IMMUNOGENIC WT-1 PEPTIDES AND METHODS OF USE THEREOF
This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT-1-expressing cancer, comprising peptides derived from the WT-1 protein.
1 . An isolated WT-1 peptide consisting ofan amino acid sequence selected from among AILDFLLLQ (SEQ ID NO:147), RQRPHPGAL (SEQ ID NO:142), GALRNPTAC (SEQ ID NO:143), THSPTHPPR (SEQ ID NO:146), ASGSEPQQM (SEQ ID NO:151), WNQMNLGATLK (SEQ ID NO:173), PGCLQQPEQQG (SEQ ID NO:149), and LDFAPPGASAY (SEQ ID NO:156).
2 . An isolated WT-1 peptide consisting ofan amino acid sequence selected from among PLPHFPPSL (SEQ ID NO:144), HFPPSLPPT (SEQ ID NO:145), PGCLQQPEQ (SEQ ID NO:148), KLGAAEASA (SEQ ID NO:150), LLAAILDFL (SEQ ID NO:184), CLQQPEQQGV (SEQ ID NO:185) and ALRNPTACPL (SEQ ID NO:191).
3 . An isolated WT-1 peptide consisting of an amino acid sequence selected from amongRDLNALLPAV (SEQ ID NO:152), GGCALPVSGA (SEQ ID NO:153), GAAQWAPVL (SEQ ID NO:154), LDFAPPGAS (SEQ ID NO:155), SAYGSLGGP (SEQ ID NO:157), PAPPPPPPP (SEQ ID NO:158), ACRYGPFGP (SEQ ID NO:159), SGQARMFPN (SEQ ID NO:160), PSCLESQPA (SEQ ID NO:162), NQGYSTVTF (SEQ ID NO:163), HHAAQFPNH (SEQ ID NO:164), HSFKHEDPM (SEQ ID NO:165), CHTPTDSCT (SEQ ID NO:166), CTGSQALLL (SEQ ID NO:167), TDSCTGSQA (SEQ ID NO:168), RTPYSSDNL (SEQ ID NO:169), NLYQMTSQLE (SEQ ID NO:170), WNQMNLGAT (SEQ ID NO:171), WNQMNLGATLK (SEQ ID NO:173), CMTWNQMNLGATLKG (SEQ ID NO:174), NLGATLKGV (SEQ ID NO:175), LGATLKGVAA (SEQ ID NO:176), TLGVAAGS (SEQ ID NO:177), GYESDNHTT (SEQ ID NO:178), FMCAYPGCNK (SEQ ID NO:179), KRPFMCAYPGC (SEQ ID NO:180), RKFSRSDHL (SEQ ID NO:181), LKTHTTRTHT (SEQ ID NO:182), NMHQRNHTKL (SEQ ID NO:183), QARMFPNAPY (SEQ ID NO:190), ALRNPTACPL (SEQ ID NO:191) and APVLDFAPPGASAYG (SEQ ID NO:193).
4 . An isolated WT-1 peptide consisting ofan amino acid sequence selected from among SEQ ID NO:1-141.
5 . An isolated WT-1 peptide consisting of 8-30 amino acids comprising an amino acid sequence selected from SEQ ID NO: 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 184 and 185.
6 . An isolated WT-1 peptide consisting of 16-30 amino acids comprising an amino acid sequence selected from SEQ ID NO:1-141.
7 . The isolated WT-1 peptide of any one of claims 1 - 6 , wherein said isolated WT-1 peptide binds to an HLA class I molecule, an HLA class II molecule, or the combination thereof.
8 . A pharmaceutical composition comprising a peptide of any one of claims 1 - 6 and a pharmaceutically acceptable carrier, vehicle or excipient.
9 . A vaccine comprising (a) one or more isolated WT-1 peptides of claims 1 - 6 and (b) an adjuvant or a carrier.
10 . The vaccine of claim 9 , wherein said adjuvant is QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, a growth factor, a cytokine, a chemokine, an interleukin, Montanideor GM-CSF.
11 . A method of treating a subject with a WT-1-expressing cancer or reducing an incidence of a WT-1-expressing cancer, or its relapse, the method comprising administering to said subject the vaccine of claim 9 , thereby treating a subject with a WT-1-expressing cancer, reducing an incidence of a WT-1-expressing cancer or its relapse therein.
12 . The method of claim 11 , wherein said WT-1-expressing cancer is a leukemia, a desmoplastic small round cell tumor, a gastric cancer, a colon cancer, a lung cancer, a breast cancer, a germ cell tumor, an ovarian cancer, a uterine cancer, a thyroid cancer, a liver cancer, a renal cancer, a Kaposi's sarcoma, a sarcoma, a hepatocellular carcinoma, a Wilms' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), or a non-small cell lung cancer (NSCLC).
13 . A method of inducing the formation and proliferation of CTL specific for cells of a WT-1-expressing cancer, the method comprising administering to said subject the vaccine of claim 9 , thereby inducing the formation and proliferation of CTL specific for cells of a WT-1-expressing cancer.
14 . The method of claim 13 , wherein said WT-1-expressing cancer is a leukemia, a desmoplastic small round cell tumor, a gastric cancer, a colon cancer, a lung cancer, a breast cancer, a germ cell tumor, an ovarian cancer, a uterine cancer, a thyroid cancer, a liver cancer, a renal cancer, a kaposi's sarcoma, a sarcoma, a hepatocellular carcinoma, a Wilms' tumor, an acute myelogenous leukemia (AML), a myelodysplastic syndrome (MDS), or a non-small cell lung cancer (NSCLC).
15 . A composition comprising (a) an antigen-presenting cell and (b) a peptide of any one of claims 1 - 6 .
16 . The method of any one of claims 11 - 14 wherein the cancer is mesothelioma.