Methods and compositions for cancer treatment using recombinant polypeptides

Abstract

Disclosed hereopin are methods for the treatment of cancer in a human subject comprising administration of a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope. Peptides recogniz

Description

[0001] METHODS AND COMPOSITIONS FOR CANCER TREATMENT USING RECOMBINANT POLYPEPTIDES

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] [1] This application claims priority to U.S. Provisional Patent Application No. 63 / 457,918, filed on April 7, 2023, the content of which is entirely incorporated herein by reference.

[0004] BACKGROUND

[0005] [2] Esophageal cancer is one of the most lethal cancers in the world, currently ranking sixth among cancers in mortality. Esophageal cancer, including esophageal squamous cell carcinoma and esophageal adenocarcinoma, involves the abnormal proliferation of esophageal epithelial cells.

[0006] [3] Radiotherapy, surgical resection, and chemotherapy are the primary clinical treatments for esophageal cancer. Outcomes are suboptimal with only 20% of patients surviving at least 5 years following diagnosis. The survival rate of patients treated solely with chemotherapy is still low, and there is a significant need for novel, targeted therapies that demonstrate long-lasting effects.

[0007] SUMMARY OF THE DISCLOSURE

[0008] [4] Disclosed herein, in some embodiments, are methods and compositions to treat cancer in a subject, e.g., human subject using a composition comprising an epitope, e.g., T cell epitope, e.g., cancer specific CD8+ T cell epitope.

[0009] [5] In an aspects, the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, KTEVHGRLK, RVSLPKLGYK, or SLFGARPGR; the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is NLRPPTQEL; the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR; and / or the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL. [6] In an aspect, the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL; the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL; the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL; the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; the subject expresses an MHC encoded by an HLA-B*40:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; and / or the subject expresses an MHC encoded by an HLA- B*18:01 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL.

[0010] [7] In an aspect, the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK or RVFTSSLKTK; the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is RPASPRPAP; and / or the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM.

[0011] [8] In an aspect, the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL; the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, or KTEVHGRLK; the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR; the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, RPASPRPAP, NLRPPTQEL, or KPRPDVTNEL; the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, RPASPRPAP, NLRPPTQEL, or KPRPDVTNEL; the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; the subject expresses an MHC encoded by an HLA-B*40:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL or KEFAFLEHSL; the subject expresses an MHC encoded by an HLA-B*18:01 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL; and / or the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL, NLRPPTQEL or KPRPDVTNEL.

[0012] [9] In an aspect, the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope; (iii) a vector comprising (i) or (ii); (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or (v) T cells stimulated with APCs comprising (i) or (ii); wherein: the subject expresses an MHC encoded by an HLA-A*15:01 allele and the cancer-specific CD8+ T cell epitope is GQHLHLETF; the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM; the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL, NLRPPTQEL or KPRPDVTNEL; the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, KTPLHTLLK, KSYSKVLVR, MTYKIHFKK or SLYQTIRLK; the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, KPRPDVTNEL, NLRPPTQEL, RPASPRPAP, GPRPSPTRSV, SPRSPSPSL, VPQEAVRAPL, VPASPALSR, SPSARPPSL, SPTLNVSAL, or SPSSASLTL; the subject expresses an MHC encoded by an HLA-B*08:01 allele and the cancer-specific CD8+ T cell epitope is LNKVKTSL or NLKTEILRL; the subject expresses an MHC encoded by an HLA-C*07:01 allele and the cancer-specific CD8+ T cell epitope is FRGVFVHRY; the subject expresses an MHC encoded by an HLA-B*35:01 allele and the cancer-specific CD8+ T cell epitope is TSGPVTEKY; the subject expresses an MHC encoded by an HLA-A*02:05 allele and the cancer-specific CD8+ T cell epitope is VVAAHLAGA; the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL; the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; the subject expresses an MHC encoded by an HLA-B* 18:01 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL; the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR.

[0013]

[0010] In an aspect, the present disclosure provides method of treating cancer in a subject in need thereof, the method comprising administering to the subject a composition comprising (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),

[0014] (11), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii).

[0015]

[0011] In some embodiments, the subject expresses an MHC encoded by an HLA- A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, KTEVHGRLK, RVSLPKLGYK, or SLFGARPGR.

[0016]

[0012] In some embodiments, the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is NLRPPTQEL.

[0017]

[0013] In some embodiments, the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR.

[0018]

[0014] In some embodiments, the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL.

[0019]

[0015] In some embodiments, the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL.

[0020]

[0016] In some embodiments, the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL.

[0017] In some embodiments, the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is PSSASLAL, RPASPRPAP, NLRPPTQEL, or KPRPDVTNEL.

[0021]

[0018] In some embodiments, the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL.

[0022]

[0019] In some embodiments, the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL.

[0023]

[0020] In some embodiments, the subject expresses an MHC encoded by an HLA-B*40:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL. In some embodiments, the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancerspecific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL.

[0024]

[0021] In some embodiments, the subject expresses an MHC encoded by an HLA-B* 18:01 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL.

[0025]

[0022] In some embodiments, the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK or RVFTSSLKTK.

[0026]

[0023] In some embodiments, the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is RPASPRPAP.

[0027]

[0024] In some embodiments, the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM.

[0028]

[0025] In some embodiments, the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KSYSKVLVR, MTYKIHFKK, or KTEVHGRLK.

[0029]

[0026] In some embodiments, the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR.

[0030]

[0027] In some embodiments, the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, RPASPRPAP, NLRPPTQEL, VPASPALSR, SPSARPPSL, SPTLNVSAL, or KPRPDVTNEL.

[0031]

[0028] In some embodiments, the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL.

[0032]

[0029] In some embodiments, the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is KPRPDVTNEL or NLRPPTQEL.

[0033]

[0030] In some embodiments, the subject expresses an MHC encoded by an HLA-C*03:03 allele and the cancer-specific CD8+ T cell epitope is NLRPPTQEL.

[0031] In some embodiments, the subject expresses an MHC encoded by an HLA-B*15:01 allele and the cancer-specific CD8+ T cell epitope is GQHLHLETF.

[0034]

[0032] In some embodiments, the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM.

[0035]

[0033] In some embodiments, the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL.

[0036]

[0034] In some embodiments, the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, KTPLHTLLK, KSYSKVLVR, MTYKIHFKK, or SLYQTIRLK.

[0037]

[0035] In some embodiments, the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, KPRPDVTNEL, NLRPPTQEL, RPASPRPAP, GPRPSPTRSV, SPRSPSPSL, VPQEAVRAPL, VPASPALSR, SPSARPPSL, SPTLNVSAL, or SPSSASLTL.

[0038]

[0036] In some embodiments, the subject expresses an MHC encoded by an HLA-B*08:01 allele and the cancer-specific CD8+ T cell epitope is LNKVKTSL or NLKTHLRL.

[0039]

[0037] In some embodiments, the subject expresses an MHC encoded by an HLA-C*07:01 allele and the cancer-specific CD8+ T cell epitope is FRGVFVHRY.

[0040]

[0038] In some embodiments, the subject expresses an MHC encoded by an HLA-B*35:01 allele and the cancer-specific CD8+ T cell epitope is TSGPVTEKY.

[0041]

[0039] In some embodiments, the subject expresses an MHC encoded by an HLA-A*02:05 allele and the cancer-specific CD8+ T cell epitope is VVAAHLAGA.

[0042]

[0040] In some embodiments, the cancer can be a cancer selected from selected from a colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers and soft tissue sarcoma.

[0043]

[0041] In some embodiments, the polynucleotide can be a vector.

[0044]

[0042] In an aspect, the present disclosure provides a composition comprising a recombinant polypeptide or a polynucleotide encoding the recombinant polypeptide, wherein the recombinant polypeptide comprises a cancer-specific CD8+ T cell epitope which can include e.g.

[0045] GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LRPPTQEL, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, KSYSKVLVR, MTYKIHFKK, VPASPALSR, SPSARPPSL, SPTLNVSAL, and / or VVAAHLAGA or any combination thereof.

[0046]

[0043] In an aspect, the present disclosure provides a composition comprising a recombinant polypeptide or a polynucleotide encoding the recombinant polypeptide, wherein the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a cancerspecific CD8+ T cell epitope which can include GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, and / or LRPPTQEL, or any combination thereof.

[0047]

[0044] In some embodiments, the composition comprises the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g., GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL and / or HELGFKVVL, or any combination thereof.

[0048]

[0045] In some embodiments, the composition comprises the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g., LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, and / or LRPPTQEL, or any combination thereof.

[0049]

[0046] In some embodiments, the composition comprises the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g., RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, and / or RVFTSSLKTK, or any combination thereof.

[0050]

[0047] In some embodiments, the recombinant polypeptide or the recombinant polypeptide encoded by the polynucleotide comprises a single cancer-specific CD8+ T cell epitope which can include e g. IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, and / or VVAAHLAGA or any combination thereof.

[0051]

[0048] In an aspect, the present disclosure provides a composition comprising a vector encoding a recombinant polypeptide or a polynucleotide encoding the recombinant polypeptide, wherein the recombinant polypeptide comprises c a cancer-specific CD8+ T cell epitope which can include e g. GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LRPPTQEL, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, KSYSKVLVR, MTYKIHFKK, VPASPALSR, SPSARPPSL, SPTLNVSAL, and / or VVAAHLAGA or any combination thereof.

[0052]

[0049] In some embodiments, the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g. GVYDGREHTV, KLVELEHTL, LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, SLFGARPGR, SPSSASLAL, RPASPRPAP, NLRPPTQEL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, and / or LRPPTQEL, or any combination thereof.

[0053]

[0050] In some embodiments, the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL and / or HELGFKVVL, or any combination thereof.

[0054]

[0051] In some embodiments, the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, and / or LRPPTQEL, or any combination thereof.

[0055]

[0052] In some embodiments, the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, and / or RVFTSSLKTK or any combination thereof.

[0056]

[0053] In some embodiments, the vector encodes a single cancer-specific CD8+ T cell epitope which can include e.g., IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, and / or VVAAHLAGA or any combination thereof.

[0057]

[0054] In some embodiments, the cancer-specific CD8+ T cell epitope can be an esophageal cancer-specific CD8+ T cell epitope.

[0058]

[0055] In some embodiments, the vector can be a vector selected from a plasmid, a cosmid, a bacterial vector, a viral vector, an artificial chromosome, a liposome, a lipid nanoparticle, or an exosome.

[0059]

[0056] In some embodiments, the viral vector can be a viral vector, e.g., an adenovirus vector, e.g., an Ad5 vector, e.g., a replication deficient Adhu5 vector. In some embodiments, the vector is an adenoviral-associated (AAV) vector.

[0057] In some embodiments, the recombinant polypeptide is from 8 to 100 amino acids in length. In some embodiments, the recombinant polypeptide can be from 8 to 100 amino acids in length, e.g., 8 to 12 amino acids in length, e.g., 9 to 10 amino acids in length, e.g., 9 amino acids in length or 10 amino acids in length.

[0060]

[0058] In some embodiments, the cancer-specific CD8+ T cell epitope can bind to a MHC class I molecule, e.g., a with a binding affinity of 500 nM or less.

[0061]

[0059] In some embodiments, the cancer-specific CD8+ T cell epitope can bind to a MHC class I molecule, e.g., a with a predicted binding rank score of 2% or less.

[0062]

[0060] In some embodiments, the recombinant polypeptide can comprise a single cancer-specific CD8+ T cell epitope.

[0063]

[0061] In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope.

[0064]

[0062] In some embodiments, the recombinant polypeptide can comprise at least two different cancer-specific CD8+ T cell epitopes.

[0065]

[0063] In some embodiments, the recombinant polypeptide can comprise at least two different recombinant polypeptides. In some cases, each polypeptide can comprise a cancer-specific CD8+ T cell epitope.

[0066]

[0064] In some embodiments, the composition can further comprise an adjuvant.

[0067]

[0065] In some embodiments, the method can further comprise administering a second therapeutic agent, e.g., an immune checkpoint inhibitor.

[0068]

[0066] In some embodiments, the polynucleotide encoding the recombinant polypeptide can be DNA.

[0069]

[0067] In some embodiments, the polynucleotide encoding the recombinant polypeptide can be RNA, e.g., mRNA. In some embodiments, the polynucleotide encoding the recombinant polypeptide is from 18 to 45 nucleotides in length.

[0070]

[0068] In some embodiments, the composition can be for use in treating a cancer, e.g., a cancer selected from a colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers and soft tissue sarcoma, e.g., an esophageal cancer.

[0069] In some embodiments, the composition can be for use in treating a virally driven cancer. The virally driven cancer may be a cancer caused by HPV (human papilloma virus), HTLV (human T-lymphotropic virus), or EBV (Epstein Barr virus).

[0071]

[0070] In some embodiments, the composition can induce epitope-specific T cell response and / or an inflating memory CD8+ T cell response when administered to a subject.

[0072]

[0071] In some embodiments, the composition can be capable of inducing production of CD8+ T cells characterized by markers which can include e.g., CX3CR1+, KLRG-1+, CD44+, and / or CD62L-, or any combination thereof In some embodiments, the composition can be capable of inducing production of CD8+ T cells characterized by markers which can include CX3CR1+, KLRG-1+, CD44+, CD62L-, CD27-(low), and / or CD127-(low), or any combination thereof.

[0073]

[0072] In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD44+ T cells. In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD62L- T cells. In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD44+ / CD62L- T cells. In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD44+ / CD62L- / CD27- / CD127- T cells, CD8+ / CX3CRl+ / KLRG-l+ / CD44+ / CD62L- / CD27(low) / CD127- T cells, CD8+ / CX3CR1+ / KLRG-1+ / CD44+ / CD62L- / CD27- / CD127(low) T cells, or CD8+ / CX3CRl+ / KLRG-l+ / CD44+ / CD62L- / CD27(low) / CD127(low) T cells.

[0074]

[0073] In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells are further characterized by the phenotype CCR7-and / or CD45RA+ / -.

[0075]

[0074] In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that have sustained expression of Tbx21 and / or E2f2.

[0076]

[0075] In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that have low expression of Eomes.

[0077]

[0076] In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that can form about 0.01 percent to 20 percent of total circulating CD8+ T cells in the subject.

[0078]

[0077] In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that maintain a memory effector phenotype for at least 30 days.

[0079]

[0078] In some embodiments, the composition can be capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that have low expression of PD-1, Tim-3, and / or Lag-3.

[0079] In some embodiments, the composition can be capable of inducing production of an inflating memory CD8+ T cell response that can be capable of controlling tumor growth in the subject greater than 50 days after the composition is administered.

[0080]

[0080] In some embodiments, the composition can be capable of inducing production of a nucleotide sequence encoding the cancer specific CD8+ T cell epitope that encodes a polypeptide comprising the cancer specific CD8+ T cell epitope, in some cases where the polypeptide comprising the cancer specific CD8+ T cell epitope is not processed by antigen presenting cells of the subject when administered; and in some cases when a pharmaceutical composition comprising a corresponding viral vector comprising a nucleotide sequence encoding the cancer specific CD8+ T cell epitope that encodes a polypeptide comprising the cancer specific CD8+ T cell epitope that is processed by antigen presenting cells of the subject when administered, the inflating memory CD8+ T cell response is not induced in the subject.

[0081]

[0081] In some embodiments, the cancer-specific CD8+ T cell epitope can be a viral antigen, a tumor associated antigen that is overexpressed in a cancer cell, or an antigen that is mutated in a cancer cell.

[0082]

[0082] In some embodiments, the polypeptide comprising the cancer specific CD8+ T cell epitope can be not processed by antigen presenting cells.

[0083]

[0083] In some embodiments, the viral vector can include a CMV promoter and a TATA box.

[0084]

[0084] In some embodiments, the the viral vector can lack a sequence encoding the El and E3 proteins.

[0085]

[0085] In some embodiments, the composition can include at least 2, 3, 4, 5, or 6 vectors, wherein each of the at least 2, 3, 4, 5, or 6 vectors is a viral vector, and wherein each of the at least 2, 3, 4, 5, or 6 viral vectors can encode a different single cancer specific CD8+ T cell epitope.

[0086]

[0086] In some embodiments, the composition can include at least 1, 2, 3, 4, 5, or 6 vectors, wherein each of the at least 1, 2, 3, 4, 5, or 6 vectors is a viral vector, and wherein each of the at least 1, 2, 3, 4, 5, or 6 vectors can encode two different single cancer specific CD8+ T cell epitopes.

[0087]

[0087] In an aspect, the present disclosure provides a pharmaceutical composition which can include the composition described herein, and a pharmaceutically acceptable carrier, diluent, excipient, or adjuvant.

[0088]

[0088] In some embodiments, the present disclosure provides a method of treating or preventing a cancer which can include administering a therapeutically effective amount of the pharmaceutical composition described herein to a subject in need thereof.

