Cancer antigen-specific t-cell receptor gene, peptide encoded by the gene, and use of them

Abstract

Disclosed are: a nucleotide sequence and an amino acid sequence for CDR3 region of T-cell receptor (TCR) gene of WT1-specific cytotoxic T-cell (CTL) for WT1 protein; a method for the detection or treatment of cancer using the nucleotide sequence or the amino acid sequence; and a chip, a primer set, a kit, an apparatus and the like for use in the detection of cancer, each of which comprises the nucleotide sequence or the amino acid sequence.

1 . A method for assaying the clonality of a WT1-specific CTL, comprising:
 (a) sorting single WT1-specific CTLs in a sample;   (b) contacting a peptide from a single WT1-specific CTL with an antibody against a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1697-3392; and   (c) measuring the clonality of WT1-specific CTLs that comprise an identical amino acid sequence selected from the group consisting of SEQ ID NOs: 1697-3392, thereby characterizing said WT1-specific CTLs as having a multiplicity of clonality if said clonality is greater than 1; and/or   measuring the number of types of WT1-specific CTLs that have a multiplicity of clonality.   
     
     
         2 . The method of  claim 1 , wherein the antibody in step (b) is immobilized on a chip. 
     
     
         3 . A method for diagnosing cancer in an HLA-A*2402-positive subject, comprising assaying the clonality of a WT1-specific CTL using the method of  claim 1  in a sample obtained from the subject before a therapy,
 wherein the subject is determined to have an increased possibility of developing cancer when a WT1-specific CTL having a multiplicity of clonality is present. 
 
     
     
         4 . The method of  claim 3 , wherein an increased clonality of WT1-specific CTLs having a clonality of 3 or more, or an increasingly abundant number of types of WT1-specific CTLs having a clonality of 3 or more, indicates an increased possibility of developing cancer. 
     
     
         5 . A method for testing the sensitivity of an HLA-A*2402-positive subject to WT1 peptide immunotherapy, comprising assaying the clonality of a WT1-specific CTL using the method of  claim 1  in a first sample obtained from the subject before the immunotherapy and in a second sample obtained from a subject non-responsive to the immunotherapy,
 wherein the subject is determined to have sensitivity to the immunotherapy when the types of WT1-specific CTLs having a multiplicity of clonality in the subject are more abundant than in the subject non-responsive to the immunotherapy. 
 
     
     
         6 . The method of  claim 5 , wherein an increasingly abundant number of types of WT1-specific CTLs having a multiplicity of clonality indicates an increased sensitivity to the immunotherapy. 
     
     
         7 . A method for monitoring WT1 peptide immunotherapy in an HLA-A*2402-positive subject, comprising assaying the clonality of a WT1-specific CTL using the method of  claim 1  in a first sample obtained from the subject before the immunotherapy and in a second sample obtained from the subject after the immunotherapy,
 wherein the subject is determined to have responded to the immunotherapy when the clonality of a WT1-specific CTL increases after the immunotherapy compared to before the immunotherapy. 
 
     
     
         8 . The method of  claim 7 , wherein an increased clonality of WT1-specific CTLs after the immunotherapy, or an increasingly abundant number of types of WT1-specific CTLs having a multiplicity of clonality after the immunotherapy, indicates increased responsiveness to the immunotherapy.