Target peptides for immunotherapy and diagnostics

Abstract

A set of target peptides are presented by HLA A*0101, A*0201, A*0301, B*4402, B*2705, B*1402, and B*0702 on the surface of disease cells. They are envisioned to among other things (a) stimulate an immune response to the proliferative disease, e.g., cancer, (b) to function as immunotherapeutics in adoptive T cell therapy or as a vaccine, (c) facilitate antibody recognition of tumor boundaries in surgical pathology samples, (d) act as biomarkers for early detection and/or diagnosis of the disease, and (e) act as targets in the generation antibody-like molecules which recognize the target-peptide/MHC complex.

1 . A composition comprising a target peptide between 8 and 50 amino acids long, wherein the target peptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NOs: 207, 7, 34, 36, 37, 45, 50, 51, 86, 88, 90, 95, 113, 140, 142, 157-159, 161, 181, 189, 197-199, 202, 204, 208, 212, 214, 215, 219, 220, 224, 227, 229, 234, 236, 243-245, 252-255, 259, 261, 264-266, 273, 277-278, 311, 324, 345, 355, 357, 375, 381, 390, 429-435, 437-439, 441-442, 445-450, 454, 463, 465-473, 479-497, 504, 518, 520-533, 535-537, 539-540, 542-544, 551-564, 566-574, 576-577, 580-581, 583-601, 603-604, 606-612, 614, 616, 620, 622-625, 628, 630-631, 634-636, 638, 641, 643, 645, 648, 650-652, 659-660, 666, 669-671, 674, 676-677, 680-681, 686-687, 690, 696, 699, 702-705, 708, 710-718, 722, 733-736, 738, 740, 743, 746-752, 755, 758-759, 761-762, 765, 768, 770-772, 775, 778, 781, 784, 786-788, 791, 797, 800, 803-804, 808-809, 812, 816, 820, 821, 825, 829, 831, 833, 835-837, 839, 842-843, 845, 848-850, 854-855, 859-860, 862-863, 865, 869-874, 877-881, 886, 926, 946-947, 963-966, 987-989, 1038, 1050, 1055, 1058, 1060, 1063, 1066, 1068-1071, 1073, 1076-1079, 1082, 1087, 1090, 1095, 1098, 1102, 1106, 1112-1113, 1120, 1123, 1128, 1132, 1134, 1135-1145, 1149-1152, 1154, 1158-1159, 1162, 1173, 1177-1178, 1180, 1184, 1189, 1195, 1199, 1204, 1208, 1212, 1216, 1220, 1222, 1224, 1228, 1230, 1233, 1237, 1242, 1245, 1250, 1255, 1259, 1263, 1267, 1269-1273, 1275-1281, 1284, 1287-1288, 1290-1294, 1298-1306, 1308, 1311-1321, 1323-1325, 1327-1329, 1332-1339, 1342-1344, 1346-1368, 1371, 1373-1382, 1386, 1389, 1391-1399, 1403-1412, 1417-1419, 1421, 1423-1428, 1432-1442, 1449-1451, 1453, 1455-1464, 1470, 1483-1488, 1490-1497, 1506-1508, 1512-1515, 1523-1538, 1545-1548, 1556-1559, 1571-1575, 1579-1581, 1585-1587, 1591-1596, 1618, 1640-1642, 1650-1652, 1672-1674, 1681-1683, 1688-1690, 1694-1696, 1724-1726, 1730-1732, 1745-1747, 1754-1757, 1785-1787, 1797-1799, 1806-1809, 1827, 1830, 1833-1835, 1843-1845, 1874-1877, 1887-1891, 1900-1902, 1906-1908, 1925-1931, 1935-1937, 1944-1946, 1972-1974, 1988-1989, 2009-2010, 2020, 2072, 2085-2123, 2126-2143, 2152-2153, 2156, 2159, 2161-2163, 2262, 2281, 2363, and 2364. 
     
     
         2 - 4 . (canceled) 
     
     
         5 . The composition of  claim 1 , wherein at least one serine residue in the target peptide is replaced with a homo-serine. 
     
     
         6 - 11 . (canceled) 
     
     
         12 . The composition of  claim 1 , wherein the composition comprises at least 5 different target peptides. 
     
     
         13 - 21 . (canceled) 
     
     
         22 . The composition of  claim 1 , further comprising at least one peptide derived from MelanA (MART-I), gp100 (PmeI 17), tyrosinase, TRP-1, TRP-2, MAGE-I, MAGE-3, BAGE, GAGE-I, GAGE-2, p15(58), CEA, RAGE, NY-ESO (LAGE), SCP-1, Hom/Mel-40, PRAME, p53, H-Ras, HER-2/neu, BCR-ABL, E2A-PRL, H4-RET, IGH-IGK, MYL-RAR, Epstein Barr virus antigens, EBNA, human papillomavirus (HPV) antigens E6 and E7, TSP-180, MAGE-4, MAGE-5, MAGE-6, pI85erbB2, pI80erbB-3, c-met, nm-23H1, PSA, TAG-72-4, CA 19-9, CA 72-4, CAM 17.1, NuMa, K-ras, β-Catenin, CDK4, Mum-1, p16, TAGE, PSMA, PSCA, CT7, telomerase, 43-9F, 5T4, 791Tgp72, alpha-fetoprotein, 13-HCG, BCA225, BTAA, CA 125, CA 15-3 (CA 27.29\BCAA), CA 195, CA 242, CA-50, CAM43, CD68\KP1, CO-029, FGF-5, G250, Ga733 (EpCAM), HTgp-175, M344, MA-50, MG7-Ag, MOV18, NB/70K, NY-CO-1, RCAS1, SDCCAG16, TA-90 (Mac-2 binding protein\cyclophilin C-associated protein), TAAL6, TAG72, TLP and TPS. 
     