[0089] In some embodiments, the present disclosure provides a method of inducing an inflating memory CD8+ T cell response which can include administering a therapeutically effective amount of the pharmaceutical composition described herein to a subject in need thereof, wherein the inflating memory CD8+ T cell response can include production of CD8+ / CX3CR1+ / KLRG- 1+ T cells.

[0089]

[0090] In some embodiments, the vector or composition can be administered intravenously or intramuscularly.

[0090]

[0091] In some embodiments, the composition can be administered as a single dose.

[0091]

[0092] In some embodiments, the composition can be administered as multiple doses, e.g., in two doses.

[0092]

[0093] In some embodiments, the first dose is a prime dose.

[0093]

[0094] In some embodiments, the first dose elicits a measurable immune response in a subject as compared to the immune response in the subject in the absence of administration of the first dose.

[0094]

[0095] In some embodiments, the second dose is a booster dose.

[0095]

[0096] In some embodiments, the second dose elicits a measurable immune response in a subject as compared to the immune response in the subject in the absence of administration of the second dose.

[0096]

[0097] In some embodiments, the second dose is administered 24 weeks after the first dose.

[0097]

[0098] In some embodiments, the second dose elicits an immune response that is at least 2 fold greater than the immune response elicited by the first dose.

[0098]

[0099] In some embodiments, the composition can be administered prophylactically to the subject.

[0099]

[0100] In some embodiments, the composition can be administered in combination with a second therapeutic agent, e.g., selected from an immune checkpoint inhibitor, a chemotherapeutic agent, a small molecule inhibitor, or radiotherapy.

[0100]

[0101] In some embodiments, the immune check point inhibitor can be an inhibitor of an immune checkpoint protein which can include e.g., CTLA-4, PD-1, PD-L1, PD-L2, TIM-3, LAG-3, B7-H3, B7-H4, B7-H6, A2aR, BTLA, GALS and / or IDO, or any combination thereof.

[0101]

[0102] In some embodiments, the method of treating or preventing a cancer, further comprises administering a chemotherapy course. In some embodiments, the method of treating or preventing a cancer, further comprises administering a first chemotherapy course and a second chemotherapy course. In some embodiments, the booster dose is administered 2 weeks prior to the second chemotherapy course.

[0103] In some embodiments, the method of treating or preventing a cancer, further comprises a surgery, e.g., surgical resection. In some embodiments, the booster dose is administered 1 week after post-surgical recovery.

[0102]

[0104] In an aspect, the present disclosure provides a method of producing the composition described herein comprising (i) synthesising a nucleotide sequence encoding the single cancer specific CD8+ T cell epitope, as a sense and antisense primer, (ii) cloning the nucleotide sequence encoding the single cancer specific CD8+ T cell epitope synthesized in (i) into a first plasmid, (iii) cloning a sequence comprising the nucleotide sequence encoding the single cancer specific CD8+ T cell epitope from the first plasmid of (ii) into a second vector comprising adenoviral DNA.

[0103]

[0105] In an aspect, the present disclosure provides a method of treating or preventing a cancer that can include administering a composition described herein to a subject in need thereof, wherein at least two viral vectors are present in the pharmaceutical composition at an amount that is not therapeutically effective individually, thereby treating the cancer in the subject.

[0104]

[0106] In some embodiments, the viral vector can comprise a sequence with at least 90% sequence identity to SEQ ID NO: 44 and a sequence with at least 90% sequence identity to SEQ ID NO: 45.

[0105]

[0107] In some embodiments, the viral vector can further comprise a sequence with at least 90% sequence identity to SEQ ID NO: 47 and a sequence with at least 90% sequence identity to SEQ ID NO: 48.

[0106]

[0108] In one aspect, the present disclosure provides a method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, wherein the recombinant polypeptide binds to a TCR; (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope wherein the recombinant polypeptide encoded by the polynucleotide binds to a TCR; (iii) a cell comprising a recombinant polypeptide or a polynucleotide of (i) or (ii); (iv) a recombinant polypeptide comprising an antigen binding domain wherein the antigen binding domain binds to a cancer-specific CD8+ T cell epitope; (v) a polynucleotide encoding a recombinant polypeptide comprising an antigen binding domain wherein the antigen binding domain binds to a cancer-specific CD8+ T cell epitope; or (vi) a cell comprising a recombinant polypeptide or a polynucleotide of (iii) or (iv); thereby treating the subject.

[0107]

[0109] In some embodiments, the viral vector comprises one or more of a promoter, a translation initiating sequence, a start codon, a T cell epitope codon, a stop codon, and a polyadenylation sequence, wherein (i) the promoter is selected from a CMV promoter, an RSV promoter, and an EF 1 a promoter, optionally wherein the promoter comprises a sequence as set forth in SEQ ID NO: 36; (ii) the translation initiation sequence comprises a sequence as set forth in SEQ ID NO: 37; and (iii) the polyadenylation sequence comprises a sequence as set forth in SEQ ID NO 43. [HO] In some embodiments, the vector or viral vector comprises a deletion or a functional deletion in the El gene at an El gene locus. In some embodiments, the vector or viral vector comprises a transgene insertion at the El gene locus.

[0108] [Hl] In some embodiments, the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence GVYDGREHTV, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KLVELEHTL; wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.

[0109]

[0112] In some embodiments, the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL; wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele.

[0110]

[0113] In some embodiments, the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL; wherein the subject expresses an MHC encoded by an HLA-B*35:03 allele.

[0111]

[0114] In some embodiments, the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.

[0112]

[0115] In some embodiments, the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B*40:02 allele.

[0113]

[0116] In some embodiments, the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B*44:02 allele.

[0114]

[0117] In some embodiments, the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele.

[0115]

[0118] In some embodiments, the composition comprises (i) a first adenoviral vector com-prising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence GVYDGREHTV, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KLVELEHTL.

[0116]

[0119] In some embodiments, the composition is for use in treating esophageal cancer in a subject.

[0117]

[0120] In some embodiments, the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.

[0118]

[0121] In some embodiments, the composition comprises (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the se-quence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL.

[0119]

[0122] In some embodiments, the composition is for use in treating esophageal cancer in a subject.

[0120]

[0123] In some embodiments, the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele.

[0121]

[0124] In some embodiments, the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*35:03 allele.

[0122]

[0125] In some embodiments, the composition comprises (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the se-quence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL.

[0123]

[0126] In some embodiments, the composition is for use in treating esophageal cancer in a subject.

[0124]

[0127] In some embodiments, the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.

[0128] In some embodiments, the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*40:02 allele.

[0125]

[0129] In some embodiments, the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*44:02 allele.

[0126]

[0130] In some embodiments, the composition is for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele.

[0127]

[0131] In some embodiments, the first adenoviral vector is and Ad5 adenoviral vector and / or the second adenoviral vector is and Ad5 adenoviral vector.

[0128]

[0132] In some embodiments, the first adenoviral vector comprises a deletion or a functional deletion in the El gene at an El gene locus and / or the second adenoviral vector comprises a deletion or a functional deletion in the El gene at an El gene locus.

[0129] INCORPORATION BY REFERENCE

[0130]

[0133] All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference.

[0131] BRIEF DESCRIPTION OF THE DRAWINGS

[0132]

[0134] The features of the disclosure are set forth with particularity in the appended claims. A better understanding of the features and the disclosure 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:

[0133]

[0135] FIG. 1 shows a schematic diagram of the proposed clinical trial protocol.

[0134]

[0136] FIG. 2 shows a schematic diagram of a proposed clinical trial study design.

[0135]

[0137] FIG. 3 shows events at timepoints of a proposed clinical trial design.

[0136] DETAILED DESCRIPTION OF THE DISCLOSURE

[0137]

[0138] Immunotherapeutic approaches have been broadly used to treat cancer by modulating T cells to recognize cancerous cells, causing leukocytes to attack the cancer. Epitope-based cancer vaccines are one strategy that has been used to activate a T cell response to specific tumor associated antigens (TAAs). TAAs are highly expressed on tumor cells and expressed to a lesser extent on normal tissue. Initially, peptide-based single epitope vaccines were used, however these provided poor clinical responses as they did not adequately active the innate immune system.

[0139] The present disclosure provides recombinant polypeptides comprising at least one T cell epitope, e.g., a CD8+ T cell epitope, e.g., a cancer-specific CD8+ T cell epitope, polynucleotides encoding the T cell epitopes, e.g., a CD8+ T cell epitopes, vectors, cells, compositions, pharmaceutical compositions, formulation, and methods of using such.

[0138]

[0140] The practice of the present disclosure will employ, unless otherwise indicated, conventional techniques of immunology, molecular biology, chemistry, biochemistry and recombinant DNA technology, which are within the skill of the art. Such techniques are explained fully in the literature, see, e.g., Green and Sambrook et al., Molecular Cloning: A Laboratory Manual, 4th ed., Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. (2012).

[0139] Definitions

[0140]

[0141] Unless defined otherwise, all terms of art, notations and other technical and scientific terms or terminology used herein are intended to have the same meaning as is commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. In some cases, terms with commonly understood meanings are defined herein for clarity and / or for ready reference, and the inclusion of such definitions herein should not necessarily be construed to represent a substantial difference over what is generally understood in the art. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0141]

[0142] As used in the specification and claims, the singular forms “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a sample” includes a plurality of samples, including mixtures thereof.

[0142]

[0143] Furthermore, to the extent that the terms “including”, “includes”, “having”, “has”, “with”, or variants thereof as used herein mean “comprising”. Unless otherwise specified, the words “comprising”, “comprise”, “comprises”, “having”, “have”, “has”, “including”, “includes”, “include”, “containing”, “contains” and “contain” are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0143]

[0144] The term “and / or” as used in a phrase such as “X and / or Y” herein is intended to include both X and Y; X or Y; X (alone); and Y (alone).

[0144]

[0145] Reference to “some embodiments”, “an embodiment”, “one embodiment”, or “other embodiments” means that a particular feature or characteristic described in connection with the embodiments is included in at least one or more embodiments, but not necessarily all embodiments, of the present disclosure.

[0146] The term “about” or “approximately” as disclosed herein refers to in relation to a numerical value means a range of values that fall within 15% greater than or 15% less than the value.

[0145]

[0147] Ranges: throughout this disclosure, various aspects of the present disclosure can be presented in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 2.7, 3, 4, 5, 5.3, and 6. As another example, a range such as 95-99% identity, includes something with 95%, 96%, 97%, 98% or 99% identity, and includes subranges such as 96-99%, 96-98%, 96-97%, 97-99%, 97-98% and 98-99% identity. This applies regardless of the breadth of the range.

[0146]

[0148] As used herein, the terms “determining,” “measuring,” “evaluating,” “assessing,” “assaying,” and “analyzing” are often used interchangeably herein to refer to forms of measurement. The terms include determining if an element is present or not (for example, detection). These terms can include quantitative, qualitative or quantitative and qualitative determinations. Assessing can be relative or absolute. “Detecting the presence of can include determining the amount of something present in addition to determining whether it is present or absent depending on the context.

[0147]

[0149] As used herein, the term “cancer” as used herein refers to diseases with abnormal cell growth, as used herein the term refers to both a primary tumor and metastasis of the primary tumor. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body. Examples of various cancers include but are not limited to colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, breast cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers and soft tissue sarcoma. The cancer described herein can be a stage I cancer, a stage II cancer, a stage III cancer, or a stage IV cancer. As used herein, the term “tumor” refers to the physiological condition in mammals characterized by deregulated cell growth.

[0150] As used herein the term “individual,” “patient,” or “subject” refers to individuals diagnosed with, suspected of being afflicted with, or at-risk of developing at least one disease for which the described compositions and methods are useful for treating. In certain embodiments, the individual is a human.

[0148]

[0151] In some embodiments, the individual is a mammal. In some embodiments, the mammal is a non-human primate (e.g., rhesus or other types of macaques), mouse, rat, rabbit, dog, cat, horse, cow, sheep, pig, goat, llama, alpaca, or yak. In certain embodiments, the individual is a human.

[0149]

[0152] The term “linker” as used herein refers to a molecule linking two other molecules or moi eties. The linker can be an amino acid sequence in the case of a linker joining two fusion proteins. The linker can also be a nucleotide sequence in the case of joining two nucleotide sequences together. In some cases, a linker may have various lengths, depending on the application of a linker or the sequences or molecules being linked by a linker.

[0150]

[0153] As used herein, the terms “treatment” or “treating” are used in reference to a pharmaceutical or other intervention regimen used for obtaining beneficial or desired results in the recipient. Beneficial or desired results include but are not limited to a therapeutic benefit and / or a prophylactic benefit. A therapeutic benefit may refer to eradication or amelioration of symptoms or of an underlying disorder being treated. Also, a therapeutic benefit can be achieved with the eradication or amelioration of one or more of the physiological symptoms associated with the underlying disorder such that an improvement is observed in the subject, notwithstanding that the subject may still be afflicted with the underlying disorder. A prophylactic effect includes delaying, preventing, or eliminating the appearance of a disease or condition, delaying or eliminating the onset of symptoms of a disease or condition, slowing, halting, or reversing the progression of a disease or condition, or any combination thereof. For prophylactic benefit, a subject at risk of developing a particular disease, or to a subject reporting one or more of the physiological symptoms of a disease may undergo treatment, even though a diagnosis of this disease may not have been made. Skilled artisans will recognize that given a population of potential individuals for treatment not all will respond or respond equally to the treatment. Such individuals are considered treated if administered the compositions including the pharmaceutical compositions described herein.

[0151]

[0154] As used herein, the term “effective amount”, “therapeutically effective amount” or “pharmaceutically effective amount” refers to an amount that is sufficient to effect treatment, as defined below, when administered to a subject (e.g., a mammal, such as a human) in need of such treatment. The therapeutically or pharmaceutically effective amount will vary depending upon the subject and disease condition being treated, the weight and age of the subject, the severity of the disease condition, the manner of administration and the like, which can readily be determined by one of ordinary skill in the art. For example, a “therapeutically effective amount” or a “pharmaceutically effective amount” of AAV2-derived capsid as described herein is an amount sufficient to generate an immune response in a subject (e.g., a human). In some embodiments, the immune response is sufficient to raise AAV capsid neutralizing antibodies against the relevant capsid(s) in the subject.

[0152]

[0155] The term “sequence identity” as used herein refers to the subunit sequence identity between two polymeric molecules, for example, between two polynucleotide or polypeptide sequences. An analysis of sequence identity begins by aligning two sequences. Identical sequences (100% sequence identity) have the same nucleotide or amino acid at each position of the alignment. “Percent sequence identity” is determined by comparing the number of positions that are identical to the total number of subunits in the sequence alignment. Percent sequence identity can be determined over a fraction of the sequences or over the whole of the sequences. Percent sequence identity can be determined using a sequence comparison algorithm. Test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then aligns the sequences and calculates the percent sequence identity based on the designated program parameters.

[0153]

[0156] Sequence identity is typically measured using sequence analysis software. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat’l. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection (see generally Ausubel el al, Current Protocols in Molecular Biology). Such software matches identical or similar sequences by assigning degrees of homology to various substitutions, deletions, and / or other modifications. In an exemplary approach to determining the degree of identity, a BLAST program may be used, with a probability score between e-3 and e- 100 indicating a closely related sequence. One example of algorithm that is suitable for determining percent sequence identity and sequence similarity is the BLAST algorithm, which is described in Altschul et al, J. Mol. Biol. 215:403 (1990). Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (publicly accessible through the National Institutes of Health NCBI internet server). Typically, default program parameters can be used to perform the sequence comparison, although customized parameters can also be used. For amino acid sequences, the BLASTP program uses as defaults a wordlength (W) of 3, an expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Set. USA 89: 10915 (1989)). In some embodiments, the sequence identities are determined by Needleman-Wunsch alignment of two sequences with Gap Costs set to Existence: 11 Extension: 1 where percent identity is calculated by dividing the number of identities by the length of the alignment. Conservative substitutions typically include substitutions within the following groups: glycine, alanine; valine, isoleucine, leucine; aspartic acid, glutamic acid, asparagine, glutamine; serine, threonine; lysine, arginine; and phenylalanine, tyrosine.

[0154]

[0157] As used herein, the term “antigen presenting cell” or “APC” refers to an immune system cell such as an accessory cell (e.g., a B-cell, a dendritic cell, and the like) that displays a foreign antigen complexed with major histocompatibility complexes (MHC’s) on its surface. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T cells.

[0155]

[0158] The term “encoding” refers to the inherent property of specific sequences of nucleotides in a polynucleotide, such as a gene, a cDNA, or an mRNA, to serve as templates for synthesis of other polymers and macromolecules in biological processes having either a defined sequence of nucleotides (e.g., rRNA, tRNA, and mRNA) or a defined sequence of amino acids and the biological properties resulting therefrom. Thus, a gene, cDNA, or RNA, encodes a protein if transcription and translation of mRNA corresponding to that gene produces the protein in a cell or other biological system. Both the coding strand, the nucleotide sequence of which is identical to the mRNA sequence and is usually provided in sequence listings, and the non-coding strand, used as the template for transcription of a gene or cDNA, can be referred to as encoding the protein or other product of that gene or cDNA.

