable by HLA- A*01:01 comprises a sequence of SEQ ID NO: 28 or 30.

8. The method of any one of claims 1-7, wherein the common C-allele epitope is presentable by an HLA-C.

9. The method of claim 8, wherein the HLA-C is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02.

10. The method of claim 8 or 9, wherein the common C-allele epitope comprises a sequence of SEQ ID NO: 24.

11. The method of any one of claims 1-10, wherein the multiepitopic polypeptide further comprises a linker for analytics.

12. The method of claim 11, wherein the linker for analytics comprises a sequence of SEQ ID NO: 18.

13. The method of any one of claims 1-12, wherein presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the therapy is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

14. The method of any one of claims 1-13, further comprising administering to the subject a T-cell receptor (TCR) or a recombinant nucleic acid encoding the TCR.

15. The method of any one of claims 1-14, wherein the first PRAME epitope sequence and the second PRAME epitope sequence is separated by a linker.

16. The method of any one of claims 1-14, wherein the first PRAME amino acid sequence is the first epitope sequence and / or the second PRAME amino acid sequence is the second epitope sequence.

17. The method of any one of claims 1-15, wherein the first PRAME amino acid sequence consists of the first epitope sequence, and / or the second PRAME amino acid sequence consists of the second epitope sequence.

18. The method of any one of claims 1-17, wherein the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length PRAME polypeptide.

19. The method of any one of claims 1-18, wherein the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length PRAME polypeptide.

20. The method of any one of claims 1-19, wherein the first PRAME amino acid sequence and the second PRAME amino acid sequence is separated by a linker.

21. The method of any one of claims 1-20, wherein the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one or more residues flanking the N- terminus or the C-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide.

22. The method of any one of claims 1-21, wherein the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second PRAME epitope sequence from the full- length PRAME polypeptide.

23. The method of any one of claims 1-22, wherein the multiepitopic polypeptide does not comprise more than 15 or more consecutive amino acids from the full-length PRAME polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length PRAME polypeptide.

24. The method of any one of claims 14-23, wherein the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) the first or the second PRAME epitope sequence, and (ii) a human MHC encoded by an HLA allele.

25. A method of treating a subject with a disease or condition comprising administering to the subject (a) a PRAME polypeptide, (b) a recombinant nucleic acid encoding the PRAME polypeptide, or (c) a cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide, wherein the PRAME polypeptide comprises a multiepitopic polypeptide that does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, wherein the subject has been previously administered a T-cell receptor (TCR) or a recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) the first or the second PRAME epitope sequence, and (ii) a human MHC encoded by an HLA allele.

26. A method of treating a subject with a disease or condition comprising administering to the subject a T-cell receptor (TCR) or a recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) a PRAME epitope sequence, and (ii) a human MHC encoded by an HLA allele, wherein the subject has been previously administered (a) a PRAME polypeptide, (b) a recombinant nucleic acid encoding the PRAME polypeptide, or (c) a cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide, wherein the PRAME polypeptide comprises a multiepitopic polypeptide that does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C- allele epitope.

27. A method of treating a subject with a disease or condition comprising,(a) administering to the subject (i) a PRAME polypeptide, (ii) a recombinant nucleic acid encoding the PRAME polypeptide, or (iii) a cell comprising the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide, wherein the PRAME polypeptide comprises a multiepitopic polypeptide that does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence,wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope; and(b) administering to the subject a TCR or a recombinant nucleic acid encoding the TCR, wherein the TCR recognizes and binds to a peptide: MHC complex, the peptide: MHC complex comprising (i) the first or the second PRAME epitope sequence, and (ii) a human MHC encoded by an HLA allele.

28. The method of claim 27, wherein administering in (a) is performed concurrently with administering in (b).

29. The method of claim 27, wherein administering in (a) is prior to administering in (b).

30. The method of claim 27, wherein administering in (a) is subsequent to administering in (b).

31. The method of any one of claims 25, 27 and 30, wherein the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the TCR or the recombinant nucleic acid encoding the TCR.

32. The method of any one of claims 26, 27 and 29, wherein the TCR or the recombinant nucleic acid encoding the TCR is administered at least 1 day, 2 days, 5 days, 10 days, 20 days, 30 days, 1 month, 2 months, 3 months, 6 months, 1 year, 2 years or more after the subject has been administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide.

33. The method of any one of claims 14-32, wherein the T-cell receptor (TCR) or the recombinant nucleic acid encoding the TCR is expressed by an immune cell.

34. The method of any one of claims 14-33, wherein the TCR is a soluble TCR.

35. The method of any one of claims 14-34, further comprising administering two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs, and wherein the two or more different TCRs comprise a first TCR and a second TCR.

36. The method of claim 35, wherein the two or more different TCRs are expressed on surface of two different immune cells.

