NEOANTIGENS AND METHODS OF THEIR USE

1 - 294 . (canceled)

295 . A method of treating cancer in a subject in need thereof comprising administering to the subject a pharmaceutical composition comprising:

(i) a recombinant or synthetic HLA-matched neoantigenic peptide or a polynucleotide encoding the recombinant neoantigenic peptide; and

(ii) a pharmaceutically acceptable excipient;

wherein the neoantigenic peptide comprises a tumor-specific neoepitope comprising one or more contiguous mutant amino acids encoded by a frameshift, wherein the tumor-specific neoepitope is encoded by a gene of cancer cells of the subject or expressed by cancer cells of the subject and is not expressed by a gene of non-cancer cells of the subject or is not encoded by a gene of the non-cancer cells, wherein the tumor-specific neoepitope comprises an amino acid sequence represented by:

A x B y C z ,

wherein:

x is 0 or at least 1 and each A is an amino acid encoded by the gene of the cancer cells of the subject and the gene of the non-cancer cells of the subject;

B y is absent;

z is at least 1 and each C represents the one or more contiguous mutant amino acids encoded by the frameshift;

x+y+z is at least 8;

and

the gene encoding the tumor-specific neoepitope is a gene selected from the group consisting of:

(a) APC, wherein C z comprises one or more contiguous amino acids of

(i)

AKFQQCHSTLEPNPADCRVLVYLQNQPGTKLLNFLQERNLPPKVVLRH

PKVHLNTMFRRPHSCLADVLLSVHLIVLRVVRLPAPFRVNHAVEW,

(ii)

APVIFQIALDKPCHQAEVKHLHHLLKQLKPSEKYLKIKHLLLKRERVDL

SKLQ,

or

(iii)

MLQFRGSRFFQMLILYYILPRKVLQMDFLVHPA;

(b) β2M, wherein C z comprises one or more contiguous amino acids of

(i)

RMERELKKWSIQTCLSARTGLSISCTTLNSPPLKKMSMPAV,

or

(ii

LCSRYSLFLAWRLSSVLQRFRFTHVIQQRMESQIS;

(c) GATA3, wherein Cz comprises one or more contiguous amino acids of

(i)

PGRPLQTHVLPEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHR

HGLEPCSMLTGPPARVPAVPFDLHFCRSSIMKPKRDGYMFLKAESKIMF

ATLQRSSLWCLCSNH;

or

(ii)

PRPRRCTRHPACPLDHTTPPAWSPPWVRALLDAHRAPSESPCSPFRLAFL

QEQYHEA;

(d) TP53, wherein Cz comprises one or more contiguous amino acids of

(i)

SSQNARGCSPRGPCTSSSYTGGPCTSPLLAPVIFCPFPENLPGQLRFPS

GLLAFWDSQVCDLHVLPCPQQDVLPTGQDLPCAAVG,

(ii)

GAAPTMSAAQIAMVWPLLSILSEWKEICVWSIWMTETLFDIVWWCPMS

RLRLALTVPPSTTTTCVTVPAWAA,

(iii)

TGGPSSPSSHWKTPVVIYWDGTALRCVFVPVLGETGAQRKRISARKGSL

TTSCPQGALSEHCPTTPAPLPSQRRNHWMENISPFRSVGVSASRCSES,

(iv)

FHTPARHPRPRHGHLQAVTAHDGGCEALPPP,

(v)

CCPRTILNNGSLKTQVQMKLPECQRLLPPWPLHQQLLHRRPLHQPPPGP

CHLLSLPRKPTRAATVSVWASCILGQPSL,

(vi)

VRKHFQTYGNYFLKTTFCPPCRPKQWMI,

or

(vii)

LARTPLPSTRCFANWPRPALCSCGLIPHPRPAPASAPWPSTSSHST;

or,

(e) VHL wherein C z comprises one or more contiguous amino acids of

(i)

ELQETGHRQVALRRSGRPPKCAERPGAADTGAHCTSTDGRLKISVETYT

VSSQLLMVLMSLDLDTGLVPSLVSKCLILRVK,

(ii)

KSDASRLSGA,

(iii)

RTAYFCQYHTASVYSERAMPPGCPEPSQA,

(iv)

