Neoantigens and methods of their use

A composition comprising:

• a. a recombinant or synthetic HLA-matched neoantigenic peptide,
• b. a polynucleotide encoding the recombinant neoantigenic peptide,
• c. antigen presenting cells (APCs) comprising (a) or (b),
• d. T cells stimulated with APCs comprising (a) or (b), or
• e. a T cell receptor (TCR) that binds to an MHC:
• peptide complex comprising a tumor-specific neoepitope of the recombinant or synthetic HLA-matched neoantigenic peptide;
• wherein the neoantigenic peptide comprises a tumor-specific neoepitope comprising a mutant amino acid sequence encoded by a sequence downstream of a frameshift mutation in a gene, and wherein:
• i. the gene is selected from the group consisting of GBP3, LMAN1, NDUFC2, SEC31A, SLC35F5, TTK, EPHB2, XPOT, THAP5, and MSH3;
• or
• ii. the gene is TGFBR2 and the frameshift is P129fs+1 or K128fs−1.

A method of treating or preventing a disease or a condition in a human subject in need thereof comprising administering to the human subject a pharmaceutical composition comprising:

• a. a recombinant or synthetic HLA-matched neoantigenic peptide,
• b. a polynucleotide encoding the recombinant neoantigenic peptide,
• c. antigen presenting cells (APCs) comprising (a) or (b),
• d. T cells stimulated with APCs comprising (a) or (b), or
• e. a T cell receptor (TCR) that binds to an MHC:
• peptide complex comprising a tumor-specific neoepitope of the recombinant or synthetic HLA-matched neoantigenic peptide;
• wherein the neoantigenic peptide comprises a tumor-specific neoepitope comprising a mutant amino acid sequence encoded by a sequence downstream of a frameshift mutation in a gene, and wherein:
• i. the gene is FAM111B, and the human subject expresses an MHC encoded by an HLA A03.01 allele;
• or
• ii. the gene is UBR5 and the human subject expresses an MHC encoded by an HLA B07:02 allele.