Immunotherapeutic Methods Using Epitopes of WT-1 and GATA-1

Abstract

A peptide comprising the amino acid sequence RMFPNAPYL or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence CMTWNQMNL or a portion or variant thereof provided that the peptide is not intact human WT-1 polypeptide or a peptide comprising the amino acid sequence HLMPFPGPLL or a portion or variant thereof provided that the peptide is not intact human gata-1 polypeptide, and polynucleotides encoding these peptides. The peptides and polynucleotides are useful as cancer vaccines.

1 . An isolated peptide having a molecular weight of 5,000 or less and comprising the amino acid sequence RMFPNAPYL (SEQ ID NO: 1) or comprising an amino acid sequence wherein one or both of the amino acids at positions 2 and 9 of SEQ ID NO: 1 are replaced with another naturally occurring amino acid, wherein the replaced amino acids do not abolish binding to HLA-A0201. 
     
     
         2 - 42 . (canceled) 
     
     
         43 . The peptide of  claim 1  wherein the amino acid sequence of the peptide comprises the amino acid sequence of SEQ ID NO: 1. 
     
     
         44 . The peptide of  claim 1  wherein the amino acid sequence of the peptide comprises an amino acid sequence wherein one or both of the amino acids at positions 2 and 9 of SEQ ID NO: 1 are replaced with another naturally occurring amino acid, wherein the replaced amino acids do not abolish binding to HLA-A0201. 
     
     
         45 . An isolated peptide consisting of 9 to 12 amino acid residues and comprising the amino acid sequence of SEQ ID NO: 1 or comprising an amino acid sequence wherein one or both of the amino acids at positions 2 and 9 of SEQ ID NO: 1 are replaced with another naturally occurring amino acid, wherein the replaced amino acids do not abolish binding to HLA-A0201. 
     
     
         46 . The peptide of  claim 45  wherein the amino acid sequence of the peptide comprises the amino acid sequence of SEQ ID NO: 1. 
     
     
         47 . The peptide of  claim 45  wherein the amino acid sequence of the peptide comprises an amino acid sequence wherein one or both of the amino acids at positions 2 and 9 of SEQ ID NO: 1 are replaced with another naturally occurring amino acid, wherein the replaced amino acids do not abolish binding to HLA-A0201. 
     
     
         48 . A method of killing a target cell that aberrantly expresses a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, the method comprising contacting the target cell with a cytotoxic T lymphocyte (CTL) that recognizes cells that aberrantly express the polypeptide comprising SEQ ID NO: 1, wherein the CTL is activated against the target cell by exposure to an antigen-presenting cell that presents the isolated peptide of  claim 1  or a portion thereof on a class I MHC molecule on the surface of the antigen-presenting cell. 
     
     
         49 . The method of  claim 48  wherein the target cell is a cancer cell. 
     
     
         50 . The method of  claim 49  wherein the cancer cell is selected from the group consisting of a leukemia cell, a breast cancer cell, a melanoma cell, and an ovarian cancer cell, which expresses a WT-1 polypeptide comprising SEQ ID NO: 1. 
     
     
         51 . The method of  claim 48  wherein the CTL and the antigen-presenting cell are allogeneic (allorestricted) with respect to the class I MHC molecule. 
     
     
         52 . The method of  claim 48  wherein the CTL and the antigen-presenting cell are syngeneic (self-restricted) with respect to the class I MHC molecule. 
     
     
         53 . A method of killing a target cell that aberrantly expresses a polypeptide comprising the amino acid sequence of SEQ ID NO: 1, the method comprising contacting the target cell with a cytotoxic T lymphocyte (CTL) that recognizes cells that aberrantly express the polypeptide comprising SEQ ID NO: 1, wherein the CTL is activated against the target cell by exposure to an antigen-presenting cell that presents the isolated peptide of  claim 45  or a portion thereof on a class I MHC molecule on the surface of the antigen-presenting cell. 
     
     
         54 . The method of  claim 53  wherein the target cell is a cancer cell. 
     
     
         55 . The method of  claim 54  wherein the cancer cell is selected from the group consisting of a leukemia cell, a breast cancer cell, a melanoma cell, and an ovarian cancer cell, which expresses a WT-1 polypeptide comprising SEQ ID NO: 1. 
     
     
         56 . The method of  claim 53  wherein the CTL and the antigen-presenting cell are allogeneic (allorestricted) with respect to the class I MHC molecule. 
     
     
         57 . The method of  claim 53  wherein the CTL and the antigen-presenting cell are syngeneic (self-restricted) with respect to the class I MHC molecule.