[0156]

[0159] Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain one or more introns.

[0157]

[0160] The term “T cell” and its grammatical equivalents as used herein can refer to a T cell from any origin. For example, a T cell can be a primary T cell, e.g., an autologous T cell, an allogenic T cell, a cell line, etc. The T cell can also be human or non-human in origin.

[0161] The term “CD8” as used herein refers to the Cluster of Differentiation 8 protein, a transmembrane glycoprotein that serves as a co-receptor for the T-cell receptor (TCR).

[0158]

[0162] As used herein, the term “effector T cell” includes T helper (e.g., CD4+) cells and cytotoxic (e.g., CD8+) T cells. CD4+ effector T cells contribute to the development of several immunologic processes, including maturation of B cells into plasma cells and memory B cells, and activation of cytotoxic T cells and macrophages. CD8+ effector T cells destroy virus- infected cells and tumor cells.

[0159]

[0163] As used herein, the term “nucleic acid” or “polynucleotide” refers to deoxyribonucleic acids (DNA) or ribonucleic acids (RNA) and polymers thereof in either single- or doublestranded form. Unless specifically limited, the term encompasses nucleic acids containing known analogues of natural nucleotides that have similar binding properties as the reference nucleic acid and are metabolized in a manner similar to naturally occurring nucleotides. Unless otherwise indicated, a particular nucleic acid sequence also implicitly encompasses conservatively modified variants thereof (e.g., degenerate codon substitutions), alleles, orthologs, SNPs, and complementary sequences as well as the sequence explicitly indicated. Specifically, degenerate codon substitutions may be achieved by generating sequences in which the third position of one or more selected (or all) codons is substituted with mixed-base and / or deoxyinosine residues (Batzer et al., Nucleic Acid Res. 19:5081 (1991); Ohtsuka et al., J. Biol. Chem. 260:2605-2608 (1985); and Rossolini et al., Mol. Cell. Probes 8:91-98 (1994)).

[0160]

[0164] As used herein, the terms “peptide,” “polypeptide,” and “protein” are used interchangeably, and refer to a compound comprised of amino acid residues covalently linked by peptide bonds. A protein or peptide must contain at least two amino acids, and no limitation is placed on the maximum number of amino acids that can comprise a protein’s or peptide’s sequence. Polypeptides include any peptide or protein comprising two or more amino acids joined to each other by peptide bonds. As used herein, the term refers to both short chains, which also commonly are referred to in the art as peptides, oligopeptides and oligomers, for example, and to longer chains, which generally are referred to in the art as proteins, of which there are many types. “Polypeptides” include, for example, biologically active fragments, substantially homologous polypeptides, oligopeptides, homodimers, heterodimers, variants of polypeptides, modified polypeptides, derivatives, analogs, fusion proteins, among others. A polypeptide includes a natural peptide, a recombinant peptide, or a combination thereof.

[0161]

[0165] The term “promoter” refers to a DNA sequence recognized by the transcription machinery of the cell, or introduced synthetic machinery, required to initiate the specific transcription of a polynucleotide sequence.

[0166] The term “promoter / regulatory sequence” refers to a nucleic acid sequence which is required for expression of a gene product operably linked to the promoter / regulatory sequence. In some instances, this sequence may be the core promoter sequence and in other instances, this sequence may also include an enhancer sequence and other regulatory elements which are required for expression of the gene product. The promoter / regulatory sequence may, for example, be one which expresses the gene product in a tissue specific manner.

[0162]

[0167] As used herein, the term “vector” refers to a nucleic acid sequence capable of transporting into a cell another nucleic acid to which the vector sequence has been linked. Numerous vectors are known in the art including, but not limited to, linear polynucleotides, polynucleotides associated with ionic or amphiphilic compounds, plasmids, and viruses. Examples of viral vectors include, but are not limited to, adenoviral vectors, adeno-associated virus vectors (AAVs), retroviral vectors, lentiviral vectors, and the like. A vector of the present disclosure can be adenoviral and comprises the nucleotide sequence encoding a single cancer specific CD8+ T cell epitope containing a gene construct in a form suitable for expression by a cell (e.g., linked to a transcriptional control element).

[0163]

[0168] As used herein, the term “epitope” refers to a part of an antigen that is recognized by the immune system which may be a short protein sequence. A “cancer specific CD8+ T cell epitope” refers to an epitope that may be presented by an antigen presenting cell bound to an MHC molecule which are then recognized by the T-cell receptor (TCR). CD8+ T cells express the CD8 coreceptor, which binds to MHC I, and recognize peptides presented by MHC I molecules.

[0164]

[0169] As used herein, the term “HLA binding affinity” or “MHC binding affinity” means affinity of binding between a specific antigen and a specific MHC allele.

[0165]

[0170] As used herein, the term “HLAbinding rank score” or “MHC binding rank score” means the predicted rank score. The predicted rank score is a percentage rank position of a query sequence (antigen) in relation to a distribution of prediction scores for the MHC in question, estimated from a set of random natural peptides. A rank score below the value of 2% indicates binding between a specific antigen and a specific MHC allele. Provided herein are methods to treat cancer in a human subject, e.g., by administering recombinant polypeptides (or polynucleotides encoding the recombinant polypeptide) comprising a T cell epitope that is capable of binding to one or more MHC molecules, presented by the one or more MHC molecules, being immunogenic and / or capable of activating T cells to become cytotoxic and compositions thereof. In some embodiments, an epitope described herein (e.g., a single cancerspecific CD8+ T cell epitope) may bind to a MHC (e.g., a MHC class I) molecule with a rank score (e.g., a binding rank score) of at least about 0.5%, at least about 1%, at least about 1.5%, at least about 2%, at least about 2.5%, at least about 3%, at least about 3.5%, at least about 4%, at least about 5%, or greater than about 5%. In some embodiments, an epitope described herein (e.g., a single cancer-specific CD8+ T cell epitope) may bind to a MHC (e.g., a MHC class I) molecule with a rank score (e.g., a binding rank score) of at most about 5%, at most about 4%, at most about 3.5%, at most about 3%, at most about 2.5%, at most about 2%, at most about 1.5%, at most about 1%, at most about 0.5%, or less than about 0.5%.

[0166] Recombinant Polypeptides

[0167]

[0171] In one aspect, the present disclosure provides a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or a CD4+ epitope, e.g., a single cancer-specific CD8+ epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or a CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is an immunogenic epitope, e.g., it elicits an immune response. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or a CD4+ epitope, e.g., the single cancer-specific CD8+ epitope binds to a major histocompatibility complex (MHC complex), e.g., an MHC associated with a cell, e.g., a cancer cell. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or a CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is capable of binding and presenting on an MHC molecule, an MHC molecule associated with a cell, e.g., a cancer cell.

[0168]

[0172] MHC molecules are highly polymorphic proteins that regulate T cell responses (Schwartz, B. D., The human major histocompatibility complex HLA in basic & clinical immunology Stites et al, eds., Lange Medical Publication: Los Altos, pp. 52-64, 4th ed.). The MHC system is responsible for presenting epitopes to responding T cells. The species-specific MHC homologues that display cytotoxic T-cell lymphocyte (CD8+) epitopes or helper T-cell lymphocyte (CD4+) epitopes in humans are termed human leukocyte antigen (“HLA”). HLA class I and class II molecules can be divided into several families or “supertypes” based upon their ability to bind similar repertoires of peptides. HLA class I (HLA-A, -B, and -C) and peptide complexes are recognized by CD8+ T cells which may then target the presenting cell for destruction. HLA class II (HLA-DP, -DQ, and -DR) and peptide complexes are recognized by CD4+ T cell which may then initiate an immune response towards the presenting cell. In order to trigger an immune response, the tumor-specific peptide must be bound to an MHC molecule. This binding is dependent on the allele of the MHC molecule and specific polymorphisms of the amino acid sequence of the epitope. In some cases, the recombinant polypeptide can comprise a cancer-specific CD8+ T cell epitope that can bind to a MHC class I molecule. In some cases, the recombinant polypeptide can comprise a cancer-specific CD4+ T cell epitope that can bind to a MHC class II molecule.

[0169]

[0173] In some embodiments, the epitope e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ epitope binds to an MHC encoded by an HLA, e.g., an HLA-A allele, e.g., an HLA-B allele, e.g., an HLA-C allele. In some embodiments the HLA-A allele is an HLA-A* 11 allele (e.g., an HLA-A* 11 :01 allele), an HLA-A*02 allele (e.g., an HLA-A*02:01 allele, e.g., an HLA-A*02:05 allele), an HLA-A*03 allele (e.g., an HLA-A*03:01 allele,), or an HLA-A*31 allele (e.g., an HLA-A*31 :01 allele). In some embodiments the HLA-B allele is an HLA-B*07 allele (e.g., an HLA-B*07:02 allele), an HLA-B*08 allele (e.g., an HLA-B*08:01 allele), an HLA-B*15 allele (e.g., an HLA-B*15:01 allele), an HLA-B*18 allele (e.g., an HLA-B*18:01 allele), an HLA-B*35 allele (e.g., an HLA-B*35:01 allele, an HLA-B*35:03 allele), an HLA- B*40 allele (e.g., an HLA-B*40:01 allele, e.g., an HLA-B*40:02 allele), or an HLA-B*44 allele (e.g., an HLA-B*44:01 allele, e.g., an HLA-B*44:02 allele). In some embodiments the HLA-C allele is an HLA-C*03 allele, (e.g. an HLA-C*03:04 allele), or an HLA-C*07 allele, (e.g., an HLA-C*07:01 allele, e.g., an HLA-C*07:02 allele). In some embodiments, the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope can bind to multiple MHCs encoded by different HLAs, e.g., a single T cell epitope. In some embodiments, a single T cell epitope, e.g., a single cancer-specific CD8+ epitope disclosed herein can bind to an MHC encoded by an HLA selected from HLA-B*40:01, HLA-B*44:01, HLA-B*44:02, or HLA-B*18:01. In some embodiments, the epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope disclosed herein binds to an MHC encoded by an HLAalleles it is predicted to bind to.

[0170]

[0174] Predicted binding affinities and ranks for MHC molecules can help prioritize peptides for experimental testing. Multiple methods are known in the art to predict the binding of peptides to MHC class I and MHC class II complexes and can include, but are not limited to, NetMHC, NetMHCpan, NetMHCllpan, stabilized matrix method (SMM), and / or average relative binding matrix (ARB). In some instances, the predicted binding rank score can be between 4% and less than 0.1% including 0%, between 3.5% and 02%, between 3% and 0.5%, between 2.5% and 1%, between 2.25% and 1.5%, between 2% and 1%, between 2% and 0.5%, between 0.5% and 0.4%, between 0.4% and 0.3%, between 0.3% and 0.2%, between 0.2% and 0.1%, or less than 0.1% including 0%.

[0175] In some instances, the binding affinity can be about 500 nM or less than 500 nM. For example, the binding affinity can be about between 500 nM and 400 nM, about between 400 nM and 300 nM, about between 300 nM and 200 nM, about between 200 nM and 100 nM, or about less than 100 nM including 0 nM. In some embodiments, an epitope described herein (e.g., a single cancer-specific CD8+ T cell epitope) may bind to a MHC (e.g., a MHC class I) molecule with a binding affinity of at most about 750 nM, at most about 500 nM, at most about 400 nM, at most about 300 nM, at most about 200 nM, at most about 100 nM, at most about 50 nM, or less than about 50 nM.

[0171]

[0176] In some embodiments, binding of the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope to the MHC complex initiates a subsequent immune response, e.g., an inflating memory T cell response, e.g., an inflating memory CD8+ and / or CD4+ T cell response, e.g., an inflating memory CD8+ T cell response. In some embodiments, the inflating memory T cell response, e.g., the inflating memory CD8+ and / or CD4+ T cell response, e.g., the inflating memory CD8+ T cell response targets cancer cells. In some embodiments, the recombinant polypeptide comprising the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope binds an HLA type encoding an MHC of a patient’s cancer cells. In some embodiments, the recombinant polypeptide comprising the single epitope, e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ and / or epitope, e.g., the single cancer-specific CD8+ epitope does not bind to an HLA type encoding an MHC of a patient’s non-cancer cells. In some embodiments, the recombinant polypeptide comprising the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope does not cause T cell exhaustion while binding to the HLA type encoding the MHC of the patient’s cancer cells.

[0172]

[0177] There are multiple methods known in the art to identify epitopes which bind the MHC and therefore produce an immune response, e.g., peptide-MHC binding prediction models of which there are multiple programs publicly available.

[0173]

[0178] In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence selected from Table 1. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., a single cancerspecific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.

[0174]

[0179] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancerspecific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.

[0175]

[0180] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancerspecific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.

[0176]

[0181] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., the single cancerspecific CD4+ and / or CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.

[0177]

[0182] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18. In some embodiments, the recombinant polypeptide comprises a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence selected from any of the SEQ ID NOs: 19-35, an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 19-35, or an amino acid sequence with 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 19-35.

[0178] Table 1: Exemplary Epitope Sequences

[0179]

[0183] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-35.

[0180]

[0184] In some embodiments, the single cancer-specific T cell epitope (e.g., the single cancer specific CD8+ T cell epitope) may comprise an amino acid sequence having at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 98.5%, at least about 99%, at least about 99.5%, at least about 99.9%, or greater than about 99.9% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs: 1-35. In some embodiments, the single cancer-specific T cell epitope (e.g., the single cancer specific CD8+ T cell epitope) may comprise an amino acid sequence having at most about 99.9%, at most about 99.5%, at most about 99%, at most about 98.5%, at most about 98%, at most about 97%, at most about 96%, at most about 95%, at most about 94%, at most about 93%, at most about 92%, at most about 91%, at most about 90%, or less than about 90% sequence identity to an amino acid sequence as set forth in any one of SEQ ID NOs: 1-35.

[0181]

[0185] In some embodiments, the single cancer-specific T cell epitope (e.g., the single cancer specific CD8+ T cell epitope) may comprise an amino acid sequence having from about 90% to about 99.9%. In some embodiments, the single cancer-specific T cell epitope (e.g., the single cancer specific CD8+ T cell epitope) may comprise an amino acid sequence having from about 90% to about 91%, about 90% to about 92%, about 90% to about 93%, about 90% to about 94%, about 90% to about 95%, about 90% to about 96%, about 90% to about 97%, about 90% to about 98%, about 90% to about 99%, about 90% to about 99.5%, about 90% to about 99.9%, about 91% to about 92%, about 91% to about 93%, about 91% to about 94%, about 91% to about 95%, about 91% to about 96%, about 91% to about 97%, about 91% to about 98%, about 91% to about 99%, about 91% to about 99.5%, about 91% to about 99.9%, about 92% to about 93%, about 92% to about 94%, about 92% to about 95%, about 92% to about 96%, about 92% to about 97%, about 92% to about 98%, about 92% to about 99%, about 92% to about 99.5%, about 92% to about 99.9%, about 93% to about 94%, about 93% to about 95%, about 93% to about 96%, about 93% to about 97%, about 93% to about 98%, about 93% to about 99%, about 93% to about 99.5%, about 93% to about 99.9%, about 94% to about 95%, about 94% to about 96%, about 94% to about 97%, about 94% to about 98%, about 94% to about 99%, about 94% to about 99.5%, about 94% to about 99.9%, about 95% to about 96%, about 95% to about 97%, about 95% to about 98%, about 95% to about 99%, about 95% to about 99.5%, about 95% to about 99.9%, about 96% to about 97%, about 96% to about 98%, about 96% to about 99%, about 96% to about 99.5%, about 96% to about 99.9%, about 97% to about 98%, about 97% to about 99%, about 97% to about 99.5%, about 97% to about 99.9%, about 98% to about 99%, about 98% to about 99.5%, about 98% to about 99.9%, about 99% to about 99.5%, about 99% to about 99.9%, or about 99.5% to about 99.9%.

[0182]

[0186] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-13.

[0183]

[0187] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 1-6.

[0184]

[0188] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 7-12.

[0185]

[0189] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ and / or CD8+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence 1, 2, or at most 3 amino acid mutations compared to an amino acid sequence as set forth in any of the SEQ ID NOs: 13-18.

[0186]

[0190] In some embodiments overexpressed antigens can have lower expression levels in normal tissues and high expression levels in tumors.

[0191] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 1. In some embodiments the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 1. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 2. In some embodiments the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 2. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 3. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 3. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancerspecific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 4. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 4. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 5. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 5. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 6. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 6.

[0192] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 7. In some embodiments the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 7. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 8. In some embodiments the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 8. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 9. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 9. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancerspecific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 10. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 10. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 11. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 11. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 12. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 12.