TRASPPRSSSAIAVRASCCPYGSTSTASRSPTQRCRLARAAASTATEVTF

GSSEMQGHTMGFWLTKLNYLCHLSMLTDSLFLPISHCQCIL,

(v)

SSLRITGDWTSSGRSTKIWKTTQMCRKTWSG,

or

(vi)

RRRRGGVGRRGVRPGRVRPGGTGRRGGDGGRAAAARAALGELARALP

GHLLQSQSARRAARMAQLRRRAAALPNAAAWHGPPHPQLPRSPLALQ

RCRDTRWASG;

and

wherein the neoantigenic peptide is from 8 to 100 amino acids in length.

296 . The method of claim 295 , wherein the gene encoding the tumor-specific neoepitope is GATA3, wherein C z comprises one or more contiguous amino acids of

PRPRRCTRHPACPLDHTTPPAWSPPWVRALLDAHRAPSESPCSPFRLAF

LQEQYHEA.

297 . The method of claim 295 , wherein Cz comprises one or more contiguous amino acids of

PGRPLQTHVLPEPHLALQPLQPHADHAHADAPAIQPVLWTTPPLQHGHR

HGLEP CSMLTGPPARVPAVPFDLHFCRSSIMKPKRDGYMFLKAESKIM

FATLQRSSLWCLCSNH.

298 . (canceled)

299 . The method of claim 295 , wherein the tumor-specific neoepitope binds to a MHC class I molecule with a binding affinity of 500 nM or less.

300 . The method of claim 295 , wherein the pharmaceutical composition comprises at least two different neoantigenic peptides, wherein the gene encoding the tumor-specific neoepitope of each of the at least two different neoantigenic peptides is GATA3.

301 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of HVLPEPHLAL (SEQ ID NO: 1428), RPLQTHVLPE (SEQ ID NO: 1429), or VLWTTPPLQH (SEQ ID NO: 1430).

302 . The method of claim 301 , wherein the tumor-specific neoepitope has a sequence of VLWTTPPLQH (SEQ ID NO: 1430) and the subject express an MHC molecule encoded by a A03:01 HLA allele.

303 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of EPHLALQPL (SEQ ID NO: 529) and the subject express an MHC molecule encoded by a B07:02 or B08:01 HLA allele.

304 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of FLKAESKIMF (SEQ ID NO: 536) and the subject express an MHC molecule encoded by a B08:01 HLA allele.

305 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of IMKPKRDGYM (SEQ ID NO: 550) and the subject express an MHC molecule encoded by a B08:01 HLA allele.

306 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of LHFCRSSIM (SEQ ID NO: 556) and the subject express an MHC molecule encoded by a B08:01 HLA allele.

307 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of MFATLQRSSL (SEQ ID NO: 567) and the subject express an MHC molecule encoded by a B07:02 or B08:01 HLA allele.

308 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of MFLKAESKI (SEQ ID NO: 568) and the subject express an MHC molecule encoded by a A24:02 HLA allele.

309 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of VLPEPHLAL (SEQ ID NO: 594) and the subject express an MHC molecule encoded by a A02.01 HLA allele.

310 . The method of claim 297 , wherein the tumor-specific neoepitope has a sequence of YMFLKAESKI (SEQ ID NO: 598) and the subject express an MHC molecule encoded by a A24:02 or HLA allele.

311 . The method of claim 296 , wherein the tumor-specific neoepitope has a sequence of APSESPCSPF (SEQ ID NO: 1431), CPLDHTTPPA (SEQ ID NO: 1432), FLQEQYHEA (SEQ ID NO: 1433), RLAFLQEQYH (SEQ ID NO: 1434), SPCSPFRLAF (SEQ ID NO: 1435) or SPPWVRALL (SEQ ID NO: 1436).

312 . The method of claim 295 , wherein the cancer is breast cancer.

313 . The method of claim 312 , wherein the breast cancer is selected from the group consisting of metastatic breast cancer, breast invasive carcinoma, luminal NS carcinoma of breast, HER-2-positive breast cancer and MSI+ breast cancer.

314 . The method of claim 295 , wherein the pharmaceutical composition further comprises an adjuvant.

315 . The method of claim 295 , wherein the method further comprises administering an immune checkpoint inhibitor.