Immunogenic wt-1 peptides and methods of use thereof

Abstract

This invention provides peptides, immunogenic compositions and vaccines comprising same, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising same.

1 .- 41 . (canceled) 
     
     
         42 . A nucleic acid molecule encoding the isolated peptide SGQAYMFPNAPYLPSCLES (SEQ ID No: 41). 
     
     
         43 . A vaccine comprising the nucleic acid molecule of  claim 42 . 
     
     
         44 . A vector comprising the nucleic acid molecule of  claim 42 . 
     
     
         45 .- 48 . (canceled) 
     
     
         49 . The vector of  claim 44 , further encoding an additional WT1 peptide is selected from the group consisting of: LVRHHNMHQRNMTKL (SEQ ID No: 1), RSDELVRHHNMHQRNMTKL (SEQ ID No: 2), NKRYFKLSHLQMHSR (SEQ ID No: 3), YMFPNAPYL (SEQ ID NO: 6), and PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No: 4), or any combination thereof. 
     
     
         50 . A method of inducing formation and proliferation of a cytotoxic T lymphocyte (CTL) specific for a WT1-expressing cell, the method comprising contacting a lymphocyte population with the nucleic acid of  claim 42 , or a vaccine or vector thereof, thereby inducing formation and proliferation of CTL specific for a WT1-expressing cell. 
     
     
         51 . A method of inducing formation and proliferation of both (a) a WT1 protein-specific CD8 +  lymphocyte; and (b) a CD4 +  lymphocyte specific for said WT1 protein, the method comprising contacting a lymphocyte population with the nucleic acid of  claim 42 , or a vaccine or vector thereof, thereby inducing formation and proliferation of both (a) a WT1 protein-specific CD8 +  lymphocyte; and (b) a CD4 +  lymphocyte specific for said WT1 protein. 
     
     
         52 . A method of treating a subject with a WT1-expressing cancer, the method comprising administering to said subject the nucleic acid of  claim 42 , or a vaccine or vector thereof, thereby treating a subject with a WT1-expressing cancer. 
     
     
         53 . The method of  claim 52 , wherein said WT1-expressing cancer is an acute myelogenous leukemia (AML), a malignant mesothelioma, a myelodysplastic syndrome (MDS), a non-small cell lung cancer (NSCLC), a Wilms' tumor, 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, or a hepatocellular carcinoma or a lymphoma. 
     
     
         54 . A method of reducing an incidence of a WT1-expressing cancer, or its relapse, in a subject, the method comprising administering to said subject the nucleic acid of  claim 42 , or a vaccine or vector thereof, thereby reducing an incidence of a WT1-expressing cancer, or its relapse, in a subject. 
     
     
         55 . The method of  claim 54 , wherein said WT1-expressing cancer is an acute myelogenous leukemia (AML), a malignant mesothelioma, a myelodysplastic syndrome (MDS), a non-small cell lung cancer (NSCLC), a Wilms' tumor, 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, or a hepatocellular carcinoma or a lymphoma. 
     
     
         56 .- 73 . (canceled) 
     
     
         74 . A nucleic acid molecule encoding the isolated peptide QAYMFPNAPYLPSCL (SEQ ID No: 42). 
     
     
         75 . A vaccine comprising the nucleic acid molecule of  claim 74 . 
     
     
         76 . A vector comprising the nucleic acid molecule of  claim 74 . 
     
     
         77 . The vector of  claim 76 , further encoding an additional WT1 peptide is selected from the group consisting of: LVRHHNMHQRNMTKL (SEQ ID No: 1), RSDELVRHHNMHQRNMTKL (SEQ ID No: 2), NKRYFKLSHLQMHSR (SEQ ID No: 3), YMFPNAPYL (SEQ ID NO: 6), and PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No: 4), or any combination thereof. 
     
