Target peptides for immunotherapy and diagnostics
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) at least one synthetic target peptide, wherein each synthetic target peptide:
(i) is between 8 and 50 amino acids long, and
(ii) comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 2164-2167 and 2374; and
(b) a therapeutically effective amount of an adjuvant.
2. The composition of claim 1 , wherein at least one serine residue in at least one of the synthetic target peptides is replaced with a homo-serine.
3. The composition of claim 1 , wherein the composition comprises at least 5 different peptides.
4. The composition of claim 1 , further comprising at least one peptide derived from MelanA (MART-I), gp100 (Pmel 17), tyrosinase, TRP-1, TRP-2, MAGE-1, MAGE-3, BAGE, GAGE-1, 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, p185erbB2, p180erbB-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, β-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.
5. The composition of claim 1 , futher comprising an agent selected from the groupconsisting of anti-CTLA-4, vermurafenib, ipilimumab, dacarbazine, IL-2, temozolomide, imatinib, gefitinib, erlotinib, sunitinib, tyrphostins and telatinib.
6. The composition of claim 1 , further comprising darcarbazine, carmustine and tamoxifen.
7. The composition of claim 1 , wherein at least one of the synthetic target peptides is O-GlcNAcylated.
8. The composition of claim 1 , wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2164, wherein the serine at the fourth position in the sequence is O-GlcNAcylated.
9. The composition of claim 1 , wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2165, wherein the threonine at the fifth position in the sequence is O-GlcNAcylated.
10. The composition of claim 1 , wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2166, wherein the arginine at the first position in the sequence is mono-methylated and the threonine at the fifth position in the sequence is O-GlcNAcylated.
11. The composition of claim 1 , wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2167, wherein the arginine at the first position in the sequence is di-methylated and the threonine at the fifth position in the sequence is O-GlcNAcylated.
12. The composition of claim 1 , wherein at least one of the synthetic target peptides comprises the amino acid sequence set forth in SEQ ID NO: 2374, wherein the serine at the fourth position in the sequence is O-GlcNAcylated.
13. The composition of claim 1 , wherein composition has the ability to stimulate a T cell mediated immune response to at least one of the synthetic target peptides.
14. The composition of claim 1 , 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).
15. A composition comprising a synthetic target peptide and an adjuvant, wherein the synthetic target peptide is between 8 and 50 amino acids long and comprises the amino acid sequence set forth in SEQ ID NO: 2165.
16. The composition of claim 15 , wherein the threonine at the fifth position of SEQ ID NO: 2165 is O-GlcNAcylated.
17. The composition of claim 15 , wherein the adjuvant is QS-21.
18. The composition of claim 16 , wherein the adjuvant is QS-21.