US2016199472A1PendingUtilityA1

Hla-a* 1101-restricted wt1 peptide and pharmaceutical composition comprising the same

Assignee: INT INST CANCER IMMUNOLOGY INCPriority: Dec 28, 2006Filed: Jan 22, 2016Published: Jul 14, 2016
Est. expiryDec 28, 2026(~0.4 yrs left)· nominal 20-yr term from priority
Inventors:Haruo Sugiyama
A61P 37/02A61P 35/02A61P 37/04A61P 35/00G01N 33/575A61K 2039/57A61K 2039/572A61K 38/00A61K 40/4243A61K 40/11C07K 14/4748G01N 33/574A61K 39/0011A61K 2039/5158A61K 39/001153C07K 14/82C12N 15/11
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Claims

Abstract

An HLA-A*1101-restricted WT1 peptide, specifically, a peptide comprising an amino acid sequence consisting of 9 contiguous amino acids from a WT1 protein, wherein the peptide has an ability to bind to an HLA-A*1101 molecule, and has an ability to induce a CTL is described. A peptide dimer having an ability to bind to an HLA-A*1101 molecule and having an ability to induce a CTL, in which two peptide monomers each comprising an amino acid sequence consisting of 9 contiguous amino acids from a WT1 protein and comprising at least one cysteine residue are bound to each other through a disulfide bond is also described. Furthermore, a polynucleotide encoding the peptide, a pharmaceutical composition for the treatment and/or prevention of a cancer comprising the same and the like are provided.

Claims

exact text as granted — not AI-modified
1 - 19 . (canceled) 
     
     
         20 . A method for the induction of a Wilms' tumor 1 (WT1)-specific cytotoxic T cell (CTL), comprising administering to an HLA-A*1101-positive subject an effective amount of an isolated peptide dimer comprising a first and second peptide monomer bound through a disulfide bond, wherein
 (1) the first peptide monomer consists of an amino acid sequence Thr Gly Val Lys Pro Phe Gln Cys Lys (SEQ ID No: 7) and   (2) the second peptide monomer consists of an amino acid sequence selected from:   
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 3) 
                 
                     
                   Pro Ile Leu Cys Gly Ala Gln Tyr Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 8) 
                 
                     
                   Lys Thr Cys Gln Arg Lys Phe Ser Arg, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 9) 
                 
                     
                   Ser Cys Arg Trp Pro Ser Cys Gln Lys. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         21 . A WT1-specific CTL, which is induced by an isolated peptide and/or an isolated peptide dimer, wherein the isolated peptide consists of an amino acid sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 5) 
                 
                     
                   Ser Ala Ser Glu Thr Ser Glu Lys Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 6) 
                 
                     
                   Ser His Leu Gln Met His Ser Arg Lys, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein the isolated peptide dimer comprises a first and second peptide monomer bound through a disulfide bond, wherein 
         (1) the first peptide monomer consists of an amino acid sequence Thr Gly Val Lys Pro Phe Gln Cys Lys (SEQ ID No: 7) and 
         (2) the second peptide monomer consists of an amino acid sequence selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 3) 
                 
                     
                   Pro Ile Leu Cys Gly Ala Gln Tyr Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 8) 
                 
                     
                   Lys Thr Cys Gln Arg Lys Phe Ser Arg, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 9) 
                 
                     
                   Ser Cys Arg Trp Pro Ser Cys Gln Lys. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         22 . A method for the induction of a WT1-specific CTL, comprising culturing a peripheral blood mononuclear cell in the presence of an isolated peptide and/or an isolated peptide dimer to induce the WT1-specific CTL from the peripheral blood mononuclear cell, wherein the isolated peptide consists of an amino acid sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 5) 
                 
                     
                   Ser Ala Ser Glu Thr Ser Glu Lys Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 6) 
                 
                     
                   Ser His Leu Gln Met His Ser Arg Lys, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein the isolated peptide dimer comprises a first and second peptide monomer bound through a disulfide bond, wherein 
         (1) the first peptide monomer consists of an amino acid sequence Thr Gly Val Lys Pro Phe Gln Cys Lys (SEQ ID No: 7) and 
         (2) the second peptide monomer consists of an amino acid sequence selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 3) 
                 
                     
                   Pro Ile Leu Cys Gly Ala Gln Tyr Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 8) 
                 
                     
                   Lys Thr Cys Gln Arg Lys Phe Ser Arg, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 9) 
                 
                     
                   Ser Cys Arg Trp Pro Ser Cys Gln Lys. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         23 . An antigen-presenting cell presenting a WT1 peptide, which is induced by an isolated peptide and/or an isolated peptide dimer, wherein the isolated peptide consists of an amino acid sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 5) 
                 
                     
                   Ser Ala Ser Glu Thr Ser Glu Lys Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 6) 
                 
                     
                   Ser His Leu Gln Met His Ser Arg Lys, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein the isolated peptide dimer comprises a first and second peptide monomer bound through a disulfide bond, wherein 
         (1) the first peptide monomer consists of an amino acid sequence Thr Gly Val Lys Pro Phe Gln Cys Lys (SEQ ID No: 7) and 
         (2) the second peptide monomer consists of an amino acid sequence selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 3) 
                 
                     
                   Pro Ile Leu Cys Gly Ala Gln Tyr Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 8) 
                 
                     
                   Lys Thr Cys Gln Arg Lys Phe Ser Arg, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 9) 
                 
                     
                   Ser Cys Arg Trp Pro Ser Cys Gln Lys. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         24 . A method for the induction of an antigen-presenting cell presenting a WT1 peptide, comprising culturing an immature antigen-presenting cell in the presence of an isolated peptide and/or an isolated peptide dimer to induce the antigen-presenting cell presenting a WT1 peptide from the immature antigen-presenting cell, wherein the isolated peptide consists of an amino acid sequence selected from: 
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 5) 
                 
                     
                   Ser Ala Ser Glu Thr Ser Glu Lys Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 6) 
                 
                     
                   Ser His Leu Gln Met His Ser Arg Lys, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
         wherein the isolated peptide dimer comprises a first and second peptide monomer bound through a disulfide bond, wherein 
         (1) the first peptide monomer consists of an amino acid sequence Thr Gly Val Lys Pro Phe Gln Cys Lys (SEQ ID No: 7) and 
         (2) the second peptide monomer consists of an amino acid sequence selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID No: 3) 
                 
                     
                   Pro Ile Leu Cys Gly Ala Gln Tyr Arg, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 7) 
                 
                     
                   Thr Gly Val Lys Pro Phe Gln Cys Lys, 
                 
                     
                     
                 
                     
                   (SEQ ID No: 8) 
                 
                     
                   Lys Thr Cys Gln Arg Lys Phe Ser Arg, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID No: 9) 
                 
                     
                   Ser Cys Arg Trp Pro Ser Cys Gln Lys. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         25 . A method for the diagnosis of a cancer, comprising incubating the CTL according to  claim 21  with a sample from an HLA-A*1101-positive subject, or administering the CTL to the HLA-A*1101-positive subject. 
     
     
         26 . The method according to  claim 25 , wherein the CTL is labeled. 
     
     
         27 . A method for the diagnosis of a cancer, comprising incubating the antigen-presenting cell according to  claim 23  with a sample from an HLA-A*1101-positive subject, or administering the antigen-presenting cell to the HLA-A*1101-positive subject. 
     
     
         28 . The method according to  claim 27 , wherein the antigen-presenting cell is labeled.

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