Combination therapy with wt1 peptide vaccine and temozolomide

Abstract

The present invention relates to combination therapy for cancer with a WT1 peptide vaccine and temozolomide.

1 . A method for treating cancer, comprising administering therapeutically effective doses of a WT1 peptide and temozolomide to a patient in need thereof. 
     
     
         2 . The method according to  claim 1 , wherein the WT1 peptide is a peptide selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO. 2) 
                 
                     
                   Cys Tyr Thr Trp Asn Gln Met Asn Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 3) 
                 
                     
                   Arg Met Phe Pro Asn Ala Pro Tyr Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 4) 
                 
                     
                   Tyr Met Phe Pro Asn Ala Pro Tyr Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 5) 
                 
                     
                   Ser Leu Gly Glu Gln Gln Tyr Ser Val; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and
 a peptide comprising one or two amino acid substitutions, deletions or additions of SEQ ID Nos: 2, 3, 4, or 5. 
 
     
     
         3 - 6 . (canceled) 
     
     
         7 . The method according to  claim 1 , wherein the WT1 peptide consists of Arg Met Phe Pro Asn Ala Pro Tyr Leu (SEQ ID NO. 3). 
     
     
         8 . The method according to  claim 1 , wherein the WT1 peptide consists of Tyr Met Phe Pro Asn Ala Pro Tyr Leu (SEQ ID NO. 4). 
     
     
         9 . The method according to  claim 1 , wherein the WT1 peptide consists of Ser Leu Gly Glu Gln Gln Tyr Ser Val (SEQ ID NO. 5). 
     
     
         10 . The method according to  claim 1 , wherein the WT1 peptide is a peptide in which a cysteine residue is added at the N terminal end of the peptide selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO. 3) 
                 
                     
                   Arg Met Phe Pro Asn Ala Pro Tyr Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 4) 
                 
                     
                   Tyr Met Phe Pro Asn Ala Pro Tyr Leu;  
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 5) 
                 
                     
                   Ser Leu Gly Glu Gln Gln Tyr Ser Val. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         11 . The method according to  claim 10 , wherein the cysteine is added by condensing a thiol group of the cysteine and a thiol group of the cysteine residue in the peptide via disulfide bonding. 
     
     
         12 . The method according to  claim 1 , wherein the WT1 peptide is a peptide dimer in which two peptide monomers are bonded together via disulfide bonding between thiol groups, and the two peptide monomers are selected from the group consisting of 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO. 2) 
                 
                     
                   Cys Tyr Thr Trp Asn Gln Met Asn Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 3) 
                 
                     
                   Arg Met Phe Pro Asn Ala Pro Tyr Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 4) 
                 
                     
                   Tyr Met Phe Pro Asn Ala Pro Tyr Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 5) 
                 
                     
                   Ser Leu Gly Glu Gln Gln Tyr Ser Val; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and
 a peptide comprising one or two amino acid substitutions, deletions or additions of SEQ ID Nos: 2, 3, 4, or 5. 
 
     
     
         13 . The method according to  claim 12 , wherein the peptide monomers are selected from the group consisting of: 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO. 2) 
                 
                     
                   Cys Tyr Thr Trp Asn Gln Met Asn Leu, 
                 
             
                
                
               
            
           
         
       
       and
 a peptide in which a cysteine residue is added at the N terminal end of the peptide selected from the group consisting of: 
 
       
         
           
                 
                 
               
                     
                   (SEQ ID NO. 3) 
                 
                     
                   Arg Met Phe Pro Asn Ala Pro Tyr Leu; 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 4) 
                 
                     
                   Tyr Met Phe Pro Asn Ala Pro Tyr Leu;  
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO. 5) 
                 
                     
                   Ser Leu Gly Glu Gln Gln Tyr Ser Val. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         14 . The method according to  claim 1 , wherein the WT1 peptide is a peptide dimer of SEQ ID NO: 3, each monomer of SEQ ID NO:3 has a cysteine at the N-terminal end of the peptide and is bonded together via disulfide bonding between thiol groups of the cysteine. 
     
     
         15 . The method according to  claim 1 , wherein the WT1 peptide is a peptide dimer of SEQ ID NO: 2 and SEQ ID NO:3, each of SEQ ID NO:2 and SEQ ID NO:3 has a cysteine at the N-terminal end and bonded together via disulfide bonding between thiol groups of the cysteine on each of SEQ ID NO:2 and SEQ ID NO:3. 
     
     
         16 . The method according to  claim 1 , wherein the cancer is glioma. 
     
     
         17 . The method according to  claim 1 , wherein the WT1 peptide and temozolomide are administered to a patient having received extirpative surgery for a tumor. 
     
     
         18 . The method according to  claim 1 , wherein the WT1 peptide and temozolomide are administered to a patient having received radiation therapy. 
     
     
         19 . The method according to  claim 1 , wherein the WT1 peptide and temozolomide are administered to a patient having received a combination therapy of radiation therapy and temozolomide.