     
         78 . A method of inducing formation and proliferation of a cytotoxic T lymphocyte (CTL) specific for a WT1-expressing cell, the method comprising contacting a lymphocyte population with the nucleic acid of  claim 74 , or a vaccine or vector thereof, thereby inducing formation and proliferation of CTL specific for a WT1-expressing cell. 
     
     
         79 . A method of inducing formation and proliferation of both (a) a WT1 protein-specific CD8 +  lymphocyte; and (b) a CD4 +  lymphocyte specific for said WT1 protein, the method comprising contacting a lymphocyte population with the nucleic acid of  claim 74 , or a vaccine or vector thereof, thereby inducing formation and proliferation of both (a) a WT1 protein-specific CD8 +  lymphocyte; and (b) a CD4 +  lymphocyte specific for said WT1 protein. 
     
     
         80 . A method of treating a subject with a WT1-expressing cancer, the method comprising administering to said subject the nucleic acid of  claim 74 , or a vaccine or vector thereof, thereby treating a subject with a WT1-expressing cancer. 
     
     
         81 . The method of  claim 80 , wherein said WT1-expressing cancer is an acute myelogenous leukemia (AML), a malignant mesothelioma, a myelodysplastic syndrome (MDS), a non-small cell lung cancer (NSCLC), a Wilms' tumor, 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, or a hepatocellular carcinoma or a lymphoma. 
     
     
         82 . A method of reducing an incidence of a WT1-expressing cancer, or its relapse, in a subject, the method comprising administering to said subject the nucleic acid of  claim 74 , or a vaccine or vector thereof, thereby reducing an incidence of a WT1-expressing cancer, or its relapse, in a subject. 
     
     
         83 . The method of  claim 82 , wherein said WT1-expressing cancer is an acute myelogenous leukemia (AML), a malignant mesothelioma, a myelodysplastic syndrome (MDS), a non-small cell lung cancer (NSCLC), a Wilms' tumor, 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, or a hepatocellular carcinoma or a lymphoma. 
     
     
         84 . A pharmaceutical composition comprising the vector of  claim 44 . 
     
     
         85 . The vector of  claim 44 , wherein the vector is an attenuated viral vector or a  Salmonella typhi  vector. 
     
     
         86 . The vector of  claim 44 , further encoding an immunomodulatory compound. 
     
     
         87 . The vector of  claim 86 , wherein the immunomodulatory compound is a cytokine, chemokine, or complement component that enhances expression of immune system accessory or adhesion molecules, their receptors, or a combination thereof. 
     
     
         88 . The vector of  claim 86 , wherein the immunomodulatory compound is any of interleukins 1 to 15, interferons 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, or macrophage inflammatory peptides MIP-1a or MIP-1b. 
     
     
         89 . A vaccine comprising the vector of  claim 44 . 
     
     
         90 . The vaccine of  claim 89  further comprising an adjuvant, carrier or antigen presenting cell. 
     
     
         91 . The vaccine of  claim 90  wherein the 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. 
     
     
         92 . A pharmaceutical composition comprising the vector of  claim 76 . 
     
     
         93 . The vector of  claim 76 , wherein the vector is an attenuated viral vector or a  Salmonella typhi  vector. 
     
     
         94 . The vector of  claim 76 , further encoding an immunomodulatory compound. 
     
     
         95 . The vector of  claim 94 , wherein the immunomodulatory compound is a cytokine, chemokine, or complement component that enhances expression of immune system accessory or adhesion molecules, their receptors, or a combination thereof. 
     
     
         96 . The vector of  claim 94 , wherein the immunomodulatory compound is any of interleukins 1 to 15, interferons 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, or macrophage inflammatory peptides MIP-1a or MIP-1b. 
     
     
         97 . A vaccine comprising the vector of  claim 76 . 
     
     
         98 . The vaccine of  claim 97  further comprising an adjuvant, carrier or antigen presenting cell. 
     
     
         99 . The vaccine of  claim 98  wherein the 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.