37. The method of claim 35 or 36, wherein the first TCR and the second TCR bind to different peptide: MHC complexes, each peptide: MHC complex comprising (i) an epitope sequence and (ii) a human MHC encoded by an HLA allele.

38. The method of any one of claims 1-37, wherein each of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope.

39. The method of any one of claims 1-37, wherein the first PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02.

40. The method of any one of claims 1-37, wherein the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope, and the first PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA-A*02:01, an epitope sequence presentable by HLA-B*07:02.

41. The method of any one of claims 1-40, wherein the PRAME polypeptide further comprises one or more additional PRAME epitope sequences.

42. The method of claim 41, wherein the one or more additional PRAME epitope sequences comprise one or more epitope sequences selected from the group consisting of an epitopesequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA- A*02:01, an epitope sequence presentable by HLA-B*07:02, and any combination thereof.

43. The method of claim 42, wherein the epitope sequence presentable by HLA-A*24:02 comprises a sequence of any one of SEQ ID NOs: 4, 10, 58, and 59.

44. The method of claim 42 or 43, wherein the epitope sequence presentable by HLA- A*02:01 comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

45. The method of any one of claims 42-44, wherein the epitope sequence presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

46. The method of any one of claims 35-45, wherein the two or more different TCRs or recombinant nucleic acids encoding the two or more different TCRs are administered separately or co-administered in a same mixture.

47. The method of any one of claims 35-46, wherein(a) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 16 and an MHC encoded by an HLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele;(b) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 16 and an MHC encoded by an HLA-A*02:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele;(c) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 12 and an MHC encoded by an HLA-B*07:02 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of any one of SEQ ID NOs: 4, 10, 58, and 59 and an MHC encoded by an HLA-A*24:02 allele;(d) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complexcomprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26 and an MHC encoded by an HLA-A*03:01 allele;(e) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele;(f) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32, and an MHC encoded by an HLA-B*08:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele;(g) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele;(h) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26, and an MHC encoded by an HLA-A*03:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele; or(i) the first TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30 and an MHC encoded by an HLA-A*01:01 allele and the second TCR binds to a peptide: MHC complex comprising an epitope sequence of SEQ ID NO: 24 and an MHC encoded by an HLA-C allele.

48. The method of any one of claims 42-47, wherein the PRAME epitope sequence comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

49. The method of claim 48, wherein the HLA allele is an HLA-A*02:01 allele.

50. The method of any one of claims 42-49, wherein the PRAME epitope sequence comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

51. The method of claim 50, wherein the HLA allele is an HLA-B*07:02 allele.

52. The method of any one of claims 42-51, wherein the PRAME epitope sequence comprises a sequence of SEQ ID NO: 4, SEQ ID NO: 10, SEQ ID NO: 58, SEQ ID NO: 59.

53. The method of claim 52, wherein the HLA allele is an HLA-A*24:02 allele.

54. The method of any one of claims 25-53, wherein the PRAME epitope sequence comprises a sequence of SEQ ID NO: 6, SEQ ID NO: 14, or SEQ ID NO: 32.

55. The method of claim 54, wherein the HLA allele is an HLA-B*08:01 allele.

56. The method of any one of claims 25-55, wherein the PRAME epitope sequence comprises a sequence of SEQ ID NO: 8, SEQ ID NO: 22, or SEQ ID NO: 26.

57. The method of claim 56, wherein the HLA allele is an HLA-A*03:01 allele.

58. The method of any one of claims 25-57, wherein the PRAME epitope sequence comprises a sequence of SEQ ID NO: 20, SEQ ID NO: 28 or SEQ ID NO: 30.

59. The method of claim 58, wherein the HLA allele is an HLA-A*01:01.

60. The method of any one of claims 25-59, wherein the PRAME epitope sequence comprises a sequence of SEQ ID NO: 24.

61. The method of claim 60, wherein the HLA allele is an HLA-C allele.

62. The method of claim 61, wherein the HLA-C allele is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:

02.

63. The method of any one of claims 25-62, wherein the first and second PRAME epitope sequences are separated by one or more linker sequences.

64. The method of claim 63, wherein the one or more linker sequences are selected from the group consisting of SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 21, 23, 25, 27, 29, 31, 33, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, and any combination thereof.

65. The method of any one of claims 25-64, wherein antigen presenting cells (APCs) of the subject administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide comprising the multiepitopic polypeptide present more of a PRAME epitope sequence as a peptide: MHC complex compared to the APCs of a subjectadministered a full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

66. The method of any one of claims 25-65, wherein T cells of the subject administered the multiepitopic polypeptide or a recombinant nucleic acid encoding the multiepitopic polypeptide exhibit increased expansion compared to T cells of a subject administered a full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

67. The method of any one of claims 25-66, wherein the first PRAME amino acid sequence is the first PRAME epitope sequence and / or the second PRAME amino acid sequence is the second PRAME epitope sequence.

