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 of an 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), WNQMNLGATLK (SEQ ID NO:173), PGCLQQPEQQG (SEQ ID NO:149), LDFAPPGASAY (SEQ ID NO:156), PLPHFPPSL (SEQ ID NO:144), HFPPSLPPT (SEQ ID NO:145), LLAAILDFL (SEQ ID NO:184), ALRNPTACPL (SEQ ID NO:191), GGCALPVSGA (SEQ ID NO:153), LGATLKGVAA (SEQ ID NO:176), TLGVAAGS (SEQ ID NO:177), KRPFMCAYPGC (SEQ ID NO:180) LKTHTRTHT (SEQ ID NO:182) and SEQ ID NOS:1-15.
2. 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, 149 and 184.
3. The isolated WT-1 peptide of claim 1 or 2 , wherein said isolated WT-1 peptide can bind to an HLA class I molecule, an HLA class II molecule, or the combination thereof.
4. A pharmaceutical composition comprising one or more peptides of claim 1 or 2 and a pharmaceutically acceptable carrier, vehicle or excipient.
5. A vaccine comprising (a) one or more isolated WT-1 peptides of claim 1 or 2 and (b) an adjuvant or a carrier.
6. The vaccine of claim 5 , wherein said adjuvant is QS21, Freund's incomplete adjuvant, aluminum phosphate, aluminum hydroxide, BCG, alum, a growth factor, a cytokine, a chemokine, an interleukin, Montanide or GM-CSF.
7. The vaccine of claim 5 further comprising a cell population.
8. The vaccine of claim 7 wherein the cell population is selected from lymphocytes, monocytes, macrophages, dendritic cells, endothelial cells, stem cells or any combination thereof.
9. The vaccine of claim 7 wherein the cell population is autologous, syngeneic or allogeneic.
10. The vaccine of claim 7 wherein the population is obtained from peripheral blood, leukopheresis blood product, apheresis blood product, peripheral lymph nodes, gut associated lymphoid tissue, spleen, thymus, cord blood, mesenteric lymph nodes, liver, a site of immunologic lesions, pancreas, cerebrospinal fluid, a tumor sample, or granulomatous tissue.
11. A composition comprising (a) an antigen-presenting cell and (b) one or more peptides of claim 1 or 2 .
12. The composition of claim 11 wherein the antigen-presenting cell is a dendritic cell, monocyte, macrophage, cytokine-activated monocyte or an EBV-transformed B-lymphoblastoid cell.
13. The composition of claim 11 wherein the antigen-presenting cell is from a cell line.
14. An isolated WT-1 peptide consisting of 16-30 amino acids comprising an amino acid sequence selected from SEQ ID NO:1-15.
15. 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 one or more peptides of any one of claim 1 , 2 or 14 , a composition thereof, a composition thereof further comprising an antigen presenting cell, or a vaccine thereof or any combination thereof, thereby treating a subject with a WT-1-expressing cancer, reducing an incidence of a WT-1-expressing cancer or its relapse therein.
16. The method of claim 15 , 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), mesothelioma or a non-small cell lung cancer (NSCLC).
17. 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 one or more peptides of any one of claim 1 , 2 or 14 , a composition thereof or a vaccine thereof or any combination thereof, thereby inducing the formation and proliferation of CTL specific for cells of a WT-1-expressing cancer.
18. The method of claim 17 , 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), mesothelioma or a non-small cell lung cancer (NSCLC).
19. A method of inducing formation and proliferation of (a) a WT1 protein-specific CD8+ lymphocyte; or (b) a CD4+ lymphocyte specific for the WT1 protein, or the combination thereof, the method comprising administering to a subject one or more peptides of any one of claim 1 , 2 or 14 , a composition thereof, a composition thereof further comprising an antigen presenting cell, or a vaccine thereof, or any combination thereof, thereby inducing formation and proliferation of (a) a WT1 protein-specific CD8+ lymphocyte; or (b) a CD4+ lymphocyte specific for the WT1 protein; or a combination thereof.
20. The method of claim 19 , wherein said WT1-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), mesothelioma or a non-small cell lung cancer (NSCLC).