[0193] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 13. In some embodiments the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 13. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 14. In some embodiments the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 14. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancerspecific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 15. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 15. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancerspecific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 16. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 16. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 17. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 17. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence as set forth in SEQ ID NO: 18. In some embodiments, the epitope, e.g., the T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope comprises an amino acid sequence with 90-99% identity to the amino acid sequence of the epitope as set forth in SEQ ID NO: 18.

[0194] In some embodiments, the recombinant polypeptide is from 8 to 100 amino acids in length. In some embodiments, the recombinant polypeptide is from 5 to 15 amino acids (e.g., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15) in length. In some embodiments, the recombinant polypeptide is from 8 to 12 amino acids in length. In some embodiments, the recombinant polypeptide is from 9 to 10 amino acids in length. In some embodiments, the recombinant polypeptide is 8 amino acids in length. In some embodiments, the recombinant polypeptide is 9 amino acids in length. In some embodiments, the recombinant polypeptide is 10 amino acids in length. In some embodiments, the recombinant polypeptide is 11 amino acids in length. In some embodiments, the recombinant polypeptide is 12 amino acids in length.

[0187]

[0195] In some embodiments, the recombinant polypeptide comprises more than one, e.g., 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, or 30 epitopes, e.g., T cell epitopes, e.g., cancer-specific CD8+ and / or CD4+ epitopes, e.g., cancer-specific CD8+ epitopes. In some embodiments, the recombinant polypeptide comprises at least two epitopes, e.g., at least two T cell epitopes, e.g., at least two cancer-specific CD8+ and / or CD4+ epitopes, e.g., at least two cancer-specific CD8+ epitopes. In some embodiments, the epitopes are identical. In some embodiments, the epitopes are different. In a non-limiting example, in some embodiments, a recombinant polypeptide disclosed herein may comprise three epitopes e.g., T cell epitopes, e.g., cancer-specific CD8+ and / or CD4+ epitopes, e.g., cancer-specific CD8+ epitopes of which two are identical and one different. In some embodiments, the first epitope e.g., the first T cell epitope, e.g., the first cancer-specific CD8+ and / or CD4+ epitope, e.g., the first cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the second epitope e.g., the second T cell epitope, e.g., the second cancer-specific CD8+ and / or CD4+ epitope, e.g., the second cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the third epitope e.g., the third T cell epitope, e.g., the third cancer-specific CD8+ and / or CD4+ epitope, e.g., the third cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the fourth epitope e.g., the fourth T cell epitope, e.g., the fourth cancer- specific CD8+ and / or CD4+ epitope, e.g., the fourth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the fifth epitope e.g., the fifth T cell epitope, e.g., the fifth cancer-specific CD8+ and / or CD4+ epitope, e.g., the fifth cancerspecific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the sixth epitope e.g., the sixth T cell epitope, e.g., the sixth cancerspecific CD8+ and / or CD4+ epitope, e.g., the sixth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the seventh epitope e.g., the seventh T cell epitope, e.g., the seventh cancer-specific CD8+ and / or CD4+ epitope, e.g., the seventh cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the eighth epitope e.g., the eighth T cell epitope, e.g., the eighth cancer-specific CD8+ and / or CD4+ epitope, e.g., the eighth cancerspecific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the ninth epitope e.g., the ninth T cell epitope, e.g., the ninth cancerspecific CD8+ and / or CD4+ epitope, e.g., the ninth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35. In some embodiments, the tenth epitope e.g., the tenth T cell epitope, e.g., the tenth cancer-specific CD8+ and / or CD4+ epitope, e.g., the tenth cancer-specific CD8+ epitope comprises an amino acid sequence set forth in any of SEQ ID NOs: 1-35.

[0188]

[0196] In some embodiments, the epitope, e.g., the T cell epitope, e.g., the cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope is derived from a tumor associated antigen (TAA). A TAA is an antigenic product produced by a cancer and it provides a biomarker for targeted identification of a tumor. TAAs can be broadly categorized into aberrantly expressed self-antigens, mutated self-antigens and tumor specific antigens. As such, the TAA may be upregulated or over-expressed in the cancer cell. The TAA may be mutated within the cancer cell. The TAA may be specific for the cancer cell and only expressed within the cancer cell, this may also be referred to as a tumor specific antigen. The TAA may be overexpressed antigens that have lower expression levels in normal tissues and high expression levels in tumors.

[0189]

[0197] In some embodiments the TAA is associated with aggressive tumor behavior and / or show cancer-restricted expression. In some embodiments, the TAA enhances a CD8+ T cell immune response. In some embodiments, the tumor-associated antigen (TAA) is a tumor specific antigen. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ epitope is a cancer testis antigen, e.g., a cancer testis antigen that is NY-ESO-1 or a member of the MAGE-A family. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope is an endogenous retroviral protein.

[0190]

[0198] In some embodiments the TAA is associated with aggressive tumor behavior and / or show cancer-restricted expression. In some embodiments, the TAA enhances a CD4+ T cell immune response. In some embodiments, the tumor-associated antigen (TAA) is a tumor specific antigen. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancerspecific CD4+ epitope is a cancer testis antigen, e.g., a cancer testis antigen that is NY-ESO-1 or a member of the MAGE-A family. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ epitope is an endogenous retroviral protein.

[0199] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is mutated in a cancer cell. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is overexpressed in a cancer cell. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is or comprises a non-coding tumor specific epitope. As used herein the term “non-coding tumor specific epitope” refers to a peptide found on a cancer cell, wherein the peptide is derived from a nucleotide sequence that is epigenetically suppressed in healthy cells. These peptide sequences are aberrantly expressed within tumor cells.

[0191]

[0200] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is not a cryptic epitope. As used herein a “cryptic epitope” refers to an epitope which is not immunogenic in immunocompetent individuals. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a cryptic epitope.

[0192]

[0201] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope can be a viral epitope optionally associated with a virally driven cancer. The virally driven cancer may be a cancer caused by HPV (human papilloma virus), HTLV (human T-lymphotropic virus), or EBV (Epstein Barr virus).

[0193]

[0202] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ epitope is or is derived from a tumor associated antigen selected from the group comprising: TRP-1, CEA, TAG-72, 9D7, Ep-CAM, EphA3, telomerase, mesothelin, SAP- 1 Mel an- ATM ART- 1, tyrosinase, CLPP, cyclin-Al, cyclin-Bl MAGE- Al, MAGE-CI, MAGE- 02, SSX2, XAGElb / GAGED2a, CD45, glypican-3, IGF2B3, kallikrein-4, KIF20A, lengsin, meloe, MUC5AC, survivin, PRAME, SSX-2, NY-ESO-1 / LAGE1, gp70, MC1R, TRP-1 / -2, 0- catenin, BRCA1 / 2, or CDK4.

[0194]

[0203] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD4+ epitope is or is derived from a tumor associated antigen selected from the group comprising: EBNA2, TARP, EBV LMP1, STEAP, WT1, HTLV-1 env, HER2 / neu, MAGE- A3, BRAF-V600E, NY-ESO-1, or gplOO.

[0195]

[0204] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is an epitope associated with colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers or soft tissue sarcoma. In some embodiments, the cancer is a primary cancer. In some embodiments, the cancer is a relapsed and / or a refractory cancer.

[0196]

[0205] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is an esophageal cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a colorectal cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a prostate cancerspecific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is a liver cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a renal cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a breast cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a bladder cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a pancreatic cancerspecific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is a lung cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a brain cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a hepatocellular cancer-specific CD8+ T cell epitope. In some embodiments the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a gastric cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a cervical cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is an ovarian cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a thyroid cancer-specific CD8+ T cell epitope. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for melanoma. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for lymphoma. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for leukemia. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope specific for carcinoma. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for head and neck cancer. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancerspecific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for skin cancer. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is a CD8+ T cell epitope specific for soft tissue sarcoma. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is a CD8+ T cell epitope specific for nasopharyngeal cancer.

[0197]

[0206] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope may be a private epitope. As used herein the term “private epitope” refers to an epitope which is found exclusively on a single antigen in a cancer of a single person. In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope may be a public epitope. As used herein the term “public epitope” refers to an epitope that is found on a cancer of two or more people.

[0198]

[0207] In some embodiments, the recombinant polypeptide comprising the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is capable of inducing an epitope-specific T cell response. In some embodiments, the recombinant polypeptide comprising the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope is capable of inducing an inflating memory CD8+ T cell response. In some embodiments, the recombinant polypeptide comprising the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope, is not processed by a proteasome or immunoproteasome in antigen presenting cells (APCs).

[0199]

[0208] In some embodiments, the single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancer-specific CD8+ epitope may be a neoepitope. As used herein the term “neoepitope” refers to epitopes which have arisen through mutations within the tumor cells, in particular somatic or passenger mutations may lead to the production of a neoepitope. In some embodiments, single epitope, e.g., the single T cell epitope, e.g., the single cancer-specific CD8+ and / or CD4+ epitope, e.g., the single cancerspecific CD8+ epitope is not a neoepitope. In some embodiments, the recombinant polypeptide can be a glycoconjugate protein. In some embodiments, the recombinant polypeptide can be a ubiquitinated protein. In some embodiments, the recombinant polypeptide can be a phosphorylated protein. In some embodiments, the recombinant polypeptide can be an acetylated protein. In some embodiments, the recombinant polypeptide can be a methylated protein. In some embodiments, the recombinant polypeptide comprises a signal peptide. “Signal peptide” as used herein refers to an amino acid sequence that can be linked at the amino terminus of recombinant polypeptide disclosed herein. Signal peptides typically direct localization of a protein.

[0200] Polynucleotides

[0201]

[0209] In one aspect, the disclosure provides a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope described herein. In some embodiments, a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35. In some embodiments, a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-13. In some embodiments, a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-6. In some embodiments, a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 7-12. In some embodiments, a polynucleotide encodes a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 13-18.

[0202]

[0210] Polynucleotides includes, for example, genomic DNA, cDNA, RNA, e.g., mRNA, and DNA-RNA hybrid molecules. Polynucleotides can be naturally occurring, recombinant, or synthetic. In addition, polynucleotides can be single-stranded, double-stranded or triple-stranded. In certain embodiments, polynucleotides can be modified. In the case of a double-stranded polymer, “nucleic acid” can refer to either or both strands of the molecule. In some embodiments, the polynucleotide is provided as DNA. In some embodiments, the polynucleotide is provided as RNA, e.g., an mRNA. In some embodiments, a polynucleotide disclosed herein comprises a nucleic acid sequence as set forth in any of SEQ ID NOs: 52-86. In some embodiments, a polynucleotide disclosed herein comprises a nucleic acid sequence as shown in Table 2.

[0203] Table 2: Nucleotide sequences for selected peptide candidates

[0204]

[0211] In some embodiments, the polynucleotides disclosed herein can be codon optimized, usage bias has been reported for numerous organisms, from viruses to eukaryotes. Since the genetic code is degenerate (i.e., each amino acid can be coded by on average three different codons), the DNA sequence can be modified by synonymous nucleotide substitutions without altering the amino acid sequence of the encoded protein. Such synonymous codon optimization has been performed for the purpose of optimizing expression in a desired host, as described in the scientific literature and in patent documents. See U.S. Pat. Nos. 5,786,464 and 6,114,14. In some embodiments, the nucleic acid described herein can be modified to improve cloning efficiency. In some embodiments, the nucleic acids described herein are subjected to codon optimization to increase the efficiency of gene expression, e.g., SEQ ID NOs 87-121. are subjected to codon optimization. In some embodiments, the polypeptide disclosed herein are encoded by polynucleotides whose sequence has been codon optimized for expression in a mammalian cell, e.g., expressional in a human cell. Exemplary codon optimized sequences are disclosed in Table 3. In some embodiments, polypeptides encoded by a codon optimized nucleotide have increased expression in a mammalian cell, e.g., a human cell compared to a polypeptide that is encoded by a non-codon optimized polynucleotide.

[0205] Table 3: Codon optimized nucleotide sequences for selected peptide candidates

[0206]

[0212] In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 1, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 52 or 87. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 2, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 53 or 88. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 3, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 54 or 89. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 4, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 55 or 90. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 5, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 56 or 91. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 6, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 57 or 92. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 7, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 58 or 93. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 8, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 59 or 94. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 9, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 60 or 95. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 10, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 61 or 96. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 11, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 62 or 97. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 12, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 63 or 98. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 13, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 64 or 99. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 14, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 65 or 100. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 15, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 66 or 101. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 16, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 67 or 102. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 17, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 68 or 103. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 18, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 69 or 104. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 19, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 70 or 105. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 20, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 71 or 106. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 21, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 72 or 107. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 22, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 73 or 108. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 23, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 74 or 109. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 24, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 75 or 110. . In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 25, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 76 or 111. . In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 26, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 77 or 112. . In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 27, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 78 or 113. . In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 28, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 79 or 114. . In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 29, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 80 or 115. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 30, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 81 or 116. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 31, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 82 or 117. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 32, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 83 or 118. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 33, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 84 or 119. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 34, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 85 or 120. In some embodiments, a polypeptide comprising an amino acid sequence as set forth SEQ ID NO: 35, can be encoded by a polynucleotide having a sequence as set forth in SEQ ID NO: 86 or 121.

[0207]

[0213] In some embodiments, a polynucleotide disclosed herein can encode multiple epitopes, e.g., 2, 3, 4, 5, 6, 7, 8, 9, or 10 epitopes. In some embodiments, the polynucleotide encodes multiple epitopes as discrete peptide epitopes. In some embodiments, the polynucleotide encodes multiple epitopes as poly epitopic peptides. In some embodiments, the epitopes are identical. In some embodiments, the epitopes are different. In some embodiments, a polynucleotide may comprise a sequence encoding at least two or more epitopes described herein, of which both epitopes are the same epitopes. In some embodiments, a polynucleotide may comprise a sequence encoding at least two or more epitopes described herein, of which both epitopes are different epitopes. In a non-limiting example, in some embodiments, a polynucleotide disclosed herein can encode three epitopes e.g., T cell epitopes, e.g., cancer-specific CD8+ and / or CD4+ epitopes, e.g., cancer-specific CD8+ epitopes of which two are the same epitopes and one is a different epitope. In some embodiments, the polynucleotide comprises a nucleotide sequence that encodes spacer amino acid residues between the first and the second epitope.

[0208]

[0214] As will be appreciated by those of skill in the art, in some aspects a nucleic acid comprises regulatory sequences from a plasmid. The nucleic acid sequence can include, for example, one or more of a promoter sequence a selection marker sequence, or a locus-targeting sequence. An example of a promoter that is capable of expressing a transgene in a mammalian T cell is a EFla promoter (SEQ ID NO: 122). The native EFla promoter drives expression of the alpha subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. In some embodiments, the polynucleotide comprises an EFla promoter. Another example of a promoter is the immediate early cytomegalovirus (CMV) promoter sequence. This promoter sequence is a strong constitutive promoter sequence capable of driving high levels of expression of any polynucleotide sequence operatively linked thereto. In some embodiments, the polynucleotide comprises a CMV promoter. In some embodiments, the CMV promoter comprises a sequence with 80-100% sequence identity as that set forth in SEQ ID NO: 36. In some embodiments, the polynucleotide of the present disclosure may comprise a promoter selected from the group consisting of, but not limited to, a simian virus 40 (SV40) early promoter, a mouse mammary tumor virus (MMTV), a human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, a MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus (RSV) promoter, an actin promoter, a myosin promoter, an elongation factor-la promoter, a hemoglobin promoter, and a creatine kinase promoter. In some instances, the polynucleotide comprises a sequence encoding a poly(A) tail. In some instances, the polynucleotide comprises a 3’ UTR sequence. In some instances, the polynucleotide comprises a 5’ UTR sequence. In some embodiments, a polynucleotide disclosed herein comprises multiple smaller and discrete nucleotide sequences that are typically heterologous and exhibit different and measurable function(s), a promoter sequence, a translation initiating sequence, a start codon, a polyadenylation sequence, a stop codon, a nucleotide sequence encoding an epitope, e.g., a T cell epitope, e.g., a cancer-specific CD8+ and / or CD4+ epitope, e.g., a cancer-specific CD8+ epitope, e.g., an epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs 1-35, and / or a linker encoding sequence. In some embodiments, the polynucleotide is codon optimized, e.g., codon optimized for optimal expression in a mammalian cell, e.g., a human cell.

[0209]

[0215] In some embodiments, the polynucleotide, e.g., the RNA, e.g., the mRNA encoding the epitope, e.g., the T cell epitope, e.g., the cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope is introduced into cells. In some embodiments, in vitro transcribed RNA can be introduced to a cell as a form of transient transfection. In some embodiments, the polynucleotide can include some or all of the 5’ and / or 3’ untranslated regions (UTRs). The polynucleotide can include exons and introns. In some embodiments, the DNA to be used for PCR is a human nucleic acid sequence. In some embodiments, the DNA to be used for PCR is a human nucleic acid sequence including the 5’ and 3’ UTRs. The DNA can alternatively be an artificial DNA sequence that is not normally expressed in a naturally occurring organism. An exemplary artificial DNA sequence is one that contains portions of genes that are ligated together to form an open reading frame that encodes a fusion protein. The portions of DNA that are ligated together can be from a single organism or from more than one organism.