68. The method of any one of claims 25-67, wherein the first PRAME amino acid sequence consists of the first PRAME epitope sequence, and / or the second PRAME amino acid sequence consists of the second PRAME epitope sequence.

69. The method of any one of claims 25-68, wherein the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length PRAME polypeptide.

70. The method of any one of claims 25-68, wherein the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length PRAME polypeptide.

71. The method of any one of claims 25-70, wherein the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one or more residues flanking the N- terminus or the C-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide.

72. The method of any one of claims 25-71, wherein the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide.

73. The method of any one of claims 25-72, wherein the multi epitopic polypeptide does not comprise more than 15 or more consecutive amino acids from the full-length PRAME polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length PRAME polypeptide.

74. The method of any one of claims 25-73, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles.

75. The method of any one of claims 25-74, wherein a first PRAME epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) binds to or is predicted to bind to a second HLA allele with a KDof more than 500 nM.

76. The method of any one of claims 25-75, wherein the multiepitopic polypeptide comprises a first PRAME epitope sequence, operably linked to a second PRAME epitope sequence, operably linked to a third PRAME epitope sequence.

77. The method of claim 76, wherein the PRAME polypeptide further comprises one or more epitope sequences selected from the group consisting of an epitope presentable by HLA- A*02:01, an epitope presentable by HLA-B*07:02, and an epitope presentable by HLA- A*24:02.

78. The method of claim 77, wherein the epitope presentable by HLA-A*02:01 comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

79. The method of claim 77, wherein the epitope presentable by HLA-B*07:02 comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

80. The method of claim 77, wherein the epitope presentable by HLA-A*24:02 comprises a sequence of any one of SEQ ID NOs: 4, 10, 58, and 59.

81. The method of any one of claims 25-80, wherein the subject does not express an HLA allele that recognizes each PRAME epitope sequence of the multiepitopic polypeptide.

82. The method of any one of claims 25-81, wherein the subject only expresses HLA alleles that recognize a subset of PRAME epitope sequences of the multi epitopic polypeptide.

83. The method of any one of claims 25-82, wherein the multiepitopic polypeptide comprises, from N-terminus to C-terminus, a first epitope sequence presentable by HLA- A*24:02, a first epitope sequence presentable by HLA-B*08:01, a first epitope sequence presentable by HLA-A*03:01, a second epitope sequence presentable by HLA-A*24:02, a first epitope sequence presentable by HLA-B*07:02, a second epitope sequence presentable by HLA-B*08:01, a first epitope sequence presentable by HLA-A*02:01, afirst epitope sequence presentable by HLA-A*01:01, a second epitope sequence presentable by HLA-A*03:01, a common C-allele epitope sequence, a third epitope sequence presentable by HLA-A*03:01, a second epitope sequence presentable by HLA- A*01:01, a third epitope sequence presentable by HLA-A*01:01, and a third epitope sequence presentable by HLA-B*08:01.

84. The method of any one of claims 25-82, wherein the multiepitopic polypeptide comprises, from N-terminus to C-terminus, a first epitope sequence presentable by HLA- A* 03: 01, an epitope sequence presentable by HLA-A*01:01, an epitope sequence presentable by HLA-B*07:02, a common C-allele epitope sequence, a first epitope sequence presentable by HLA-A*24:02, an epitope sequence presentable by HLA- A*02:01, a second epitope sequence presentable by HLA-A*24:02, a first epitope sequence presentable by HLA-B*08:01, and a second epitope sequence presentable by HLA-B*08:01.

85. The method of claim 83 or 84, wherein each epitope sequence presentable by HLA- A*24:02 comprises a sequence of any one of SEQ ID NOs: 4, 10, 58, and 59.

86. The method of claim 83 or 84, wherein each epitope sequence presentable by HLA- B*08:01 comprises a sequence of SEQ ID NO: 6, 14, or 32.

87. The method of claim 83 or 84, wherein each epitope sequence presentable by HLA- A*03:01 comprises a sequence of SEQ ID NO: 8, 22, or 26.

88. The method of claim 83 or 84, wherein each epitope sequence presentable by HLA- B*07:02 comprises a sequence of SEQ ID NO: 12 or SEQ ID NO: 57.

89. The method of claim 83 or 84, wherein the epitope sequence presentable by HLA- A*02:01 comprises a sequence of SEQ ID NO: 16 or SEQ ID NO: 56.

90. The method of claim 83 or 84, wherein each epitope sequence presentable by HLA- A*01:01 comprises a sequence of SEQ ID NO: 20, 28, 30.

91. The method of claim 83 or 84, wherein the common C-allele epitope sequence comprises a sequence of SEQ ID NO: 24.

92. The method of any one of claims 83-91, wherein the multiepitopic polypeptide comprises, at the N-terminal end, a Secretory (Sec) domain.