21. A method of inducing formation and proliferation of WT1 protein-specific cytotoxic T lymphocytes comprising contacting a lymphocyte population in vitro or ex vivo with one or more peptides selected from AILDFLLLQ (SEQ ID NO:147), RQRPHPGAL (SEQ ID NO:142), GALRNPTAC (SEQ ID NO:143), THSPTHPPR (SEQ ID NO:146), PGCLQQPEQQG (SEQ ID NO:149), LDFAPPGASAY (SEQ ID NO:156), PLPHFPPSL (SEQ ID NO:144), HFPPSLPPT (SEQ ID NO:145), LLAAILDFL (SEQ ID NO:184), ALRNPTACPL (SEQ ID NO:191), GGCALPVSGA (SEQ ID NO:153), WNQMNLGATLK (SEQ ID NO:173), LGATLKGVAA (SEQ ID NO:176), TLGVAAGS (SEQ ID NO:177), KRPFMCAYPGC (SEQ ID NO:180), LKTHTRTHT (SEQ ID NO:182), and SEQ ID NOS:1-15; or 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, 149, and 184; or an isolated WT1 peptide consisting of 16-30 amino acids comprising an amino acid sequence selected from SEQ ID NOS:1-15, a composition thereof, a composition thereof further comprising an antigen presenting cell, or a vaccine thereof, or any combination thereof, thereby inducing formation and proliferation of WT1 protein-specific cytotoxic T lymphocytes.
22. The method of claim 21 wherein the peptide is a pool of peptides having SEQ ID NOS:1-141.
23. A method of treating a subject with a WT1-expressing cancer or reducing an incidence of a WT1-expressing cancer, or its relapse, the method comprising administering to said subject WT1 protein-specific cytotoxic T lymphocytes obtained by the method of claim 21 , thereby treating a subject with a WT1-expressing cancer, reducing an incidence of a WT1-expressing cancer or its relapse therein.
24. The method of claim 23 wherein the peptide is a pool of peptides having SEQ ID NOS:1-141.
25. A method of inducing formation and proliferation of (a) a WT1 protein-specific CD8+ lymphocyte; or (b) a CD4+ lymphocyte specific for the WT1 protein, or the combination thereof, the method comprising contacting a lymphocyte population in vitro or ex vivo with one or more peptides selected from AILDFLLLQ (SEQ ID NO:147), RQRPHPGAL (SEQ ID NO:142), GALRNPTAC (SEQ ID NO:143), THSPTHPPR (SEQ ID NO:146), PGCLQQPEQQG (SEQ ID NO:149), LDFAPPGASAY (SEQ ID NO:156), PLPHFPPSL (SEQ ID NO:144), HFPPSLPPT (SEQ ID NO:145), LLAAILDFL (SEQ ID NO:184), ALRNPTACPL (SEQ ID NO:191), GGCALPVSGA (SEQ ID NO:153), WNQMNLGATLK (SEQ ID NO:173), LGATLKGVAA (SEQ ID NO:176), TLGVAAGS (SEQ ID NO:177), KRPFMCAYPGC (SEQ ID NO:180), LKTHTRTHT (SEQ ID NO:182) and SEQ ID NOS:1-15; or an isolated WT1 peptide consisting of 8-30 amino acids comprising an amino acid sequence selected from SEQ ID NO: 142, 143, 144, 145, 146, 147, 149, and 184; or an isolated WT1 peptide consisting of 16-30 amino acids comprising an amino acid sequence selected from SEQ ID NOS:1-15, a composition thereof, a composition thereof further comprising an antigen presenting cell, or a vaccine thereof, or any combination thereof, thereby inducing formation and proliferation of (a) a WT1 protein-specific CD8+ lymphocyte; or (b) a CD4+ lymphocyte specific for the WT 1 protein; or a combination thereof.
26. The method of claim 25 wherein the peptides are a pool of peptides having SEQ ID NOS:1-141.
27. A method of treating a subject with a WT1-expressing cancer, the method comprising administering to said subject WT 1 protein-specific cytotoxic T lymphocytes obtained by the method of claim 25 , thereby treating a subject with a WT1-expressing cancer.
28. The method of any one of claim 21 , 23 or 25 wherein the lymphocyte population is obtained from a donor.
29. The method of any one of claim 21 , 23 or 25 wherein the lymphocyte population is obtained from a human source.
30. The method of claim 21 , 23 or 25 , wherein said WT1-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), mesothelioma or a non-small cell lung cancer (NSCLC).