[0210]

[0216] Any DNA polymerase useful for PCR can be used in the methods disclosed herein. The reagents and polymerase are commercially available from a number of sources. Chemical structures with the ability to promote stability and / or translation efficiency may also be used. The RNA preferably has 5’ and 3’ UTRs. In some embodiments, the 5’ UTR is between one and 3,000 nucleotides in length. The length of 5’ and 3’ UTR sequences to be added to the coding region can be altered by different methods, including, but not limited to, designing primers for PCR that anneal to different regions of the UTRs. Using this approach, one of ordinary skill in the art can modify the 5’ and 3’ UTR lengths that can be used to achieve optimal translation efficiency following transfection of the transcribed RNA.

[0211]

[0217] The 5’ and 3’ UTRs can be the naturally occurring, endogenous 5’ and 3’ UTRs for the polynucleotide of interest. Alternatively, UTR sequences that are not endogenous to the polynucleotide of interest can be added by incorporating the UTR sequences into the forward and reverse primers or by any other modifications of the template. The use of UTR sequences that are not endogenous to the polynucleotide of interest can be useful for modifying the stability and / or translation efficiency of the RNA. For example, it is known that AU-rich elements in

[0212] 3 ’UTR sequences can decrease the stability of mRNA. Therefore, 3’ UTRs can be selected or designed to increase the stability of the transcribed RNA based on properties of UTRs that are well known in the art.

[0213]

[0218] In some embodiments, the 5’ UTR can contain the Kozak sequence of the endogenous nucleic acid. Alternatively, when a 5’ UTR that is not endogenous to the nucleic acid of interest is being added by PCR as described above, a consensus Kozak sequence can be redesigned by adding the 5’ UTR sequence. Kozak sequences can increase the efficiency of translation of some RNA transcripts. In some embodiments, the 5’ UTR can be 5 ’UTR of an RNA virus whose RNA genome is stable in cells. In some embodiments, various nucleotide analogues can be used in the 3’ or 5’ UTR to impede exonuclease degradation of the mRNA.

[0214]

[0219] In some embodiments, the polynucleotide further comprises a promoter of transcription e.g., a T7 polymerase promoter. Other useful promoters include, but are not limited to, T3 and SP6 RNA polymerase promoters. Consensus nucleotide sequences for T7, T3 and SP6 promoters are known in the art.

[0215]

[0220] In some embodiments, the polynucleotide, e.g., the mRNA has both a cap on the 5’ end and a 3’ poly(A) tail which determine ribosome binding, initiation of translation and stability mRNA in the cell. In some embodiments, the polynucleotide comprises a Poly (A) tail, e.g., a Poly(A) tails providing stability to the mRNA and / or reduce mRNA degradation. In some embodiment, the poly(A) tail is between 100 and 5000 adenosines. In some embodiments, the polynucleotide may comprise immunostimulatory sequences (e.g., ISSs or CpGs).

[0216]

[0221] In some embodiments, the polynucleotide, can also contain an internal ribosome entry site (IRES) sequence. The IRES sequence may be any viral, chromosomal or artificially designed sequence which initiates cap-independent ribosome binding to mRNA and facilitates the initiation of translation. Any solutes suitable for cell electroporation, which can contain factors facilitating cellular permeability and viability such as sugars, peptides, lipids, proteins, antioxidants, and surfactants can be included.

[0217]

[0222] In some embodiments, the polynucleotide of this disclosure can encode any recombinant polypeptide described herein. For example, the polynucleotide can encode a recombinant polypeptide comprising a cancer-specific T cell epitope having a sequence identity of at least about 90-100% to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, or SEQ ID NO: 35. In some embodiments, the polynucleotide can encode a recombinant polypeptide having at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more amino acid residues of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, or SEQ ID NO: 35. In some embodiments, the polynucleotide can encode a recombinant polypeptide having at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or more amino acid substitutions of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, or SEQ ID NO: 35.

[0218]

[0223] In some embodiments, the polynucleotide encodes a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope that can bind to an HLA molecule e.g., an HLA-A allele, e.g., an HLA-B allele, e.g., an HLA-C allele. In some embodiments the HLA-A allele is an HLA-A*15 allele, (e.g., an HLA-A*15:01 allele), an HLA-A*02 allele (e.g., an HLA-A*02:01 allele, e.g., an HLA-A*02:05 allele), an HLA-A*03 allele (e.g., an HLA-A*03:01 allele,, an HLA-A* 11 allele (e.g., an HLA-A* 11 :01 allele), or an HLA-A*31 allele (e.g., an HLA-A*31 :01 allele). In some embodiments the HLA-B allele is an HLA-B*07 allele (e.g., an HLA-B*07:02 allele), an HLA-B*08 allele (e.g., an HLA-B*08:01 allele), an HLA-B*15 allele (e.g., an HLA- B*15:01 allele), an HLA-B*18 allele (e.g., an HLA-B*18:01 allele), an HLA-B*35 allele (e.g., an HLA-B*35:01 allele, an HLA-B*35:03 allele), an HLA-B*40 allele (e.g., an HLA-B*40:01 allele, an HLA-B*40:02 allele), or an HLA-B*44 allele (e.g., an HLA-B*44:01 allele, e.g., an HLA-B*44:02 allele). In some embodiments the HLA-C allele is an HLA-C*03 allele, (e.g. an HLA-C*03:04 allele), or an HLA-C*07 allele, (e.g., an HLA-C*07:01 allele, e.g., an HLA- C*07:02 allele).

[0219]

[0224] The nucleotide sequence encoding an epitope e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope may comprise from approximately 12 to approximately 45 base pairs, e.g., approximately 15 to

[0220] -SO- approximately 45 base pairs, approximately 18 to approximately 45 base pairs, approximately 21 to approximately 45 base pairs, approximately 24 to approximately 45 base pairs.

[0221]

[0225] In some embodiments, a polynucleotide disclosed herein can be a spherical nucleic acid (SNA). In some embodiments, an SNA disclosed herein comprises a nanoparticle conjugated with a polynucleotide sequence disclosed herein. In some embodiments, a SNA disclosed herein comprises an unilamellar liposome core. In some embodiments, a SNA disclosed herein comprises one or more CpG oligonucleotides. In some embodiments, an SNA disclosed herein comprises a polynucleotide, e.g., a polynucleotide comprising any of SEQ ID NOs: 52-121 encapsulated within the liposome core. In some embodiments, a polynucleotide, e.g., a polynucleotide comprising any of SEQ ID NOs: 52-121 is located on the surface of an SNA disclosed herein. In some embodiments, a polynucleotide, e.g., a polynucleotide comprising any of SEQ ID NOs: 52121 is chemically conjugated to the liposomal surface of an SNA disclosed herein. In some embodiments, a polynucleotide, e.g., a polynucleotide comprising any of SEQ ID NOs: 52121 is hybridized to one or more CpG oligonucleotides and adsorbed to the liposome surface. In some embodiments, an SNA disclosed herein can be a liposomal SNA.

[0222] Vectors

[0223]

[0226] In one aspect, the disclosure provides a vector, e.g., a vector comprising a recombinant polypeptide described herein, a vector comprising a polynucleotide encoding a recombinant polypeptide described herein. In some embodiments, the vector is a viral vector. In some embodiments, the vector is a non-viral vector.

[0224]

[0227] In some embodiments, a viral vector can be an adenovirus vector, an adeno-associated virus (AAV) vector (e.g., AAV type 5 and type 2), an alphavirus vectors (e.g., Venezuelan equine encephalitis virus (VEE), a sindbis virus (SIN), semliki forest virus (SFV), and VEE-SIN chimeras), a flaviviral vector, a herpes virus vector (e.g. vectors derived from cytomegaloviruses, like rhesus cytomegalovirus (RhCMV), an arena virus vector (e.g. lymphocytic choriomeningitis virus (LCMV) vectors), a measles virus vector, a BCG vector, a vaccinia vector, a papillomaviral vector, and a poxvirus vector.

[0225]

[0228] In some embodiments, the vector comprises an adenoviral vector. In some embodiments, the adenoviral vector can be or derived from a human adenovirus vector, a simian adenovirus, etc., or comprises a species B adenovirus vector (e.g., Ad3, 1 Ip, and 35), a species C adenovirus vector (e.g., Adi, Ad 2, Ad5 and Ad6), a species E adenovirus vector (e.g., Ad4), a species F adenovirus vector (e.g., Ad41) or a chimeric Ad5 vector comprising the Adil or Ad35 fibers (Ad5 / 11 and Ad5 / 35). an adenovirus 6 vector, a PanAd3 vector, or an adenovirus C3 vector. In some embodiments, the adenoviral vector is a human serotype 5 (AdHu5). In some embodiments the vector may be an animal derived adenoviral vector for example canine, simian in particular rhesus monkey and chimpanzee. In some embodiments, the adenoviral vector may be a rare serotype vector derived from a non-human primate. Vectors derived from chimpanzee may be suitable for the vector for the present disclosure, examples include but are not limited to ChAd63, ChAd3, ChAdY25.

[0226]

[0229] In some embodiments, the vector is an adenoviral vector, e.g., an adenoviral vector comprising a polynucleotide sequence encoding a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, optionally wherein the vector is capable of inducing an inflating memory CD8+ T cell response. In some embodiments, the adenoviral vector comprises a polynucleotide sequence encoding a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, and the vector does not comprise any additional cancer specific CD8+ T cell epitopes. In some embodiments, the adenoviral vector comprises a polynucleotide sequence encoding multiple epitopes, e.g., multiple T cell epitopes, e.g., multiple cancer-specific CD8+ epitopes.

[0227]

[0230] In some embodiments, the vector is or comprises an AAV vector. In some embodiments, the AAV vector may be an AAV1, AAV2, AAVS or any combination thereof. In some embodiments, the AAV vector is selected for delivery to a particular cell, tissue, or organ, e.g., AAV serotypes 1, 2, 5 or a hybrid capsid AAV1, AAV2, AAVS or any combination thereof for targeting brain or neuronal cells; AAV4 for targeting cardiac tissue, and AAV8 for delivery to the liver.

[0228]

[0231] In some embodiments, the vector may be modified to reduce the immunogenicity and improve biosafety of the vector. In some embodiments, the vector may be replication-deficient. In some embodiments, the vector may lack the El and E3 proteins.

[0229]

[0232] In some embodiments, the vector may be a recombinant (e.g., engineered) adenoviral vector, wherein the backbone of the recombinant adenoviral vector is an adenovirus serotype 5 (Ad5) nucleic acid backbone. The recombinant adenoviral vector may comprise a deletion or a functional deletion of an El gene. The recombinant adenoviral vector may comprise a deletion or a functional deletion of an E3 gene. The recombinant adenoviral vector may comprise a deletion or a functional deletion of the El and E3 genes. The recombinant adenoviral vector may comprise a transgene inserted at the locus of the deleted or functionally deleted El gene. The recombinant adenoviral vector may comprise a transgene inserted at the locus of the deleted or functionally deleted E3 gene. The transgene insertion may comprise a single cancer-specific CD8+ T cell epitope described herein. The transgene insertion may comprise a single cancer- specific CD4+ T cell epitope described herein. The transgene insertion may comprise more than one cancer-specific CD4+ T cell epitope. The transgene insertion may comprise a cancer-specific CD8+ T cell epitope and a cancer-specific CD4+ T cell epitope. A nucleic acid sequence encoding the single cancer-specific CD8+ T cell epitope may be inserted in the El region.

[0230]

[0233] In some embodiments, the vector further comprises a promoter. In some embodiments, the vector is an in vitro transcribed vector. In some embodiments, the vector may comprise a strong promoter, examples include but are not limited to a CMV promoter, an RSV promoter, an EFla promoter, a simian virus 40 (SV40) early promoter, a mouse mammary tumor virus (MMTV), a human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter, a MoMuLV promoter, an avian leukemia virus promoter, an Epstein-Barr virus immediate early promoter, a Rous sarcoma virus (RSV) promoter, as well as human gene promoters such as, but not limited to, the actin promoter, the myosin promoter, the elongation factor-la promoter, the hemoglobin promoter, and the creatine kinase promoter. In some embodiments, the vector comprises a CMV promoter. An exemplary sequence for a CMV promotor is provided in SEQ ID NO:31.

[0231]

[0234] In some embodiments, the vector may comprise an inducible promoter. Examples of inducible promoters include, but are not limited to a metallothionine promoter, a glucocorticoid promoter, a progesterone promoter, and a tetracycline-regulated promoter.

[0232]

[0235] In some embodiments, a vector disclosed herein can comprise additional promoter elements, e.g., enhancers and / or silencers.

[0233]

[0236] In some embodiments, the vector may comprise a TATA box. In some embodiments, the vector comprises a translation initiation sequence, for example a Kozak sequence. A Kozak sequence has the consensus sequence (gcc)gccRccAUGG, a suitable Kozak sequence is provided in SEQ ID NO: 37. In some embodiments, the vector comprises a termination sequence and / or a polyadenylation sequence. A suitable polyadenylation sequence is provided in SEQ ID NO: 43. The AAV vector may comprise inverted terminal repeat (ITR) sequences. A suitable 3’ ITR sequence is provided in SEQ ID NO: 51. A suitable 5’ ITR sequence is provided in SEQ ID NO: 50.

[0234]

[0237] In some embodiments, the viral vector comprises the vector back bone, a promoter region and a nucleotide sequence encoding a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope.

[0235]

[0238] In some embodiments, the ITR sequences flank the encoded the epitope, e.g., the T cell epitope, e.g., the cancer-specific CD8+ and / or CD4+ epitope, e.g., the cancer-specific CD8+ epitope. In some embodiments, there may be an ITR sequence present 5’ to the cancer specific epitope. In some embodiments, there may be an ITR sequence 3’ to the cancer specific epitope. In some embodiments, there may be an ITR sequence present 5’ to the cancer specific epitope and / or an ITR sequence 3’ to the cancer specific epitope. In some embodiments, the 5’ ITR sequence may comprise SEQ ID NO: 50. In some embodiments, the 3’ ITR sequence may comprise SEQ ID NO: 51. In some embodiments, the vector may comprise sequences 5’ to the cancer specific epitope for example SEQ ID NOs: 44 or 47. In some embodiments, the vector may comprise sequences 3’ to the cancer specific epitope for example SEQ ID NOs: 45 or 48. In some embodiments, in order to produce the viral vector comprising the cancer specific CD8+ T cell epitope, helper plasmids may be used. In some embodiments, a helper plasmid or plasmids may be used to provide genes required for viral vector replication or packaging. In some embodiments, helper plasmid encodes E2A, E4 and VA adenoviral proteins and or encodes the rep and cap genes of AAV. In some embodiments, the vector may comprise a sequence as set forth in SEQ ID NOs: 46 or 49.

[0236]

[0239] In some embodiments, the vector may be modified to reduce the immunogenicity and improve biosafety of the vector. In some embodiments, the vector may be replication-deficient. In some embodiments, the vector may lack the El and E3 proteins. The vector may comprise sequences 5’ to the cancer specific epitope for example SEQ ID NOs: 44 or 47. The vector may comprise sequences 3’ to the cancer specific epitope for example SEQ ID NOs: 45 or 48.

[0237]

[0240] In some embodiments, a vector may also be derived from retroviruses such as the lentivirus. In some embodiments, a vector disclosed herein, e.g., a lentiviral vector can transduce non-proliferating cells, such as hepatocytes. In some embodiments, a vector disclosed herein has low immunogenicity.

[0238]

[0241] The term “lentivirus” refers to a genus of the Retroviridae family. Lentiviruses are unique among the retroviruses in being able to infect non-dividing cells; they can deliver a significant amount of genetic information into the DNA of the host cell, so they are one of the most efficient methods of a gene delivery vector. HIV, SIV, and FIV are all examples of lentiviruses.

[0239]

[0242] The term “lentiviral vector” refers to a vector derived from at least a portion of a lentivirus genome, including especially a self-inactivating lentiviral vector as provided in Milone et al., Mol. Ther. 17(8): 1453-1464 (2009). Other examples of lentivirus vectors that may be used in the clinic, include but are not limited to, e.g., the LENTIVECTOR TM gene delivery technology from Oxford BioMedica, the LENTIMAXTM vector system from Lentigen, and the like. Nonclinical types of lentiviral vectors are also available and would be known to one skilled in the art.