93. The method of claim 92, wherein the Sec domain comprises a sequence of SEQ ID NO:1.

94. The method of claim 92 or 93, wherein the Sec domain is operably linked to the multiepitopic polypeptide via a linker.

95. The method of claim 94, wherein the linker comprises a sequence of SEQ ID NO: 2 or 37.

96. The method of any one of claims 83-95, wherein the multi epitopic polypeptide comprises, at the C-terminal end, an MHC Class I Trafficking Signal (MITD) domain.

97. The method of claim 96, wherein the MITD domain comprises a sequence of SEQ ID NO: 34.

98. The method of claim 96 or 97, wherein the MITD domain is operably linked to the multiepitopic polypeptide via a linker.

99. The method of claim 98, wherein the linker comprises a sequence of SEQ ID NO: 2 or 37.

100. The method of any one of claims 83-99, wherein each of the epitope sequences is flanked by one or more cleavable linker sequences.

101. The method of claim 100, wherein the one or more cleavable linker sequence is selected from the group consisting of SEQ ID NOs: 3, 5, 7, 9, 11, 13, 15, 17, 21, 23, 25, 27, 29, 31, 33, 39, 40, 41, 42, 43, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, and any combination thereof.

102. The method of any one of claims 83 and 85-101, wherein the multiepitopic polypeptide comprises a sequence having at least 80% identity to any one of SEQ ID NOs: 35, 36, and 38.

103. The method of any one of claims 84-102, wherein the multi epitopic polypeptide comprises a sequence having at least 80% identity to SEQ ID NO: 55.

104. The method of any one of claims 25-103, wherein the recombinant nucleic acid encoding the PRAME polypeptide comprises one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

105. The method of claim 104, wherein the recombinant nucleic acid encoding the PRAME polypeptide comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

106. The method of claim 104 or 105, wherein the recombinant nucleic acid encoding the PRAME polypeptide comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

107. The method of any one of claims 104-106, wherein the recombinant nucleic acid encoding the PRAME polypeptide comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

108. The method of any one of claims 104-107, wherein the recombinant nucleic acid encoding the multi epitopic polypeptide comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*07:02, a sequence encoding a second epitope sequence presentable by HLA- B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*02:01, asequence encoding a first epitope sequence presentable by HLA-A*01:01, a sequence encoding a second epitope sequence presentable by HLA-A*03:01, a sequence encoding a common C-allele epitope sequence, a sequence encoding a third epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*01:01, a sequence encoding a third epitope sequence presentable by HLA-A*01:01, and a sequence encoding a third epitope sequence presentable by HLA-B*08:01.

109. The method of any one of claims 104-108, wherein the recombinant nucleic acid encoding the multi epitopic polypeptide comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding an epitope sequence presentable by HLA-A*01:01, a sequence encoding an epitope sequence presentable by HLA-B*07:02, a sequence encoding a common C-allele epitope sequence, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding an epitope sequence presentable by HLA-A*02:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, and a sequence encoding a second epitope sequence presentable by HLA-B*08:01.

110. The method of claim 108 or 109, wherein each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence of any one of SEQ ID NOs: 64, 70, 97, 103, 127, 133, 154, 176, 192, 197, 242, and 244.

111. The method of claim 108 or 109, wherein each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence of any one of SEQ ID NOs: 66, 74, 92, 99, 107, 124, 129, 136, 151, 155, 160, 174, 179, 191, 194, 198, 207, 229, 231, and 233.

112. The method of claim 108 or 109, wherein each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence of any one of SEQ ID NOs: 68, 82, 86, 101, 114, 118, 131, 142, 146, 156, 166, 169, 177, 184, 186, 195, 201, 203, and 218.

113. The method of claim 108 or 109, wherein each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence of any one of SEQ ID NOs: 105, 134, 158, 105, 158, 222, and 240.

114. The method of claim 108 or 109, wherein the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence of any one of SEQ ID NOs: 76, 109, 138, 162, 181, 199, and 238.

115. The method of claim 108 or 109, wherein each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence of any one of SEQ ID NOs: 84, 116, 144, 167, 202, and 224.

116. The method of claim 108 or 109, wherein the sequence encoding a common C-allele epitope sequence comprises a sequence of SEQ ID NO: 24.

117. The method of any one of claims 108-116, wherein the recombinant nucleic acid comprises, at the 5 ’end, a sequence encoding a Secretory (Sec) domain.

118. The method of claim 117, wherein the sequence encoding a Sec domain comprises a sequence of SEQ ID NO: 61.

119. The method of claim 117 or 118, wherein the sequence encoding the Sec domain is operably linked to the recombinant nucleic via a sequence encoding a linker.

120. The method of claim 119, wherein the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

121. The method of any one of claims 108-120, wherein the recombinant nucleic acid comprises, at the 3 ’-end, a sequence encoding an MHC Class I Trafficking Signal (MITD) domain.

