Hla-Dr-Binding Antigen Peptide Derived From Wt1

Abstract

The present invention provides a WT1-derived HLA-DRB1*0405-binding antigen peptide, a polynucleotide encoding said peptide, a helper T cell inducer comprising said peptide or polynucleotide, and the like. It is related to a partial peptide consisting of 10-25 contiguous amino acids in the amino acid sequence of human WT1 shown in SEQ ID NO: 1, which binds to HLA-DRB1*0405 and induces helper T cells, a polynucleotide encoding said peptide, or a helper T cell inducer comprising said peptide or polynucleotide.

1 . A peptide consisting of 10-25 contiguous amino acids in the amino acid sequence of human WT1 shown in SEQ ID NO: 1, which binds to HLA-DRB1*0405 and induces helper T cells. 
     
     
         2 . The peptide of  claim 1 , which comprises an amino acid sequence set forth in any one of SEQ ID NOS: 2-23. 
     
     
         3 . The peptide of  claim 2 , which comprises the amino acid sequence set forth in SEQ ID NO: 24. 
     
     
         4 . A peptide of 10-25 amino acids, which comprises an amino acid sequence wherein the amino acid residue at position 1, 4, 6 and/or 9 of an amino acid sequence set forth in any one of SEQ ID NOS: 2-23 is substituted by another amino acid residue, and which binds to an HLA-DRB1*0405 and induces helper T cells. 
     
     
         5 . The peptide of  claim 4 , which comprises an amino acid sequence wherein the amino acid residue at position 1, 4, 6 and/or 9 of an amino acid sequence set forth in any one of SEQ ID NOS: 2-23 is substituted by an amino acid residue selected from the following amino acids:
 phenylalanine, tyrosine, tryptophan, valine, isoleucine, leucine and methionine for the position 1;   valine, isoleucine, leucine, methionine, aspartic acid and glutamic acid for the position 4;   asparagine, serine, threonine, glutamine, lysine and aspartic acid for the position 6; and   aspartic acid, glutamic acid and glutamine for the position 9.   
     
     
         6 . The peptide of  claim 5 , which comprises an amino acid sequence wherein the amino acid residue at position 3, 6, 8 and/or 11 of the amino acid sequence set forth in SEQ ID NO: 24 is substituted by an amino acid residue selected from the following amino acids:
 phenylalanine, tryptophan, valine, isoleucine, leucine and methionine for the position 3;   valine, isoleucine, methionine, aspartic acid and glutamic acid for the position 6;   asparagine, serine, threonine, glutamine, lysine and aspartic acid for the position 8; and   aspartic acid, glutamic acid and glutamine for the position 11.   
     
     
         7 . A peptide comprising a peptide described in  claim 1  together with a cancer antigen peptide. 
     
     
         8 . A polynucleotide encoding a peptide described in  claim 1 . 
     
     
         9 . An expression vector containing the polynucleotide described in  claim 8 . 
     
     
         10 . A cell containing the expression vector described in  claim 9 . 
     
     
         11 . A process for producing a peptide described in  claim 1 , which comprises culturing the cell described in  claim 10  under the condition where the peptide can be expressed. 
     
     
         12 . An antibody which specifically binds to a peptide described in  claim 1 . 
     
     
         13 . A pharmaceutical composition which comprises a peptide described in  claim 1 , an expression vector described in  9  or a cell described in  claim 10 , in association with a pharmaceutically acceptable carrier. 
     
     
         14 . The pharmaceutical composition of  claim 13 , which is a therapeutic or preventive agent for cancer. 
     
     
         15 . The pharmaceutical composition of  claim 13 , which is an inducer of helper T cells, and which comprises a peptide described in  claim 1 ; an expression vector described in  claim 9  related to a peptide of  claim 1 ; or a cell described in  claim 10  related to a peptide of  claim 1 , in association with a pharmaceutically acceptable carrier. 
     
     
         16 . The pharmaceutical composition of  claim 13 , which is an enhancer of cancer vaccine efficacy, and which comprises a peptide described in  claim 1 ; an expression vector described in  claim 9  related to a peptide of  claim 1 ; or a cell described in  claim 10  related to a peptide of  claim 1 , in association with a pharmaceutically acceptable carrier. 
     
     
         17 . The pharmaceutical composition of  claim 13 , which is a therapeutic or preventive agent for cancer, and which comprises a peptide described in  claim 7 ; an expression vector described in  claim 9  related to a peptide of  claim 7 ; or a cell described in  claim 10  related to a peptide of  claim 7 , in association with a pharmaceutically acceptable carrier. 
     
     
         18 . (canceled) 
     
     
         19 . A method of treating or preventing cancer, which comprises administering a peptide described in  claim 1 , an expression vector described in  claim 9  or a cell described in  claim 10  to a subject in need thereof. 
     
     
         20 . A pharmaceutical composition which comprises a peptide described in  claim 1  in combination with a cancer antigen peptide. 
     
     
         21 . The pharmaceutical composition of  claim 20 , which is used for treating or preventing cancer. 
     
     
         22 . A kit for treating or preventing cancer, which comprises a pharmaceutical composition comprising a peptide of  claim 1  in association with a pharmaceutically acceptable carrier, and a pharmaceutical composition comprising a cancer antigen peptide in association with a pharmaceutically acceptable carrier. 
     
     
         23 . (canceled) 
     
     
         24 . A method of treating or preventing cancer, which comprises administering a peptide of  claim 1  in combination with a cancer antigen peptide to a subject in need thereof.