[0243] The recombinant polypeptide described herein may be used in multi ci str onic vectors or vectors expressing several polypeptides in the same transcriptional unit. Such vectors may use internal ribosomal entry sites (IRES). Since IRES are not functional in all hosts and do not allow for the stoichiometric expression of multiple protein, self-cleaving peptides may be used instead. For example, several viral peptides are cleaved during translation and allow for the expression of multiple proteins form a single transcriptional unit. Such peptides include 2A-peptides, or 2A- like sequences, from members of the Picornaviridae virus family. See for example Szymczak et al., 2004, Nature Biotechnology; 22:589- 594. In some embodiments, the recombinant nucleic acid described herein encodes the recombinant polypeptide in frame with the agent, with the two sequences separated by a self-cleaving peptide, such as a 2A sequence, or a T2A sequence.

[0240]

[0244] In some embodiments, a vector disclosed herein can also contain a selectable marker gene and / or a reporter gene or both. In some embodiments, the selectable marker may be carried on a separate piece of DNA and used in a co-transfection procedure. Both selectable markers and reporter genes may be flanked with appropriate regulatory sequences to enable expression in the host cells. Useful selectable markers include, for example, antibiotic-resistance genes, such as neo and the like.

[0241]

[0245] Reporter genes are used for identifying potentially transfected cells and for evaluating the functionality of regulatory sequences. In general, a reporter gene is a gene that is not present in or expressed by the recipient organism or tissue and that encodes a polypeptide whose expression is manifested by some easily detectable property, e.g., enzymatic activity. Expression of the reporter gene is assayed at a suitable time after the DNA has been introduced into the recipient cells. Suitable reporter genes may include genes encoding luciferase, beta-galactosidase, chloramphenicol acetyl transferase, secreted alkaline phosphatase, or the green fluorescent protein gene (e.g., Ui-Tei et al., 2000 FEBS Leters 479: 79-82). Suitable expression systems are well known and may be prepared using known techniques or obtained commercially. In general, the construct with the minimal 5’ flanking region showing the highest level of expression of reporter gene is identified as the promoter. Such promoter regions may be linked to a reporter gene and used to evaluate agents for the ability to modulate promoter-driven transcription.

[0242]

[0246] In some embodiments, the vector is a non-viral vector, e.g., a plasmid, a cosmid, a viruslike particle, a bacterial vector, an artificial chromosome, a liposome, a lipid nanoparticle, or an exosome. In some embodiments, the vector is a bacterial vector, e.g., an attenuated Salmonella typhimurium, Salmonella typhi, Shigella, Bacillus, Lactobacillus, Bacille Calmette-Guerin (BCG), E. coli, Vibrio cholerae, Campylobacter, Listeria. In some embodiments, the vector is an attenuated and / or a non- pathogenic vector.

[0247] In the case where a non-viral vector is utilized, an exemplary non-viral vector is a liposome. The use of lipid formulations is contemplated for the introduction of the nucleic acids into a host cell (in vitro, ex vivo or in vivo). In another aspect, the nucleic acid may be associated with a lipid. The nucleic acid associated with a lipid may be encapsulated in the aqueous interior of a liposome, interspersed within the lipid bilayer of a liposome, attached to a liposome via a linking molecule that is associated with both the liposome and the oligonucleotide, entrapped in a liposome, complexed with a liposome, dispersed in a solution containing a lipid, mixed with a lipid, combined with a lipid, contained as a suspension in a lipid, contained or complexed with a micelle, or otherwise associated with a lipid. Lipid, lipid / DNA or lipid / vector associated compositions are not limited to any particular structure in solution. For example, they may be present in a bilayer structure, as micelles, or with a “collapsed” structure. They may also simply be interspersed in a solution, possibly forming aggregates that are not uniform in size or shape. Lipids are fatty substances which may be naturally occurring or synthetic lipids. For example, lipids include the fatty droplets that naturally occur in the cytoplasm as well as the class of compounds which contain long-chain aliphatic hydrocarbons and their derivatives, such as fatty acids, alcohols, amines, amino alcohols, and aldehydes.

[0243]

[0248] Lipids suitable for use can be obtained from commercial sources. For example, dimyristyl phosphatidylcholine (“D1VIPC”) can be obtained from Sigma, St. Louis, Mo.; dicetyl phosphate (“DCP”) can be obtained from K & K Laboratories (Plainview, N. Y.); cholesterol (“Choi”) can be obtained from Calbiochem-Behring; dimyristyl phosphatidylglycerol (“DMPG”) and other lipids may be obtained from Avanti Polar Lipids, Inc. (Birmingham, Ala.). Stock solutions of lipids in chloroform or chloroform / methanol can be stored at about -20 °C. Chloroform is used as the only solvent since it is more readily evaporated than methanol. “Liposome” is a generic term encompassing a variety of single and multilamellar lipid vehicles formed by the generation of enclosed lipid bilayers or aggregates. Liposomes can be characterized as having vesicular structures with a phospholipid bilayer membrane and an inner aqueous medium. Multilamellar liposomes have multiple lipid layers separated by aqueous medium. They form spontaneously when phospholipids are suspended in an excess of aqueous solution. The lipid components undergo self-rearrangement before the formation of closed structures and entrap water and dissolved solutes between the lipid bilayers (Ghosh et al., 1991 Glycobiology 5: 505-10). However, compositions that have different structures in solution than the normal vesicular structure are also encompassed. For example, the lipids may assume a micellar structure or merely exist as nonuniform aggregates of lipid molecules. Also contemplated are lipofectamine-nucleic acid complexes.

[0249] In some embodiments, the polynucleotide of the present disclosure can be cloned into a number of types of vectors. For example, the polynucleotide can be cloned into a vector including, but not limited to a plasmid, a phagemid, a phage derivative, a virus, and a cosmid. In some embodiments, the polynucleotide can be cloned into a vector including, but not limited to an expression vector, a replication vector, a probe generation vector, and a sequencing vector. In some embodiments, a vector disclosed herein comprises a recombinant polypeptide disclosed herein, e.g., a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35. In some embodiments, a vector disclosed herein comprises a polynucleotide disclosed herein, e.g., a polynucleotide encoding a recombinant polypeptide disclosed herein, e.g., a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.

[0244]

[0250] In some embodiments, the vector comprises a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35.

[0245]

[0251] In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 1. In some embodiments, the vector can encode a single cancerspecific CD8+ T cell epitope as set forth in SEQ ID NO: 2. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 3. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 4. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 5. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 6. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 7. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 8. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 9. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 10. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 11. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 12. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 13. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 14. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 15. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 16. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 17. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 18. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 19. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 20. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 21. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 22. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 23. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 24. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 25. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 26. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 27. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 28. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 29. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 30. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 31. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 32. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 33. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 34. In some embodiments, the vector can encode a single cancer-specific CD8+ T cell epitope as set forth in SEQ ID NO: 35.

[0252] In some embodiments, the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising approximately 5 to approximately 15 amino acids, approximately 6 to approximately 15 amino acids, approximately 7 to approximately 15 amino acids, or approximately 8 to approximately 15 amino acids.

[0253] In some embodiments, the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, and HELGFKVVL. In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and / or CD4+ T cell epitopes selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, and HELGFKVVL, or any combination thereof.

[0246]

[0254] In some embodiments, the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, and RPASPRPAP. In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and / or CD4+ T cell epitopes selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, and RPASPRPAP, or any combination thereof.

[0247]

[0255] In some embodiments, the vector encodes a single epitope, e.g., a single T cell epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, IYPFINSH, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, and VVAAHLAGA. In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and / or CD4+ T cell epitopes selected from GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, GPRPSPTRSV, GQHLHLETF, SPRSPSPSL, VPQEAVRAPL, IYPFINSH, SPSSASLTL, LNKVKTSL, NLKTHLRL, FRGVFVHRY, TSGPVTEKY, and VVAAHLAGA or any combinations thereof. In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancerspecific CD8+ and / or CD4+ T cell epitopes selected from SEQ ID NOs 1-6 or any combinations thereof. In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and / or CD4+ T cell epitopes selected from SEQ ID NOs 7-12 or any combinations thereof In some embodiments, the vector encodes two or more (e.g., 2, 3, 4, 5, 6, or more) cancer-specific CD8+ and / or CD4+ T cell epitopes selected from SEQ ID NOs 13-18 or any combinations thereof In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV.

[0248]

[0256] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL.

[0249]

[0257] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL.

[0250]

[0258] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL.

[0251]

[0259] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL.

[0252]

[0260] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL.

[0253]

[0261] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL.

[0254]

[0262] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL.

[0255]

[0263] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer- specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL.

[0256]

[0264] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL.

[0257]

[0265] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL.

[0258]

[0266] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL.

[0259]

[0267] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL.

[0268] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL.

[0260]

[0269] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL.

[0261]

[0270] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL.

[0262]

[0271] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL.

[0263]

[0272] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL.

[0264]

[0273] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL.

[0265]

[0274] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL.

[0266]

[0275] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL.

[0267]

[0276] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL.

[0268]

[0277] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.

[0269]

[0278] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL.

[0270]

[0279] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL.

[0271]

[0280] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL.

[0272]

[0281] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL.

[0273]

[0282] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL.

[0274]

[0283] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL.

[0284] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.

[0275]

[0285] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and HELGFKVVL.

[0276]

[0286] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL.

[0277]

[0287] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KEFAFLEHSL.

[0278]

[0288] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and HELGFKVVL.

[0279]

[0289] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL.

[0280]

[0290] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL.

[0281]

[0291] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and HELGFKVVL.

[0282]

[0292] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.

[0283]

[0293] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and HELGFKVVL.

[0284]

[0294] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and HELGFKVVL.

[0285]

[0295] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, wherein the at least three cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0286]

[0296] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL.

[0287]

[0297] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL.

[0288]

[0298] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and HELGFKVVL.

[0299] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.

[0289]

[0300] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.

[0290]

[0301] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0291]

[0302] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.

[0292]

[0303] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.

[0293]

[0304] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0294]

[0305] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least four cancer-specific CD8+ T cell epitopes, wherein the at least four cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0295]

[0306] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL.

[0296]

[0307] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and HELGFKVVL.

[0297]

[0308] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0298]

[0309] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0299]

[0310] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0300]

[0311] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0301]

[0312] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least five cancer-specific CD8+ T cell epitopes, wherein the at least five cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KEFAFLEHSL and HELGFKVVL.

[0302]

[0313] In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL. In some embodiments, the vector comprises: (i) a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least six cancer-specific CD8+ T cell epitopes, wherein the at least six cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and KPRPDVTNEL and KEFAFLEHSL and HELGFKVVL.

[0303]

[0314] In some embodiments, the vector comprises a sequence with at least 90% sequence identity to SEQ ID NO: 44 and a sequence with at least 90% sequence identity to SEQ ID NO: 45. In some embodiments, the vector further comprises a sequence with at least 90% sequence identity to SEQ ID NO: 47 and a sequence with at least 90% sequence identity to SEQ ID NO: 48.

[0304]

[0315] Cancer specific CD8+ T cell epitopes may be determined using techniques know in the art such as proteomics approaches, mass spectrometry approaches, genomic approaches, transcriptome analysis, bioinformatics approaches and in silico methods. It would be possible for the skilled person to select an appropriate epitope to be encoded within the vector of the present disclosure.

[0305]

[0316] Methods of introducing and expressing genes into a cell are known in the art. In the context of a vector, the vector can be readily introduced into a host cell, e.g., mammalian, bacterial, yeast, or insect cell by any method in the art. For example, the vector can be transferred into a host cell by physical, chemical, or biological means.

[0306]

[0317] Physical methods for introducing a polynucleotide into a host cell include calcium phosphate precipitation, lipofection, particle bombardment, microinjection, electroporation, polymer encapsulation, peptide mediated transfection, or biolistic particle delivery systems such as “gene guns” and the like. Methods for producing cells comprising vectors and / or exogenous nucleic acids are well-known in the art. See, for example, Sambrook et al., 2012, Molecular Cloning: A Laboratory Manual, volumes 1-4, Cold Spring Harbor Press, NY). A non-limiting example for the introduction of a polynucleotide into a host cell is calcium phosphate transfection.

[0307]

[0318] Biological methods for introducing a polynucleotide of interest into a host cell include the use of DNA and RNA vectors. Viral vectors, and especially retroviral vectors, have become the most widely used method for inserting genes into mammalian, e.g., human cells. Other viral vectors can be derived from lentivirus, poxviruses, herpes simplex virus I, adenoviruses and adeno-associated viruses, and the like (see, e.g., U.S. Pat. Nos. 5,350,674 and 5,585,362.

[0308]

[0319] Chemical means for introducing a polynucleotide into a host cell include colloidal dispersion systems, such as macromolecule complexes, nanocapsules, nanoparticles, lipid nanoparticle conjugates, microspheres, beads, and lipid-based systems including oil-in-water emulsions, micelles, mixed micelles, and liposomes. An exemplary colloidal system for use as a delivery vehicle in vitro and in vivo is a liposome (e.g., an artificial membrane vesicle). Other methods of state-of-the-art targeted delivery of nucleic acids are available, such as delivery of polynucleotides with targeted nanoparticles or other suitable sub-micron sized delivery system.

[0309]

[0320] Regardless of the method used to introduce exogenous nucleic acids into a host cell or otherwise expose a cell to the inhibitor of the present disclosure, in order to confirm the presence of the recombinant DNA sequence in the host cell, a variety of assays may be performed. Such assays include, for example, “molecular biological” assays well known to those of skill in the art, such as Southern and Northern blotting, RT-PCR and PCR; “biochemical” assays, such as detecting the presence or absence of a particular peptide, e.g., by immunological means (ELISAs and western blots) or by assays described herein to identify agents falling within the scope of the present disclosure.

[0310] Cells and Populations of Cells

[0311]

[0321] In one aspect, the present disclosure provides a cell comprising (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35. In some embodiments, the cell can be an antigen presenting cell (APC). In some embodiments, the cell can be a T cell stimulated with an APC described herein. In some embodiments, the cell comprises a CD8+ T cell. In some embodiments, the cell comprises a CD4+ T cell. In some embodiments, the cell is an inflating memory T cell, e.g., an inflating memory CD8+ T cell.

[0312]

[0322] In one aspect, the present disclosure provides a population of cells wherein a cell in the population comprises (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35. In some embodiments, the population of cells comprises a plurality of APCs. In some embodiments, the plurality of APCs comprise (i) a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ epitope, e.g., a single cancer-specific CD8+ epitope comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35. In some embodiments, the population of cells comprises a plurality of T cells stimulated with an APC described herein. In some embodiments, the population of cells comprises a plurality of CD8+ T cells. In some embodiments, the population of cells comprises a plurality of CD4+ T cells. In some embodiments, the population of cells comprises a plurality of inflating memory T cells, e.g., inflating memory CD8+ T cells.

[0313]

[0323] Inflating memory T cells described herein can be characterized by the presences of specific markers and cell surface markers. Methods to identify and quantify these markers are well known in the art. Examples of suitable methods include but are not limited to affinity -based separation methods, magnetic cell sorting techniques, fluorescence-based cell sorting techniques such as FACS (fluorescence activated cell sorting). The inflating memory CD8+ T cells can be characterized by the presence of a number of markers, examples include but are not limited to CX3CR1, KLRG-1, CD44. The inflating memory CD8+ T cells can also be characterized by the low expression of a number of markers, example include but are not limited to CD62L, CD27, CD127. The term “low expression” may refer to cells wherein there is no expression of the markers, it may also refer to cells wherein there is low expression of the markers relative to other cells in the sample. In some embodiments, the population of cells comprises a plurality of inflating memory T cells, e.g., a plurality of inflating memory CD8+ T cells, e.g., a plurality of inflating memory CD8+ T cells wherein an inflating memory CD8+ T cell of the population expresses one or more of CX3CR1, KLRG-1, CD44 and / or have low expression of one or more of CD62L, CD27, CD 127.

[0314]

[0324] In some embodiments, the inflating memory CD8+ T cells described herein are characterized by markers selected from the group comprising CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+ / - wherein the designation (+) indicates the presence of the marker, and the designation (-) indicates low expression or no expression of the marker; wherein the (-)

[0315] -n- designation means low expression this may be further indicated by “(low)”. In some embodiments, the inflating memory CD8+ T cells may be characterized by one or more markers selected from the group comprising CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+ / -, CD27-(low), and / or CD127-(low). In some embodiments, the inflating memory CD8+ T cells may be characterized by the phenotype CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+ / -. The inflating memory CD8+ T cells may be characterized by the phenotype CX3CR1+, KLRG-1+, CD44+, CD62L-, CCR7-, CD45RA+ / -, CD27-(low), CD 127- (low). The CD8+ T cells produced in an inflating memory response may have a number of other characteristics. For example, the cells may comprise a transcriptional profile driven by Tbx21 (also referred to as T-bet). These cells show a sustained expression of Tbx21. The cells may also show a sustained expression of E2f2 a transcription factor generally involved in cell growth and proliferation. The cells may also lack expression or have low expression of the transcription factor Eomes. In some embodiments, the cell comprising a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, comprises a transcriptional profile driven by Tbx21. In some embodiments, the cell comprising a recombinant polypeptide comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope, comprises a sustained expression of E2f2. In some embodiments, the cell comprising a single epitope, e.g., a single T cell epitope, e.g., a single cancer-specific CD8+ and / or CD4+ epitope, e.g., a single cancer-specific CD8+ epitope comprises a low expression of the transcription factor Eomes.