122. The method of claim 121, wherein the sequence encoding the MITD domain comprises a sequence of SEQ ID NO: 95 or 216.

123. The method of claim 121 or 122, wherein the sequence encoding the MITD domain is operably linked to the recombinant nucleic acid via a sequence encoding a linker.

124. The method of claim 123, wherein the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

125. The method of any one of claims 108-124, wherein each of the sequences encoding an epitope sequence is flanked by a sequence encoding a cleavable linker.

126. The method of claim 125, wherein the sequence encoding the cleavable linker sequence is selected from the group consisting of SEQ ID NOs: 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159,161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof.

127. The method of any one of claims 108 and 110-126, wherein the recombinant nucleic acid comprises a sequence having at least 80% identity to any one of SEQ ID NOs: 247-253, 255, 273, 274, and 293.

128. The method of any one of claims 109-127, wherein the recombinant nucleic acid comprises a sequence having at least 80% identity to SEQ ID NO: 254.

129. The method of any one of claims 104-128, wherein the recombinant nucleic acid is codon-optimized.

130. The method of any one of claims 104-129, wherein the recombinant nucleic acid is an RNA.

131. The method of any one of claims 1-129, wherein the subject expresses more of the PRAME epitope when administered with the codon-optimized recombinant nucleic acid than administered with wild-type recombinant nucleic acid.

132. The method of any one of claims 14-131, wherein the TCR comprises a TCR beta chain construct and a TCR alpha chain construct, wherein the TCR beta chain construct comprises a complementarity determining region 3 (CDR3) having an amino acid sequence set forth in SEQ ID NO: 262.

133. The method of claim 132, wherein the TCR beta chain construct comprises a variable region having an amino acid sequence with at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 264 or 271.

134. The method of claim 132 or 133, wherein the TCR beta chain construct comprises a complementarity determining region 1 (CDR1) having an amino acid sequence set forth in SEQ ID NO: 260 and a complementarity determining region 2 (CDR2) having an amino acid sequence set forth in SEQ ID NO: 261.

135. The method of any one of claims 132-134, wherein the TCR alpha chain construct comprises a CDR1, a CDR2, and a CDR3, wherein the CDR1 has an amino acid sequence set forth in SEQ ID NO: 257, the CDR2 has an amino acid sequence set forth in SEQ ID NO: 258, and the CDR3 has an amino acid sequence set forth in SEQ ID NO: 259.

136. The method of any one of claims 132-135, wherein the TCR alpha chain construct comprises a variable region having an amino acid sequence having at least 80% sequence identity to an amino acid sequence set forth in SEQ ID NO: 263 or 269.

137. The method of any one of claims 132-136, wherein the TCR comprises: (a) a beta chain having an amino acid sequence set forth in SEQ ID NO: 265, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 265, and (b) an alpha chain having an amino acid sequence set forth in SEQ ID NO: 294, or an amino acid sequence that is at least 80% identical to SEQ ID NO: 294.

138. A recombinant nucleic acid encoding a TCR comprising:(a) a TCR beta chain construct, and(b) a TCR alpha chain construct;wherein the TCR binds to a peptide: MHC complex, the peptide: MHC complex comprising(i) a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 6, 14 and 32, and a human MHC encoded by the HLA-B*08:01 allele;(ii) a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 8, 22, and 26, and a human MHC encoded by the HLA-A*03:01 allele;(iii) a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence according to SEQ ID NO: 28 or 30, and a human MHC encoded by the HLA-A*01:01 allele; or(iv) a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence according to SEQ ID NO: 24, and a human MHC encoded by an HLA-C allele.

139. The recombinant nucleic acid of claim 138, wherein the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 6, 14 and 32, and a human MHC encoded by the HLA-B*08:01 allele.

140. The recombinant nucleic acid of claim 139, wherein the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to any one of SEQ ID NOs: 6, 14 and 32.

141. The recombinant nucleic acid of claim 138, wherein the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of any one of SEQ ID NOs: 8, 22, and 26, and a human MHC encoded by the HLA-A*03:01 allele.

142. The recombinant nucleic acid of claim 141, wherein the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to any one of SEQ ID NOs: 8, 22, and 26.

143. The recombinant nucleic acid of claim 138, wherein the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence according to SEQ ID NO: 28 or 30, and a human MHC encoded by the HLA-A*01:01 allele.

144. The recombinant nucleic acid of claim 143, wherein the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NOs: 28 or 30.

145. The recombinant nucleic acid of claim 138, wherein the peptide: MHC complex comprises a PRAME epitope sequence having at least 7 consecutive amino acids of a sequence of SEQ ID NO: 24, and a human MHC encoded by the HLA-C allele.

