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 . An isolated peptide selected from
 SGQAYMFPNAPYLPSCLES (SEQ ID No: 41) and QAYMFPNAPYLPSCL (SEQ ID No: 42).   
     
     
         2 .- 13 . (canceled) 
     
     
         14 . A composition comprising the isolated peptide of  claim 1  and a physiologically acceptable carrier. 
     
     
         15 . The composition of  claim 14 , wherein the composition is a vaccine and further comprises an adjuvant or a carrier, or an antigen presenting cell. 
     
     
         16 . The composition of  claim 14 , further comprising an additional WT1 peptide other than said isolated peptide. 
     
     
         17 . The composition of  claim 16 , wherein said 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), and PGCNKRYFKLSHLQMHSRKHTG (SEQ ID No: 4). 
     
     
         18 . A method of inducing formation and proliferation of a WT1 protein-specific cytotoxic T lymphocyte (CTL), the method comprising contacting a lymphocyte population with the composition of  claim 14 , thereby inducing formation and proliferation of a WT1 protein-specific CTL. 
     
     
         19 . 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 composition of  claim 14 , thereby inducing formation and proliferation of both (a) a WT1 protein-specific CD8 +  lymphocyte; and (b) a CD4 +  lymphocyte specific for said WT1 protein. 
     
     
         20 . A method of treating a subject with a WT1-expressing cancer, the method comprising administering to said subject the composition of  claim 14 , thereby treating a subject with a WT1-expressing cancer. 
     
     
         21 . The method of  claim 20 , 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), an ovarian cancer, or a lymphoma. 
     
     
         22 . 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 composition of  claim 14 , thereby reducing an incidence of a WT1-expressing cancer, or its relapse, in a subject. 
     
     
         23 . The method of  claim 22 , 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), an ovarian cancer, or a lymphoma. 
     
     
         24 . An antigen-presenting cell comprising the isolated peptide of  claim 1 . 
     
     
         25 . A vaccine comprising the antigen-presenting cell of  claim 24 . 
     
     
         26 . A nucleic acid molecule encoding the isolated peptide of  claim 1 . 
     
     
         27 . A vaccine comprising the nucleic acid molecule of  claim 26 . 
     
     
         28 . A vector comprising the nucleic acid molecule of  claim 26 . 
     
     
         29 .- 33 . (canceled) 
     
     
         34 . 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 composition comprising the isolated peptide SGQARMFPNAPYLPSCLES (SEQ ID NO:39), thereby inducing formation and proliferation of CTL specific for a WT1-expressing cell. 
     
     
         35 . (canceled) 
     
     
         36 . A method of treating a subject with a WT1-expressing cancer, the method comprising administering to said subject the a composition comprising the isolated peptide SGQARMFPNAPYLPSCLES (SEQ ID NO:39), thereby treating a subject with a WT1-expressing cancer. 
     
     
         37 . The method of  claim 36 , 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), an ovarian cancer, or a lymphoma. 
     
     
         38 - 76 . (canceled)