Neoantigens and methods of their use

A method of treating cancer in a human subject that has cancer comprising administering to the human subject a pharmaceutical composition comprising:

• (i) a recombinant or synthetic HLA-matched neoantigenic peptide,
• (ii) a polynucleotide encoding the recombinant neoantigenic peptide,
• (iii) antigen presenting cells (APCs) comprising (i) or (ii),
• (iv) T cells stimulated with APCs comprising (i) or (ii), or
• (v) a T cell receptor (TCR) that binds to an MEW:
• peptide complex comprising a tumor-specific neoepitope of the recombinant or synthetic HLA-matched neoantigenic peptide;
• and
• a pharmaceutically acceptable excipient;
• 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 GATA3 gene, wherein the tumor-specific neoepitope is (a) encoded by a GATA3 gene of cancer cells of the human subject, (b) expressed by the cancer cells of the human subject, (c) is not expressed by a gene of non-cancer cells of the human subject, and (d) is not encoded by a GATA3 gene of the non-cancer cells;
• and wherein:
• (a) the human subject expresses an MHC encoded by an HLA B08:01 allele and the tumor-specific neoepitope is LHFCRSSIM (SEQ ID NO:
• 556);
• (b) the human subject expresses an MHC encoded by an HLA B08:01 allele or an HLA B07:02 allele and the tumor-specific neoepitope is EPHLALQPL (SEQ ID NO:
• 529);
• (c) the human subject expresses an MHC encoded by an HLA A02:01 allele and the tumor-specific neoepitope is VLPEPHLAL (SEQ ID NO:
• 594);
• and/or
• (d) the human subject expresses an MHC encoded by an HLA A03:01 allele and the tumor-specific neoepitope is VLWTTPPLQH (SEQ ID NO:
• 1430).

A method of making a pharmaceutical composition comprising:

• (i) a recombinant or synthetic HLA-matched neoantigenic peptide,
• (ii) a polynucleotide encoding the recombinant neoantigenic peptide,
• (iii) antigen presenting cells (APCs) comprising (i) or (ii),
• (iv) T cells stimulated with APCs comprising (i) or (ii), or
• (v) 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;
• and
• a pharmaceutically acceptable excipient;
• the method comprising:
• (A) selecting a 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 GATA3 gene, wherein the tumor-specific neoepitope is (a) encoded by a GATA3 gene of cancer cells of the human subject, (b) expressed by the cancer cells of the human subject, (c) is not expressed by a gene of non-cancer cells of the human subject, and (d) is not encoded by a GATA3 gene of the non-cancer cells;
• and
• (B) preparing a pharmaceutical formulation for each of the following,
• wherein:
• (a) the human subject expresses an MHC encoded by an HLA B08:01 allele and the tumor-specific neoepitope is LHFCRSSIM (SEQ ID NO:
• 556);
• (b) the human subject expresses an MHC encoded by an HLA B08:01 allele or an HLA B07:02 allele and the tumor-specific neoepitope is EPHLALQPL (SEQ ID NO:
• 529);
• (c) the human subject expresses an MHC encoded by an HLA A02:01 allele and the tumor-specific neoepitope is VLPEPHLAL (SEQ ID NO:
• 594);
• and/or
• (d) the human subject expresses an MHC encoded by an HLA A03:01 allele and the tumor-specific neoepitope is VLWTTPPLQH (SEQ ID NO:
• 1430).