     
         23 . (canceled) 
     
     
         24 . The composition of  claim 1 , further comprising an adjuvant. 
     
     
         25 . The composition of  claim 24 , wherein the adjuvant is selected from the group consisting of montanide ISA-51, QS-21, tetanus helper peptides, GM-CSF, cyclophosamide,  bacillus  Calmette-Guerin (BCG),  corynbacterium parvum , levamisole, azimezone, isoprinisone, dinitrochlorobenezene (DNCB), keyhole limpet hemocyanins (KLH), incomplete Freunds adjuvant, complete Freunds adjuvant, mineral gels, aluminum hydroxide (Alum), lysolecithin, pluronic polyols, polyanions, peptides, oil emulsions, dinitrophenol, and diphtheria toxin (DT). 
     
     
         26 - 27 . (canceled) 
     
     
         28 . An antibody or antibody-like molecule that specifically binds to a complex of an MHC molecule and a target peptide of between 8 and 50 amino acids long, wherein the target peptide comprises an amino acid sequence selected from the group consisting of: SEQ ID NOs: 207, 7, 34, 36, 37, 45, 50, 51, 86, 88, 90, 95, 113, 140, 142, 157-159, 161, 181, 189, 197-199, 202, 204, 208, 212, 214, 215, 219, 220, 224, 227, 229, 234, 236, 243-245, 252-255, 259, 261, 264-266, 273, 277-278, 311, 324, 345, 355, 357, 375, 381, 390, 429-435, 437-439, 441-442, 445-450, 454, 463, 465-473, 479-497, 504, 518, 520-533, 535-537, 539-540, 542-544, 551-564, 566-574, 576-577, 580-581, 583-601, 603-604, 606-612, 614, 616, 620, 622-625, 628, 630-631, 634-636, 638, 641, 643, 645, 648, 650-652, 659-660, 666, 669-671, 674, 676-677, 680-681, 686-687, 690, 696, 699, 702-705, 708, 710-718, 722, 733-736, 738, 740, 743, 746-752, 755, 758-759, 761-762, 765, 768, 770-772, 775, 778, 781, 784, 786-788, 791, 797, 800, 803-804, 808-809, 812, 816, 820, 821, 825, 829, 831, 833, 835-837, 839, 842-843, 845, 848-850, 854-855, 859-860, 862-863, 865, 869-874, 877-881, 886, 926, 946-947, 963-966, 987-989, 1038, 1050, 1055, 1058, 1060, 1063, 1066, 1068-1071, 1073, 1076-1079, 1082, 1087, 1090, 1095, 1098, 1102, 1106, 1112-1113, 1120, 1123, 1128, 1132, 1134, 1135-1145, 1149-1152, 1154, 1158-1159, 1162, 1173, 1177-1178, 1180, 1184, 1189, 1195, 1199, 1204, 1208, 1212, 1216, 1220, 1222, 1224, 1228, 1230, 1233, 1237, 1242, 1245, 1250, 1255, 1259, 1263, 1267, 1269-1273, 1275-1281, 1284, 1287-1288, 1290-1294, 1298-1306, 1308, 1311-1321, 1323-1325, 1327-1329, 1332-1339, 1342-1344, 1346-1368, 1371, 1373-1382, 1386, 1389, 1391-1399, 1403-1412, 1417-1419, 1421, 1423-1428, 1432-1442, 1449-1451, 1453, 1455-1464, 1470, 1483-1488, 1490-1497, 1506-1508, 1512-1515, 1523-1538, 1545-1548, 1556-1559, 1571-1575, 1579-1581, 1585-1587, 1591-1596, 1618, 1640-1642, 1650-1652, 1672-1674, 1681-1683, 1688-1690, 1694-1696, 1724-1726, 1730-1732, 1745-1747, 1754-1757, 1785-1787, 1797-1799, 1806-1809, 1827, 1830, 1833-1835, 1843-1845, 1874-1877, 1887-1891, 1900-1902, 1906-1908, 1925-1931, 1935-1937, 1944-1946, 1972-1974, 1988-1989, 2009-2010, 2020, 2072, 2085-2123, 2126-2143, 2152-2153, 2156, 2159, 2161-2163, 2262, 2281, 2363, and 2364. 
     
     
         29 - 33 . (canceled) 
     
     
         34 . A method of treating or preventing cancer comprising administering to a patient in need thereof a therapeutically effective dose of the composition of  claim 1 . 
     
     
         35 - 51 . (canceled) 
     
     
         52 . The composition of  claim 24 , wherein the target peptide comprises the amino acid sequence of SEQ ID NO: 207. 
     
     
         53 . The composition of  claim 52 , wherein the tyrosine at the fifth position of SEQ ID NO: 207 is phosphorylated. 
     
     
         54 . The composition of  claim 1 , wherein the target peptide comprises the amino acid sequence of SEQ ID NO: 207, wherein the tyrosine at the fifth position of SEQ ID NO: 207 is replaced with a mimetic of phosphotyrosine. 
     
     
         55 . The composition of  claim 54 , wherein the mimetic of phosphotyrosine comprises a phosphorous atom linked to a tyrosine through a carbon atom.