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 WT1-expressing cancer, comprising heteroclitic peptides derived from the WT-1 protein.
1. A nucleic acid molecule encoding the amino acid sequence NLMNLGATL (SEQ ID NO:6), CMTWNLMNLGATLKG (SEQ ID NO:14), MTWNLMNLGATLKGV (SEQ ID NO:15), TWNLMNLGATLKGVA (SEQ ID NO:16), WNLMNLGATLKGVAA SEQ ID NO:17), or CMTWNLMNLGATLKGVA (SEQ ID NO:22).
2. A vector comprising the nucleic acid molecule of claim 1 .
3. The vector of claim 2 wherein the vector is an attenuated virus vector or a Salmonella typhi vector.
4. The vector of claim 2 further encoding an immunomodulatory compound.
5. A vaccine comprising the vector of claim 4 and an adjuvant, carrier or antigen presenting cell.
6. 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 the vaccine of claim 5 , thereby treating a subject with a WT1-expressing cancer, reducing an incidence of a WT1-expressing cancer or its relapse therein.
7. The method of claim 6 , 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).
8. A method of inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer, the method comprising administering to said subject the vaccine of claim 5 , thereby inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer.
9. The method of claim 8 , 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).
10. The vector of claim 4 wherein the immunomodulatory compound is a cytokine, a cytokine receptor, a chemokine, a complement component, any of interleukins 1 to 15, interferon alpha, beta or gamma, tumour necrosis factor, granulocyte-macrophage colony stimulating factor (GM-CSF), macrophage colony stimulating factor (M-CSF), granulocyte colony stimulating factor (G-CSF), neutrophil activating protein (NAP), macrophage chemoattractant and activating factor (MCAF), RANTES, macrophage inflammatory peptides MIP-Ia and MIP-Ib, OX40, OX40L (gp34), lymphotactin, CD40, CD40L, B7.1, B7.2, TRAP, ICAM-1, 2 or 3, CD28, CTLA-4, a heat stable antigen (HSA) or a chondroitin sulfate-modified MHC invariant chain (Ii-CS).
11. A pharmaceutical composition comprising the nucleic acid of claim 1 or a vector comprising said nucleic acid, and a pharmaceutically acceptable carrier, vehicle or excipient.
12. A vaccine comprising (a) the nucleic acid molecule of claim 1 or a vector comprising said nucleic acid molecule, and (b) an adjuvant or a carrier or antigen presenting cell.
13. The vaccine of claim 12 , 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 ISA 51, or GM-CSF.
14. 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 the vaccine of claim 12 , thereby treating a subject with a WT1-expressing cancer, reducing an incidence of a WT1-expressing cancer or its relapse therein.
15. The method of claim 14 , 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).
16. A method of inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer, the method comprising administering to said subject the vaccine of claim 12 , thereby inducing the formation and proliferation of CTL specific for cells of a WT1-expressing cancer.
17. The method of claim 16 , 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).
18. A composition comprising (a) an antigen-presenting cell and (b) the nucleic acid molecule of claim 1 or a vector comprising said nucleic acid molecule.