146. The recombinant nucleic acid of claim 145, wherein the HLA-C allele is selected from the group consisting of HLA-C*04:01, HLA-C*06:02, HLA-C*07:01, HLA-C*03:04, and HLA-C*08:02.

147. The recombinant nucleic acid of claim 145 or 146, wherein the peptide: MHC complex comprises the PRAME epitope sequence having a sequence according to SEQ ID NO: 24.

148. A cell comprising the recombinant nucleic acid of any one of claims 138-147.

149. The cell of claim 148, wherein the cell is a T cell.

150. The cell of claim 148 or 149, wherein, upon binding of the TCR to the peptide:MHC complex, the cell produces a proinflammatory cytokine.

151. The cell of claim 150, wherein the proinflammatory cytokine is IFN-y, IL-2, TNF-a, IL- 6, or IL- 17.

152. The cell of any one of claims 148-151, wherein, upon binding of the TCR to the peptide:MHC complex, cytotoxicity of the cell against target cells is increased by 25%, 50%, 100%, 150%, 200%, or more compared to an otherwise identical cell not having a TCR specific for the peptide:MHC complex.

153. A recombinant nucleic acid encoding a multiepitopic polypeptide, wherein the multiepitopic polypeptide does not comprise a full-length PRAME polypeptide and comprises a first PRAME amino acid sequence comprising a first PRAME epitope sequence and a second PRAME amino acid sequence comprising a second PRAME epitope sequence, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are different, and wherein at least one of the first PRAME epitope sequence and the second PRAME epitope sequence comprises an epitope sequence selected from the group consisting of an epitope sequence presentable by HLA-B*08:01, an epitope sequence presentable by HLA-A*03:01, an epitope sequence presentable by HLA-A*01:01, and a common C-allele epitope.

154. The recombinant nucleic acid of claim 153, wherein presentation of the first and / or second PRAME epitope sequence as a peptide:MHC complex by antigen presenting cells (APCs) of the subject administered the PRAME polypeptide or the recombinant nucleic acid encoding the PRAME polypeptide is higher than the presentation of the first and / or second PRAME epitope sequence as the peptide:MHC complex by the APCs of a subject administered the full-length PRAME polypeptide or a recombinant nucleic acid encoding the full-length PRAME polypeptide.

155. The recombinant nucleic acid of claim 153 or 154, wherein the first PRAME amino acid sequence is the first epitope sequence and / or the second PRAME amino acid sequence is the second epitope sequence.

156. The recombinant nucleic acid of any one of claims 153-155, wherein the first PRAME amino acid sequence consists of the first epitope sequence, and / or the second PRAME amino acid sequence consists of the second epitope sequence.

157. The recombinant nucleic acid of any one of claims 153-156, wherein the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 7 to 12 consecutive amino acids from the full-length PRAME polypeptide.

158. The recombinant nucleic acid of any one of claims 153-156, wherein the first PRAME epitope sequence and / or the second PRAME epitope sequence consists of from 13 to 25 consecutive amino acids from the full-length PRAME polypeptide.

159. The recombinant nucleic acid of any one of claims 153-158, wherein the first PRAME epitope sequence and the second PRAME epitope sequence is separated by a linker.

160. The recombinant nucleic acid of any one of claims 153, 154 and 157-159, wherein the first PRAME amino acid sequence comprises the first PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the first PRAME epitope sequence from the full-length PRAME polypeptide.

161. The recombinant nucleic acid of any one of claims 153, 154 and 157-160, wherein the second PRAME amino acid sequence comprises the second PRAME epitope sequence and one or more residues flanking the N-terminus or the C-terminus of the second PRAME epitope sequence from the full-length PRAME polypeptide.

162. The recombinant nucleic acid of any one of claims 153-161, wherein the multiepitopic polypeptide does not comprise more than 12 or more consecutive amino acids from the full-length PRAME polypeptide, or the multiepitopic polypeptide does not comprise more than 25 or more consecutive amino acids from the full-length PRAME polypeptide.

163. The recombinant nucleic acid of any one of claims 153-162, wherein the multiepitopic polypeptide further comprises a Secretory (Sec) sequence at the N-terminus of the multiepitopic polypeptide.

164. The recombinant nucleic acid of claim 163, wherein the Sec sequence comprises a sequence of SEQ ID NO: 1.

165. The recombinant nucleic acid of any one of claims 153-164, wherein the Sec sequence is operably linked to the multiepitopic polypeptide via a linker.

166. The recombinant nucleic acid of claim 165, wherein the linker comprises a sequence of SEQ ID NO: 2 or 37.

167. The recombinant nucleic acid of any one of claims 153-166, wherein the multiepitopic polypeptide further comprises an MHC class I trafficking signal (MITD) sequence at the C-terminus of the multiepitopic polypeptide.

168. The recombinant nucleic acid of claim 167, wherein the MITD sequence comprises a sequence of SEQ ID NO: 34.

169. The recombinant nucleic acid of claim 167, wherein the multi epitopic polypeptide is operably linked to the MITD sequence via a linker.