[0316]

[0325] The inflating memory CD8+ T cells may not demonstrate classical contraction after exposure to an antigen. During classical memory evolution after exposure to an antigen, the cells form a contracted central memory pool which makes up <1% of total circulating CD8+ T cells. However, inflating memory cells are maintained as large pools of cells which circulate in the blood. As such, the resulting inflating memory CD8+ T cells form approximately 0.01% to approximately 20% of total CD8+ T cells. In some embodiments, the population of inflating memory CD8+ T cells comprises 0.01%, 0.02%, 0.03%, 0.05%, 0.07%, 0.09%, 0.1%, 0.3%, 0.5%, 0.7%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, or 20% of total CD8+ T cells. In some embodiments, the population of inflating memory CD8+ T cells comprises approximately 0.1% to approximately 20%, approximately 0.05% to approximately 20%, approximately 0.5% to approximately 20%, approximately 1% to approximately 20%, approximately 2% to approximately 20%, approximately 3% to approximately 20%, approximately 5% to approximately 20%, approximately 8% to approximately 20%, approximately 10% to approximately 20%, approximately 12% to approximately 20%, approximately 15% to approximately 20%, or approximately 18% to approximately 20% of total CD8+ T cells. In some embodiments, the population of inflating memory CD8+ T cells comprises approximately 12% to approximately 20% of total CD8+ T cells.

[0317]

[0326] In some cases, the population of inflating memory CD8+ T cells can retain their effector memory phenotype. The resulting inflating memory CD8+ T cells can retain their memory effector phenotype for a prolonged period, wherein the effector phenotype is characterized by CD44+ and / or CD62L-. The inflating memory CD8+ T cells may retain their memory effector phenotype for up to 60 days post exposure to the vector of the present disclosure. In some embodiments, the population of inflating memory CD8+ T cells may retain their memory effector phenotype for up to 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours, 24 hours or longer post exposure to the vector of the present disclosure. In some embodiments, the population of inflating memory CD8+ T cells may retain their memory effector phenotype for up to 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 15 days, 17 days, 20 days, 25 days, 30 days, 35 days, 40 days, 50 days, 55 days, 60 days or longer post exposure to the vector of the present disclosure.

[0318]

[0327] The inflating memory CD8+ T cells may lack markers of exhaustion. T cell exhaustion can occur from excessive TCR (T cell receptor) stimulation. Markers of T cell exhaustion can include but are not limited to upregulation of markers such as PD-1, Tim-3, or Lag-3. As such, in some embodiments, the inflating memory CD8+ T cells may lack or demonstrate low expression of markers selected from the group consisting of, but not limited to, PD-1, Tim-3, and / or Lag-3.

[0319]

[0328] In some embodiments, the T cells describe herein can demonstrate a distinct transcriptional profile from both central memory and exhausted memory T cell subsets. In some embodiments, the T cells describe herein can demonstrate features such as enhanced redox resilience which may be due to intrinsically lower levels of reactive oxygen species and resilience to oxidative stress. In some embodiments, the transcriptional profile is driven by the transcription factor Tbx21 with minimal contribution from Eomes. This results in a CD8+ T cell phenotype that is long lived, and present in the peripheral organs in high numbers whilst retaining effector function. In some embodiments, the antigen-specific inflating memory CD8+ T cells develop through one or more of processing, presentation and co-stimulation conditions. In some embodiments, the processing of the epitope occurs independently of the proteasome or immunoproteasome and optionally presentation by a non-hematopoietic unconventional APC during the later stages can help to preserve this phenotype. In some embodiments, using a vector which encodes (i) a recombinant polypeptide comprising one or more epitopes, e.g., one or more T cell epitopes, e.g., one or more cancer-specific CD8+ epitopes, e.g., one or more cancerspecific CD8+ epitopes, each comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising one or more epitopes, e.g., one or more T cell epitopes, e.g., one or more cancer-specific CD8+ epitopes, e.g., one or more cancer-specific CD8+ epitopes, each comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, the antigen processing requirements can be bypassed. In some embodiments, using a vector which encodes (i) a recombinant polypeptide comprising one or more epitopes, e.g., one or more T cell epitopes, e.g., one or more cancer-specific CD8+ epitopes, e.g., one or more cancer-specific CD8+ epitopes, each comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, or (ii) a polynucleotide encoding a recombinant polypeptide comprising one or more epitopes, e.g., one or more T cell epitopes, e.g., one or more cancer-specific CD8+ epitopes, e.g., one or more cancer-specific CD8+ epitopes, each comprising an amino acid sequence as set forth in any of SEQ ID NOs: 1-35, induces an inflating memory response.

[0320] Compositions

[0321]

[0329] In one aspect, the present disclosure provides a composition, e.g., a therapeutic composition. In some embodiments, the composition, e.g., the therapeutic composition induces an inflating memory CD8+ T cell response (i.e., a sustained, functional, durable CD8+ T cell response). In some embodiments, the resulting pool of CD8+ T cells are able to resist exhaustion which can occur due to prolonged TCR stimulation.

[0322]

[0330] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is GVYDGREHTV. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0323] (iii); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is GVYDGREHTV and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele.

[0324]

[0331] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),

[0325] (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KLVELEHTL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0326] (iii); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KLVELEHTL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele.

[0327]

[0332] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),

[0328] (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is SPSSASLAL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0329] (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele and / or an HLA-B*35:03 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele and / or an HLA-B*35:03 allele.

[0330]

[0333] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),

[0331] (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0332] (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- C*07:02 allele, or any combination thereof.

[0333]

[0334] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:01 allele, an HLA-B*40:02 allele, an HLA-B*44:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*44:02 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:01 allele, an HLA-B*40:02 allele, an HLA-B*44:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*44:02 allele.

[0334]

[0335] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),

[0335] (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0336] (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*18:01 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*40:01 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope(iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*44:02 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B* 18:01 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:01 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*44:02 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*40:02 allele.

[0337]

[0336] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancer-specific CD8+ T cell epitope is NLRPPTQEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i),

[0338] (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is NLRPPTQEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0339] (iii); wherein the cancer-specific CD8+ T cell epitope is NLRPPTQEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-C*03:03 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of a cancer-specific CD8+ T cell epitope, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the cancerspecific CD8+ T cell epitope is NLRPPTQEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-C*03:03 allele, or any combination thereof.

[0340]

[0337] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele.

[0341]

[0338] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof.

[0342]

[0339] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA- B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.

[0343]

[0340] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA- B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0344]

[0341] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B* 18:01 allele an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are GVYDGREHTV and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA- B*40:01 allele, an HLA-B *44: 02 allele, an HLA-B *40: 02 allele, or any combination thereof.

[0342] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof.

[0345]

[0343] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA- B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.

[0346]

[0344] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii),

[0347] (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or

[0348] (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0345] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA- B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0349]

[0346] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii),

[0350] (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.

[0351]

[0347] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or

[0352] (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer- specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii),

[0353] (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0348] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or

[0354] (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancerspecific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA- B* 18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0355]

[0349] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0356]

[0350] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KPRPDVTNEL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA- B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0357]

[0351] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancerspecific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least two cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least two cancer-specific CD8+ T cell epitopes are KEFAFLEHSL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-B* 18:01 allele, an HLA-B*40:01 allele, an HLA- B*44:02 allele, an HLA-B *40: 02 allele, or any combination thereof.

[0358]

[0352] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL. In some embodiments, the therapeutic composition comprises:

[0359] (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or

[0360] (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancerspecific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0361] (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL. In some embodiments, the therapeutic composition comprises:

[0362] (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or

[0363] (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancerspecific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or

[0364] (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and SPSSASLAL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA- B*07:02 allele, an HLA-B*35:03 allele, or any combination thereof.

[0365]

[0353] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.

[0366]

[0354] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0367]

[0355] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and KLVELEHTL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0368]

[0356] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancerspecific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KPRPDVTNEL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-C*07:02 allele, or any combination thereof.

[0369]

[0357] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer- specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and KEFAFLEHSL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof.

[0370]

[0358] In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide comprising at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APCs comprising (i), (ii), or (iii); wherein the at least three cancer-specific CD8+ T cell epitopes are GVYDGREHTV and SPSSASLAL and HELGFKVVL and wherein the composition is for use in treating cancer is a subject that expresses an MHC encoded by an HLA-A*02:01 allele, an HLA-B*07:02 allele, an HLA-B*35:03 allelle, an HLA-B*18:01 allele, an HLA-B*40:01 allele, an HLA-B*44:02 allele, an HLA-B*40:02 allele, or any combination thereof. In some embodiments, the therapeutic composition comprises: (i) a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, or (ii) a polynucleotide encoding a recombinant polypeptide consisting of at least three cancer-specific CD8+ T cell epitopes, (iii) a vector comprising (i) or (ii), (iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii), or (v) T cells stimulated with APC...

Claims

CLAIMSWHAT IS CLAIMED IS:

1. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising:(i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope;(ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope;(iii) a vector comprising (i) or (ii);(iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or(v) T cells stimulated with APCs comprising (i) or (ii); wherein:(a) the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, KTEVHGRLK, RVSLPKLGYK, or SLFGARPGR;(b) the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is NLRPPTQEL;(c) the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR; and / or(d) the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL.

2. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising:(i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope;(ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope;(iii) a vector comprising (i) or (ii);(iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or(v) T cells stimulated with APCs comprising (i) or (ii); wherein:(a) the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL;(b) the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL;(c) the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL or KPRPDVTNEL;(d) the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL;(e) the subject expresses an MHC encoded by an HLA-B*40:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL;(f) the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL; and / or(g) the subject expresses an MHC encoded by an HLA-B* 18:01 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL.

3. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising:(i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope;(ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope;(iii) a vector comprising (i) or (ii);(iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or(v) T cells stimulated with APCs comprising (i) or (ii); wherein:(a) the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK or RVFTSSLKTK;(b) the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is RPASPRPAP; and / or(c) the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM.

4. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising:(i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or(ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope,(iii) a vector comprising (i) or (ii);(iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or-Tll-(v) T cells stimulated with APCs comprising (i) or (ii); wherein:(a) the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL;(b) the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, or KTEVHGRLK;(c) the subject expresses an MHC encoded by an HLA-A*31 :01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR;(d) the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, RPASPRPAP, NLRPPTQEL, or KPRPDVTNEL;(e) the subject expresses an MHC encoded by an HLA-B*35:03 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, RPASPRPAP, NLRPPTQEL, or KPRPDVTNEL;(f) the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL;(g) the subject expresses an MHC encoded by an HLA-B*40:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL;(h) the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL or KEFAFLEHSL;(i) the subject expresses an MHC encoded by an HLA-B* 18:01 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL; and / or(j) the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL, NLRPPTQEL or KPRPDVTNEL.

5. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising:(i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, or(ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope,(iii) a vector comprising (i) or (ii);(iv) antigen presenting cells (APCs) comprising (i), (ii), or (iii); or(v) T cells stimulated with APCs comprising (i) or (ii);wherein:(a) the subject expresses an MHC encoded by an HLA-A* 15:01 allele and the cancer-specific CD8+ T cell epitope is GQHLHLETF;(b) the subject expresses an MHC encoded by an HLA-C*03:04 allele and the cancer-specific CD8+ T cell epitope is IATKIALQM;(c) the subject expresses an MHC encoded by an HLA-C*07:02 allele and the cancer-specific CD8+ T cell epitope is LRPPTQEL, NLRPPTQEL or KPRPDVTNEL;(d) the subject expresses an MHC encoded by an HLA-A*03:01 allele and the cancer-specific CD8+ T cell epitope is LKPDHIQR, RVSLPKLGYK, SLFGARPGR, KTEVHGRLK, RLHSFTLRQK, RVFTSSLKTK, RVLAKGLAK, KTPLHTLLK, KSYSKVLVR, MTYKIHFKK or SLYQTIRLK;(e) the subject expresses an MHC encoded by an HLA-B*07:02 allele and the cancer-specific CD8+ T cell epitope is SPSSASLAL, KPRPDVTNEL, NLRPPTQEL, RPASPRPAP, GPRPSPTRSV, SPRSPSPSL, VPQEAVRAPL, VPASPALSR, SPSARPPSL, SPTLNVSAL, or SPSSASLTL;(f) the subject expresses an MHC encoded by an HLA-B*08:01 allele and the cancer-specific CD8+ T cell epitope is LNKVKTSL or NLKTEILRL;(g) the subject expresses an MHC encoded by an HLA-C*07:01 allele and the cancer-specific CD8+ T cell epitope is FRGVFVHRY;(h) the subject expresses an MHC encoded by an HLA-B*35:01 allele and the cancer-specific CD8+ T cell epitope is TSGPVTEKY;(i) the subject expresses an MHC encoded by an HLA-A*02:05 allele and the cancer-specific CD8+ T cell epitope is VVAAHLAGA;(j) the subject expresses an MHC encoded by an HLA-A*02:01 allele and the cancer-specific CD8+ T cell epitope is GVYDGREHTV or KLVELEHTL;(k) the subject expresses an MHC encoded by an HLA-B*40:01 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL;(l) the subject expresses an MHC encoded by an HLA-B*44:02 allele and the cancer-specific CD8+ T cell epitope is KEFAFLEHSL or HELGFKVVL;(m) the subject expresses an MHC encoded by an HLA-B* 18:01 allele and the cancer-specific CD8+ T cell epitope is HELGFKVVL;(n) the subject expresses an MHC encoded by an HLA-A*31:01 allele and the cancer-specific CD8+ T cell epitope is SLFGARPGR.

6. The method of any one of claims 1-5, wherein the cancer is esophageal cancer.

7. The method of any one of claims 1-6, wherein the polynucleotide is a vector.

8. A composition comprising a vector encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope comprising GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, RVFTSSLKTK or any combination thereof.

9. The composition of claim 8, wherein the recombinant polypeptide comprises a single cancer-specific CD8+ T cell epitope selected from the group consisting of GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, or RPASPRPAP.

10. The composition of claim 8 or 9, wherein the vector encodes a single cancer-specific CD8+ T cell epitope selected from the group consisting of GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, HELGFKVVL, LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, LRPPTQEL, or RPASPRPAP.

11. A composition comprising a vector encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope comprising GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, or HELGFKVVL or any combination thereof.

12. The composition of any of claims 8-11, wherein the recombinant polypeptide comprises a single cancer-specific CD8+ T cell epitope selected from the group consisting of GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, or HELGFKVVL.

13. The composition of any of claims 8-12, wherein the vector encodes a single cancerspecific CD8+ T cell epitope selected from the group consisting of GVYDGREHTV, KLVELEHTL, SPSSASLAL, KPRPDVTNEL, KEFAFLEHSL, or HELGFKVVL.

14. A composition comprising a vector encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope comprising RPASPRPAP, IATKIALQM,SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, or RVFTSSLKTK or any combination thereof.

15. The composition of any of claims 8-10 or 14, wherein the recombinant polypeptide comprises a single cancer-specific CD8+ T cell epitope selected from the group consisting of RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, or RVFTSSLKTK.

16. The composition of any of claims 8-10 or 14-15, wherein the vector encodes a single cancer-specific CD8+ T cell epitope selected from the group consisting of RPASPRPAP, IATKIALQM, SLYQTIRLK, KTPLHTLLK, RLHSFTLRQK, or RVFTSSLKTK.

17. A composition comprising a vector encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope comprising LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, or LRPPTQEL or any combination thereof.

18. The composition of any of claims 8-10 or 17, wherein the recombinant polypeptide comprises a single cancer-specific CD8+ T cell epitope selected from the group consisting of LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, or LRPPTQEL.

19. The composition of any of claims 8-10 or 17-18, wherein the vector encodes a single cancer-specific CD8+ T cell epitope selected from the group consisting of LKPDHIQR, SLFGARPGR, KTEVHGRLK, NLRPPTQEL, RVSLPKLGYK, or LRPPTQEL.

20. A composition comprising a vector encoding a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope comprising RPASPRPAP, GQHLHLETF, IATKIALQM, SLYQTIRLK, GPRPSPTRSV, KTPLHTLLK, RLHSFTLRQK, VPQEAVRAPL, LNKVKTSL, NLKTHLRL, RVFTSSLKTK, RVLAKGLAK, FRGVFVHRY, SPSSASLTL, TSGPVTEKY, VVAAHLAGA, KSYSKVLVR, MTYKIFIFKK, VPASPALSR, SPSARPPSL, SPTLNVSAL, or any combination thereof.

