Novel t-cell receptor

Abstract

Provided is a T cell receptor containing, as α chain complementarity determining regions, respective amino acid sequences of CDR1 to CDR3 respectively shown in SEQ ID NOs: 1 to 3, or respective amino acid sequences of CDR1 to CDR3 respectively shown in SEQ ID NOs: 4 to 6, as β chain complementarity determining regions, respective amino acid sequences of CDR1 to CDR3 respectively shown in SEQ ID NOs: 7 to 9, or respective amino acid sequences of CDR1 to CDR3 respectively shown in SEQ ID NOs: 10 to 12, and capable of binding to a peptide having the amino acid sequence shown in SEQ ID NO: 27 or a complex of the peptide and HLA-A24. A T cell receptor containing, as an α chain complementarity determining regions, respective amino acid sequences of CDR1 to CDR3 respectively shown in SEQ ID NOs: 13 to 15, as β chain complementarity determining regions, respective amino acid sequences of CDR1 to CDR3 respectively shown in SEQ ID NOs: 16 to 18, and capable of binding to a peptide having the amino acid sequence shown in SEQ ID NO: 28 or a complex of the peptide and HLA-A02.

1 . (canceled) 
     
     
         2 . A T cell receptor (TCR) comprising,
 as complementarity determining regions of the α chain,
 the amino acid sequence shown in SEQ ID NO: 13, 
 the amino acid sequence shown in SEQ ID NO: 14, and 
 the amino acid sequence shown in SEQ ID NO: 15, and 
   as complementarity determining regions of the β chain,
 the amino acid sequence shown in SEQ ID NO: 16, 
 the amino acid sequence shown in SEQ ID NO: 17, and 
 the amino acid sequence shown in SEQ ID NO: 18. 
   
     
     
         3 . (canceled) 
     
     
         4 . The T cell receptor (TCR) according to  claim 2  comprising
 as an α chain variable region,
 the amino acid sequence shown in SEQ ID NO: 23, 
 the amino acid sequence shown in SEQ ID NO: 23 wherein one or several amino acids are deleted, substituted or added, or 
 an amino acid sequence having 90% or more identity with the amino acid sequence shown in SEQ ID NO: 23, and 
 
 as a β chain variable region,
 the amino acid sequence shown in SEQ ID NO: 24, 
 the amino acid sequence shown in SEQ ID NO: 24 wherein one or several amino acids are deleted, substituted or added, or 
 an amino acid sequence having 90% or more identity with the amino acid sequence shown in SEQ ID NO: 24. 
 
 
     
     
         5 . The T cell receptor according to  claim 2 , comprising
 as an α chain constant region,
 the amino acid sequence shown in SEQ ID NO: 25, 
 the amino acid sequence shown in SEQ ID NO: 25 wherein one or several amino acids are deleted, substituted or added, or 
 an amino acid sequence having 90% or more identity with the amino acid sequence shown in SEQ ID NO: 25, and 
   as a β chain constant region,
 the amino acid sequence shown in SEQ ID NO: 26, 
 the amino acid sequence shown in SEQ ID NO: 26 wherein one or several amino acids are deleted, substituted or added, or 
 an amino acid sequence having 90% or more identity with the amino acid sequence shown in SEQ ID NO: 26. 
   
     
     
         6 . A nucleic acid encoding the T cell receptor according to  claim 2 . 
     
     
         7 . An expression vector comprising the nucleic acid according to  claim 6 . 
     
     
         8 . An isolated cell comprising the nucleic acid according to  claim 6 . 
     
     
         9 . The isolated cell according to  claim 8 , wherein said cell is a lymphocyte or a pluripotent stem cell. 
     
     
         10 . The isolated cell according to  claim 8 , wherein said cell is a cytotoxic T lymphocyte. 
     
     
         11 . A method of producing an isolated cell according to  claim 8 , comprising a step of introducing the nucleic acid according to  claim 6  or the vector according to  claim 7  into the cell. 
     
     
         12 . A T cell induced from a pluripotent stem cell comprising the nucleic acid according to  claim 6 . 
     
     
         13 . A method of producing a T cell, comprising the following steps:
 (1) a step of differentiating a pluripotent stem cell comprising the nucleic acid according to  claim 6  into a hematopoietic progenitor cell, and   (2) a step of differentiating the hematopoietic progenitor cell into a T cell.   
     
     
         14 . The method according to  claim 13 , wherein said T cell is a cytotoxic T cell, in particular a CD8 positive cytotoxic T cell. 
     
     
         15 . A medicament comprising an isolated cell, wherein the isolated cell comprises a nucleic acid encoding the T cell receptor, wherein the T cell receptor comprises, 
       as complementarity determining regions of the α chain,
 the amino acid sequence shown in SEQ ID NO: 13, 
 the amino acid sequence shown in SEQ ID NO: 14, and 
 the amino acid sequence shown in SEQ ID NO: 15, and 
 
       as complementarity determining regions of the β chain,
 the amino acid sequence shown in SEQ ID NO: 16, 
 the amino acid sequence shown in SEQ ID NO: 17, and 
 the amino acid sequence shown in SEQ ID NO: 18. 
 
     
     
         16 . A method of treating cancer, comprising administering to a subject the medicament according to  claim 15  in which the isolated cell is a lymphocyte or a T cell induced from a pluripotent stem cell comprising a nucleic acid encoding the T cell receptor, and wherein the cancer is associated with expressing glypican-3. 
     
     
         17 . A method for killing a cell expressing glypican-3, comprising administering the isolated cell according to  claim 8  to the cell expressing glypican-3. 
     
     
         18 . (canceled) 
     
     
         19 . A method of treating cancer, comprising administering to a subject the isolated cell comprising a nucleic acid encoding the T cell receptor according to  claim 2 , wherein the cancer is associated with expressing glypican-3, and the isolated cell is a lymphocyte or a T cell induced from a pluripotent stem cell. 
     
     
         20 . A method of making a therapeutic agent for treating a disease expressing glypican-3, comprising inducing a T cell from a pluripotent stem cell comprising a nucleic acid encoding the T cell receptor of  claim 2 .