170. The recombinant nucleic acid of claim 169, wherein the linker comprises a sequence of SEQ ID NO: 2 or 37.

171. The recombinant nucleic acid of any one of claims 153-170, wherein the multiepitopic polypeptide comprises at least 3, 4, 5, or more different PRAME epitope sequences.

172. The recombinant nucleic acid of any one of claims 153-171, wherein the first PRAME epitope sequence and the second PRAME epitope sequence are presentable by different HLA alleles, are presented by different HLA alleles, bind to different HLA alleles, are predicted to bind to different HLA alleles, or are predicted to be presented by different HLA alleles.

173. The recombinant nucleic acid of any one of claims 153-172, wherein a first PRAME epitope sequence (i) binds to or is predicted to bind to a first HLA allele with a KD of less than 100 nM and (ii) binds to or is predicted to bind to a second HLA allele with a KDof more than 500 nM.

174. The recombinant nucleic acid of any one of claims 153-173, wherein each of the sequences encoding the PRAME epitope sequences is flanked by one or more sequences encoding a cleavable linker sequence.

175. The recombinant nucleic acid of claim 174, wherein the one or more sequences encoding a cleavable linker sequence is selected from the group consisting of SEQ ID NOs: 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159, 161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof.

176. The recombinant nucleic acid of claim 171, wherein the multi epitopic polypeptide comprises a first PRAME epitope sequence, operably linked to a second PRAME epitope sequence, operably linked to a third PRAME epitope sequence.

177. The recombinant nucleic acid of any one of claims 153-176, wherein the recombinant nucleic acid comprises one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

178. The recombinant nucleic acid of claim 177, wherein the recombinant nucleic acid comprises one or more copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

179. The recombinant nucleic acid of claim 177 or 178, wherein the recombinant nucleic acid comprises two, three, four, or five copies of one or more sequences selected from the group consisting of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179, 181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

180. The recombinant nucleic acid of any one of claims 177-179, wherein the recombinant nucleic acid comprises two, three, four, or five copies of each sequence of SEQ ID NOs: 64, 66, 68, 70, 72, 74, 76, 80, 82, 84, 86, 88, 90, 92, 97, 99, 101, 103, 105, 107, 109, 112, 114, 116, 118, 120, 122, 124, 127, 129, 131, 133, 134, 136, 138, 140, 142, 144, 146, 148, 149, 151, 154, 155, 156, 158, 160, 162, 164, 166, 167, 169, 171, 172, 174, 176, 177, 179,181, 184, 186, 188, 189, 191, 192, 194, 195, 197, 198, 199, 200, 201, 202, 203, 204, 206, 207, 218, 220, 222, 224, 229, 231, 233, 235, and 237.

181. The recombinant nucleic acid of any one of claims 177-180, wherein the recombinant nucleic acid comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding a second epitope sequence presentable by HLA- A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*07:02, a sequence encoding a second epitope sequence presentable by HLA-B*08:01, a sequence encoding a first epitope sequence presentable by HLA-A*02:01, a sequence encoding a first epitope sequence presentable by HLA-A*01:01, a sequence encoding a second epitope sequence presentable by HLA-A*03:01, a sequence encoding a common C-allele epitope sequence, a sequence encoding a third epitope sequence presentable by HLA- A*03:01, a sequence encoding a second epitope sequence presentable by HLA-A*01:01, a sequence encoding a third epitope sequence presentable by HLA-A*01:01, and a sequence encoding a third epitope sequence presentable by HLA-B*08:01.

182. The recombinant nucleic acid of any one of claims 177-180, wherein the recombinant nucleic acid comprises, from 5 ’-end to 3 ’-end, a sequence encoding a first epitope sequence presentable by HLA-A*03:01, a sequence encoding an epitope sequence presentable by HLA-A*01:01, a sequence encoding an epitope sequence presentable by HLA-B*07:02, a sequence encoding a common C-allele epitope sequence, a sequence encoding a first epitope sequence presentable by HLA-A*24:02, a sequence encoding an epitope sequence presentable by HLA-A*02:01, a sequence encoding a second epitope sequence presentable by HLA-A*24:02, a sequence encoding a first epitope sequence presentable by HLA-B*08:01, and a sequence encoding a second epitope sequence presentable by HLA-B*08:01.

183. The recombinant nucleic acid of claim 181 or 182, wherein each sequence encoding an epitope sequence presentable by HLA-A*24:02 comprises a sequence selected from the group consisting of SEQ ID NOs: 64, 70, 97, 103, 127, 133, 154, 176, 192, 197, 242, and 244.

184. The recombinant nucleic acid of claim 181 or 182, wherein each sequence encoding an epitope sequence presentable by HLA-B*08:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 66, 74, 92, 99, 107, 124, 129, 136, 151, 155, 160, 174, 179, 191, 194, 198, 207, 229, 231, and 233.