21. The composition of claim 20, wherein the recombinant polypeptide comprises a single cancer-specific CD8+ T cell epitope selected from the group consisting of RPASPRPAP, GQHLHLETF, IATKIALQM, SLYQTIRLK, GPRPSPTRSV, KTPLHTLLK, RLHSFTLRQK, VPQEAVRAPL, LNKVKTSL, NLKTHLRL, RVFTSSLKTK, RVLAKGLAK, FRGVFVHRY, SPSSASLTL, TSGPVTEKY, VVAAHLAGA.

22. The composition of claim 20 or 21, wherein the vector encodes a single cancer-specific CD8+ T cell epitope selected from the group consisting of RPASPRPAP, GQHLHLETF, IATKIALQM, SLYQTIRLK, GPRPSPTRSV, KTPLHTLLK, RLHSFTLRQK,VPQEAVRAPL, LNKVKTSL, NLKTHLRL, RVFTSSLKTK, RVLAKGLAK, FRGVFVHRY, SPSSASLTL, TSGPVTEKY, VVAAHLAGA.

23. The method of any one of claims 1-7 or the composition of any one of claims 8-22, wherein the cancer-specific CD8+ T cell epitope is an esophageal cancer-specific CD8+ T cell epitope.

24. The method of any one of claims 1-7 or the composition of any one of claims 8-22, wherein the vector is a vector selected from a plasmid, a cosmid, a bacterial vector, a viral vector, an artificial chromosome, a liposome, a lipid nanoparticle, or an exosome.

25. The method or composition of claim 24 wherein the vector is a viral vector.

26. The method or composition of claim 24 or 25, wherein the viral vector is an adenovirus vector.

27. The method or composition of claim 26, wherein the adenovirus vector is an Ad5 vector.

28. The method or composition of claim 24 or 25, wherein the viral vector is an AAV.

29. The method of any one of claims 1-7 and 23-28, or the composition of any one of claims8-28, wherein the recombinant polypeptide is from 8 to 100 amino acids in length.

30. The method of any one of claims 1-7 and 23-29, or the composition of any one of claims 8-29, wherein the cancer-specific CD8+ T cell epitope binds to a MHC class I molecule with a binding affinity of 500 nM or less.

31. The method of any one of claims 1-7 and 23-29, or the composition of any one of claims 8-29, wherein the cancer-specific CD8+ T cell epitope binds to a MHC class I molecule with a rank score of 2% or less.

32. The method of any one of claims 1-7 and 23-31, or the composition of any one of claims 8-31, wherein the recombinant polypeptide comprises a single cancer-specific CD8+ T cell epitope.

33. The method of any one of claims 1-7 and 23-32, or the composition of any one of claims 8-32 wherein the vector encodes a single cancer-specific CD8+ T cell epitope.

34. The method of any one of claims 1-7 and 23-33, or the composition of any one of claims 8, 11, 14, 17, 20, and 23-33, wherein the recombinant polypeptide comprises at least two different cancer-specific CD8+ T cell epitopes.

35. The method of any one of claims 1-7 and 23-33, or the composition of any one of claims 8, 11, 14, 17, 20, and 23-33, wherein the vector comprises at least two different recombinant polypeptides, each comprising a cancer-specific CD8+ T cell epitope.

36. The method of any one of claims 1-7 and 23-35, or the composition of any one of claims 8-35, wherein the composition further comprises an adjuvant.

37. The method of any one of claims 1-7 and 23-36, wherein the method further comprises administering a second therapeutic agent.

38. The method of claim 37, wherein the second therapeutic agent is selected from an immune checkpoint inhibitor, a chemotherapeutic agent, a small molecule inhibitor, or radiotherapy.

39. The method of any one of claims 1-7 and 23-38, wherein the polynucleotide encoding the recombinant polypeptide is DNA.

40. The method of any one of claims 1-7 and 23-38, wherein the polynucleotide encoding the recombinant polypeptide is RNA.

41. The method of any one of claims 1-7, 23-28, and 39, wherein the polynucleotide encoding the recombinant polypeptide is messenger RNA (mRNA).

42. The method of any one of claims 1-7 and 23-41, or the composition of any one of claims 8-36, wherein the recombinant polypeptide is from 8 to 12 amino acids in length.

43. The method of any one of claims 1-7 and 23-42, or the composition of any one of claims 8-36 and 42, wherein the polynucleotide encoding the recombinant polypeptide is from 9 to 10 amino acids in length.

44. The method of any one of claims 1-7 and 23-43, or the composition of any one of claims 8-36 and 42-43, wherein the polynucleotide encoding the recombinant polypeptide is 9 amino acids in length.

45. The method of any one of claims 1-7 and 23-44, or the composition of any one of claims 8-36 and 42-44, wherein the polynucleotide encoding the recombinant polypeptide is 10 amino acids in length.

46. The composition of any one of claims 8-36 and 42-45, for use in treating cancer.

47. The composition of claim 46, wherein the cancer is selected from a colorectal cancer, prostate cancer, esophageal cancer, liver cancer, renal cancer, lung cancer, bladder cancer, breast cancer, pancreatic cancer, brain cancer, hepatocellular cancer, lymphoma, leukaemia, gastric cancer, cervical cancer, ovarian cancer, thyroid cancer, melanoma, carcinoma, head and neck cancer, skin cancer, nasopharyngeal cancer, Epstein Barr driven cancers, Human Papilloma virus driven cancers and soft tissue sarcoma.

48. The composition of claim 45 or 46, wherein the cancer is an esophageal cancer.

49. The method or composition of any one of the preceding claims, wherein the composition induces an epitope-specific T cell response when administered to a subject.

50. The method or composition of claim 49, wherein the response is an inflating memory CD8+ T cell response.

51. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ T cells characterised by markers comprising CX3CR1+, KLRG-1+, CD44+, and / or CD62L-.

52. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ T cells characterised by markers comprising CX3CR1+, KLRG-1+, CD44+, CD62L-, CD27-(low), and / or CD127-(low).

53. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD44+ T cells.

54. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD62L- T cells.

55. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD44+ / CD62L- T cells.

56. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ / CD44+ / CD62L- / CD27- / CD127- T cells, CD8+ / CX3CRl+ / KLRG-l+ / CD44+ / CD62L- / CD27(low) / CD127- T cells, CD8+ / CX3CRl+ / KLRG-l+ / CD44+ / CD62L- / CD27- / CD127(low) T cells, or CD8+ / CX3CRl+ / KLRG-l+ / CD44+ / CD62L- / CD27(low) / CD127(low) T cells.

57. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that have sustained expression of Tbx21 and / or E2f2.

58. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that have low expression of Eomes.

59. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that form from 0.01 percent to 20 percent of total circulating CD8+ T cells in the subject.

60. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that maintain a memory effector phenotype for at least 30 days.

61. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of CD8+ / CX3CR1+ / KLRG-1+ T cells that have low expression of PD-1, Tim-3, and / or Lag-3.

62. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of an inflating memory CD8+ T cell response that is capable of controlling tumour growth in the subject greater than 50 days after the composition is administered.

63. The method or composition of any one of the preceding claims, wherein the composition is capable of inducing production of nucleotide sequence encoding the cancer specific CD8+ T cell epitope encodes a polypeptide comprising the cancer specific CD8+ T cell epitope, and wherein the polypeptide comprising the cancer specific CD8+ T cell epitope is not processed by antigen presenting cells of the subject when administered; and wherein when a pharmaceutical composition comprising a corresponding viral vector comprising a nucleotide sequence encoding the cancer specific CD8+ T cell epitope that encodes a polypeptide comprising the cancer specific CD8+ T cell epitope that is processed by antigen presenting cells of the subject when administered, the inflating memory CD8+ T cell response is not induced in the subject.

64. The method or composition of any one of the preceding claims, wherein the cancerspecific CD8+ T cell epitope is a viral antigen, a tumour associated antigen that is overexpressed in a cancer cell, or an antigen that is mutated in a cancer cell.

65. The method or composition of any one of the preceding claims, wherein the cancerspecific CD8+ T cell epitopewherein the polypeptide comprising the cancer specific CD8+ T cell epitope is not processed by the proteasome or immunoproteasome in antigen presenting cells.

66. The method or composition of any one of the preceding claims, wherein the viral vector comprises a CMV promoter and a TATA box.

67. The method or composition of any one of the preceding claims, wherein the viral vector is a replication-deficient AdHu5 adenoviral vector.

68. The method or composition of any one of the preceding claims, wherein the viral vector lacks a sequence encoding the El and E3 proteins.

69. he method or composition of any one of the preceding claims, wherein the viral vector is an AAV.

70. The method or composition of any one of the preceding claims, wherein the composition comprises at least two viral vectors, wherein each of the at least two viral vectors is a viral vector, and wherein each of the at least two viral vectors encode a different single cancer specific CD8+ T cell epitope.

71. The method or composition of any one of the preceding claims, wherein the composition comprises at least three viral vectors, wherein each of the at least three viral vectors is a viral vector, and wherein each of the at least three viral vectors encode a different single cancer specific CD8+ T cell epitope.

72. The method or composition of any one of the preceding claims, wherein the composition comprises at least four viral vectors, wherein each of the at least four viral vectors is a viral vector, and wherein each of the at least four viral vectors encode a different single cancer specific CD8+ T cell epitope.

73. The method or composition of any one of the preceding claims, wherein the composition comprises at least five viral vectors, wherein each of the at least five viral vectors is a viral vector, and wherein each of the at least five viral vectors encode a different single cancer specific CD8+ T cell epitope.

74. The method or composition of any one of the preceding claims, wherein the composition comprises at least six viral vectors, wherein each of the at least six viral vectors is a viral vector, and wherein each of the at least six viral vectors encode a different single cancer specific CD8+ T cell epitope.

75. A pharmaceutical composition comprising the composition of any one of the preceding claims, and a pharmaceutically acceptable carrier, diluent, excipient, or adjuvant.

76. A method of treating or preventing a cancer comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 75 to a subject in need thereof.

77. A method of inducing an inflating memory CD8+ T cell response comprising administering a therapeutically effective amount of the pharmaceutical composition of claim 75 to a subject in need thereof, wherein the inflating memory CD8+ T cell response comprises production of CD8+ / CX3CR1+ / KLRG-1+ T cells.

78. The method or composition of any one of the preceding claims, wherein the vector or composition is administered intravenously or intramuscularly.

79. The method or composition of any one of the preceding claims, wherein the composition is administered as a single dose.

80. The method or composition of any one of the preceding claims, wherein the composition is administered as multiple doses.

81. The method or composition of any one of the preceding claims, wherein the composition is administered in two doses.

82. The method or composition of claim 80 or 81, wherein the first dose is a prime dose.

83. The method or composition of any of claims 80-82, wherein the first dose elicits a measurable immune response in a subject as compared to the immune response in the subject in the absence of administration of the first dose.

84. The method or composition of any one of claims 80-83, wherein the second dose is a booster dose.

85. The method or composition of any one of claims 80-84, wherein the second dose elicits a measurable immune response in a subject as compared to the immune response in the subject in the absence of administration of the second dose.

86. The method or composition of any one of claims 80-85, wherein the second dose is administered 24 weeks after the first dose.

87. The method or composition of any one of claims 80-86, wherein the second dose elicit an immune response that is at least 2 fold greater than the immune response elicited by the first dose.

88. The method or composition of any one of the preceding claims, wherein the composition is administered prophylactically to the subject.

89. The method or composition of any one of the preceding claims, wherein the composition is administered in combination with a second therapeutic agent.

90. The method or composition of any one of the preceding claims, wherein the second therapeutic agent is selected from an immune checkpoint inhibitor, a chemotherapeutic agent, a small molecule inhibitor, or radiotherapy.

91. The method or composition of claim 90, wherein the immune check point inhibitor is an inhibitor of an immune checkpoint protein selected from the group consisting of CTLA-4, PD-1, PD-L1, PD-L2, TIM3, LAG -3, B7-H3, B7-H4, B7-H6, A2aR, BTLA, GALS and IDO.

92. A method of producing the composition of any one of the preceding claims comprising(i) synthesising a nucleotide sequence encoding the single cancer specific CD8+ T cell epitope, as a sense and antisense primer,(ii) cloning the nucleotide sequence encoding the single cancer specific CD8+ T cell epitope synthesized in (i) into a first plasmid,(iii) cloning a sequence comprising the nucleotide sequence encoding the single cancer specific CD8+ T cell epitope from the first plasmid of (ii) into a second vector comprising adenoviral DNA.

93. A method of treating or preventing a cancer comprising administering a composition of any one of the preceding claims to a subject in need thereof, comprising at least two viralvectors are present in the pharmaceutical composition thereby treating the cancer in the subject.

94. The method or composition of any one of the preceding claims, wherein the viral vector comprises a sequence with at least 90% sequence identity to SEQ ID NO: 44 and a sequence with at least 90% sequence identity to SEQ ID NO: 45.

95. The method or composition of any one of the preceding claims, wherein the viral vector further comprises a sequence with at least 90% sequence identity to SEQ ID NO: 47 and a sequence with at least 90% sequence identity to SEQ ID NO: 48.

96. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising:(i) a recombinant polypeptide comprising a cancer-specific CD8+ T cell epitope, wherein the recombinant polypeptide binds to a TCR(ii) a polynucleotide encoding a recombinant polypeptide comprising a cancerspecific CD8+ T cell epitope wherein the recombinant polypeptide encoded by the polynucleotide binds to a TCR;(iii) a cell comprising a recombinant polypeptide or a polynucleotide of (i) or (ii);(iv) a recombinant polypeptide comprising an antigen binding domain wherein the antigen binding domain binds to a cancer-specific CD8+ T cell epitope;(v) a polynucleotide encoding a recombinant polypeptide comprising an antigen binding domain wherein the antigen binding domain binds to a cancer-specific CD8+ T cell epitope; or(vi) a cell comprising a recombinant polypeptide or a polynucleotide of (iii) or (iv).

97. The viral vector according to any of the preceding claims, wherein the viral vector comprises one or more of a promoter, a translation initiating sequence, a start codon, a T cell epitope codon, a stop codon, a polyadenylation sequence, wherein(i) the promoter is selected from a CMV promoter, an RSV promoter, and an EFla promoter, optionally wherein the promoter comprises a sequence as set forth in SEQ ID NO: 36;(ii) the translation initiation sequence comprises a sequence as set forth in SEQ ID NO: 37; and the polyadenylation sequence comprises a sequence as set forth in SEQ ID NO: 43.

98. The viral vector according to any of the preceding claims, wherein the vector comprises a deletion or a functional deletion in the El gene at an El gene locus.

99. The viral vector of claim 98, wherein the vector comprises a transgene insertion at the El gene locus.

100. The method of claim 2, wherein the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence GVYDGREHTV, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KLVELEHTL; wherein the subject expresses an MHC encoded by an HLA- A*02:01 allele.

101. The method of claim 2, wherein the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL; wherein the subject expresses an MHC encoded by an HLA- B*07:02 allele.

102. The method of claim 2, wherein the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL; wherein the subject expresses an MHC encoded by an HLA- B*35:03 allele.

103. The method of claim 2, wherein the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA- B*40:01 allele.

104. The method of claim 2, wherein the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA- B*40:02 allele.

105. The method of claim 2, wherein the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ Tcell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA- B*44:02 allele.

106. The method of claim 2, wherein the method comprises administering to the subject (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL; wherein the subject expresses an MHC encoded by an HLA- B*18:01 allele.

107. The composition of claim 8, wherein the composition comprises (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence GVYDGREHTV, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KLVELEHTL.

108. The composition of claim 107, for use in treating esophageal cancer in a subject.

109. The composition of claim 107, for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-A*02:01 allele.

110. The composition of claim 8, wherein the composition comprises (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence SPSSASLAL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KPRPDVTNEL.

111. The composition of claim 110, for use in treating esophageal cancer in a subject.

112. The composition of claim 110, for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*07:02 allele.

113. The composition of claim 110, for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*35:03 allele.

114. The composition of claim 8, wherein the composition comprises (i) a first adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence KEFAFLEHSL, and (ii) a second adenoviral vector comprising a sequence encoding a single cancer-specific CD8+ T cell epitope having the sequence HELGFKVVL.

115. The composition of claim 114, for use in treating esophageal cancer in a subject.

116. The composition of claim 114, for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*40:01 allele.

117. The composition of claim 114, for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*40:02 allele.

118. The composition of claim 114, for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B*44:02 allele.

119. The composition of claim 114, for use in treating esophageal cancer in a subject, wherein the subject expresses an MHC encoded by an HLA-B* 18:01 allele.

120. The method of any one of claims 100-106 or the composition of any one of claims 107- 119, wherein the first adenoviral vector is and Ad5 adenoviral vector and / or the second adenoviral vector is and Ad5 adenoviral vector.

121. The method of any one of claims 100-106 and 120 or the composition of any one of claims 107-120, wherein the first adenoviral vector comprises a deletion or a functional deletion in the El gene at an El gene locus and / or the second adenoviral vector comprises a deletion or a functional deletion in the El gene at an El gene locus.

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