185. The recombinant nucleic acid of claim 181 or 182, wherein each sequence encoding an epitope sequence presentable by HLA-A*03:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 68, 82, 86, 101, 114, 118, 131, 142, 146, 156, 166, 169, 177, 184, 186, 195, 201, 203, and 218.

186. The recombinant nucleic acid of claim 181 or 182, wherein each sequence encoding an epitope sequence presentable by HLA-B*07:02 comprises a sequence selected from the group consisting of SEQ ID NOs: 105, 134, 158, 105, 158, 222, 240.

187. The recombinant nucleic acid of claim 181 or 182, wherein the sequence encoding an epitope sequence presentable by HLA-A*02:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 76, 109, 138, 162, 181, 199, and 238.

188. The recombinant nucleic acid of claim 181 or 182, wherein each sequence encoding an epitope sequence presentable by HLA-A*01:01 comprises a sequence selected from the group consisting of SEQ ID NOs: 80, 88, 90, 112, 120, 122, 140, 148, 149, 164, 171, 172, 188, 189, 200, 204, 206, 220, 235, and 237.

189. The recombinant nucleic acid of claim 181 or 182, wherein the sequence encoding a common C-allele epitope sequence comprises a sequence selected from the group consisting of SEQ ID NOs: 84, 116, 144, 167, 202, and 224.

190. The recombinant nucleic acid of any one of claims 181-189, wherein the recombinant nucleic acid comprises, at the 5 ’end, a sequence encoding a Secretory (Sec) domain.

191. The recombinant nucleic acid of claim 190, wherein the sequence encoding a Sec domain comprises a sequence of SEQ ID NO: 61.

192. The recombinant nucleic acid of claim 190 or 191, wherein the sequence encoding the Sec domain is operably linked to the recombinant nucleic via a sequence encoding a linker.

193. The recombinant nucleic acid of claim 192, wherein the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

194. The recombinant nucleic acid of any one of claims 181-193, wherein the recombinant nucleic acid comprises, at the 3 ’-end, a sequence encoding an MHC Class I Trafficking Signal (MITD) domain.

195. The recombinant nucleic acid of claim 194, wherein the sequence encoding the MITD domain comprises a sequence of SEQ ID NO: 95 or 216.

196. The recombinant nucleic acid of claim 194 or 195, wherein the sequence encoding the MITD domain is operably linked to the recombinant nucleic acid via a sequence encoding a linker.

197. The recombinant nucleic acid of claim 196, wherein the sequence encoding the linker comprises a sequence of any one of SEQ ID NOs: 62, 94, 208, and 215.

198. The recombinant nucleic acid of any one of claims 181-197, wherein each of the sequences encoding an epitope sequence is flanked by one or more sequences encoding a cleavable linker.

199. The recombinant nucleic acid of claim 198, wherein the one or more sequences encoding the cleavable linker is selected from the group consisting of SEQ ID NOs: 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 89, 91, 93, 96, 98, 100, 102, 104, 106, 108, 110, 111, 113, 115, 117, 119, 121, 123, 125, 126, 128, 130, 132, 135, 137, 139, 141, 143, 145, 147, 150, 152, 152, 157, 159, 161, 163, 168, 170, 173, 175, 178, 180, 182, 183, 185, 187, 193, 196, 205, 217, 219, 221, 223, 225, 226, 227, 228, 230, 232, 234, 236, and any combination thereof.

200. The recombinant nucleic acid of any one of claims 181 and 183-199, wherein the recombinant nucleic acid comprises a sequence having at least 80% identity to any one of SEQ ID NOs: 247-253, 255, 273, 274, and 293.

201. The recombinant nucleic acid of any one of claims 182-199, wherein the recombinant nucleic acid comprises a sequence having at least 80% identity to SEQ ID NO:

254.

202. A recombinant nucleic acid having at least 60% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 245-253, 254-256, 273, 274, and 293.

203. A recombinant polypeptide having at least 80% sequence identity to a sequence selected from the group consisting of SEQ ID NOs: 35, 36, 38, 55, and 60.

204. A polypeptide encoded by the recombinant nucleic acid of any one of claims 147-195.

205. A pharmaceutical composition comprising the recombinant nucleic acid of any one of claims 153-202 or the polypeptide of claim 203 or 204, and a pharmaceutically acceptable carrier.

206. The recombinant nucleic acid of any one of claims 153-202, the polypeptide of claim 203 or 204, or the pharmaceutical composition of claim 205 for use in therapy.

207. Use of the recombinant nucleic acid of any one of claims 153-202, the polypeptide of claim 203 or 204, or the pharmaceutical composition of claim 205, in the manufacture of a medicament for the treatment of cancer in a subject in need thereof.

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