Chimeric antigen receptor

Abstract

A chimeric antigen receptor is provided, including a target antigen-binding region; a transmembrane region; and a T cell activation signal transduction region, in which the target antigen is ganglioside GM2.

1 . A chimeric antigen receptor, comprising:
 a target antigen-binding region; a transmembrane region; and a T cell activation signal transduction region,   wherein the target antigen is ganglioside GM2.   
     
     
         2 . The chimeric antigen receptor according to  claim 1 , wherein the target antigen-binding region includes a heavy-chain variable region and a light-chain variable region of an anti-ganglioside GM2 antibody. 
     
     
         3 . The chimeric antigen receptor according to  claim 2 ,
 wherein the anti-ganglioside GM2 antibody is an antibody selected from the group consisting of the following (a) to (c):   (a) an antibody that includes a heavy-chain variable region comprising CDR1, CDR2, and CDR3 of a heavy-chain variable region consisting of an amino acid sequence set forth in SEQ ID NO: 2, and a light-chain variable region comprising CDR1, CDR2, and CDR3 of a light-chain variable region consisting of an amino acid sequence set forth in SEQ ID NO: 4, and that has a binding ability to ganglioside GM2;   (b) an antibody that includes a heavy-chain variable region consisting of an amino acid sequence in which one or several amino acids are mutated in the amino acid sequence set forth in SEQ ID NO: 2, and a light-chain variable region consisting of an amino acid sequence in which one or several amino acids are mutated in the amino acid sequence set forth in SEQ ID NO: 4, and that has a binding ability to ganglioside GM2; and   (c) an antibody that includes a heavy-chain variable region consisting of an amino acid sequence having 70% or more sequence identity to the amino acid sequence set forth in SEQ ID NO: 2, and a light-chain variable region consisting of an amino acid sequence having 70% or more sequence identity to the amino acid sequence set forth in SEQ ID NO: 4, and that has a binding ability to ganglioside GM2.   
     
     
         4 . The chimeric antigen receptor according to  claim 3 , wherein the heavy-chain variable region includes the amino acid sequence set forth in SEQ ID NO: 2, and the light-chain variable region includes the amino acid sequence set forth in SEQ ID NO: 4. 
     
     
         5 . The chimeric antigen receptor according to  claim 2 , wherein the anti-ganglioside GM2 antibody is a single-stranded antibody (scFv). 
     
     
         6 . The chimeric antigen receptor according to  claim 5 , wherein the scFv is a polypeptide selected from the group consisting of the following (a) to (c):
 (a) a polypeptide that includes an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 12, 14, and 16;   (b) a polypeptide that consists of an amino acid sequence having 70% or more sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 12, 14, and 16, and that has a binding ability to ganglioside GM2; and   (c) a polypeptide that consists of an amino acid sequence in which one or several amino acids are mutated in an amino acid sequence selected from the group consisting of SEQ ID NOs: 10, 12, 14, and 16, and that has a binding ability to ganglioside GM2.   
     
     
         7 . A cell which expresses the chimeric antigen receptor according to  claim 1 . 
     
     
         8 . (canceled) 
     
     
         9 . The cell according to  claim 7 , which expresses both IL-7 and CCL19. 
     
     
         10 . The cell according to  claim 7 , wherein the cell is an immune cell. 
     
     
         11 . A polynucleotide comprising a base sequence that encodes the chimeric antigen receptor according to  claim 1 . 
     
     
         12 . (canceled) 
     
     
         13 . The polynucleotide according to  claim 11 , comprising both a base sequence that encodes IL-7 and a base sequence that encodes CCL19. 
     
     
         14 . A vector comprising a base sequence that encodes the chimeric antigen receptor according to  claim 1 . 
     
     
         15 . (canceled) 
     
     
         16 . The vector according to  claim 14 , comprising both a base sequence that encodes IL-7 and a base sequence that encodes CCL19. 
     
     
         17 . A method for producing a cell expressing a chimeric antigen receptor, comprising introducing a polynucleotide or a vector that includes a base sequence encoding the chimeric antigen receptor according to  claim 1  into the cell. 
     
     
         18 . The method for producing a cell expressing a chimeric antigen receptor according to  claim 17 , further comprising introducing a polynucleotide or a vector that includes at least one of a base sequence encoding IL-7 or a base sequence encoding CCL19 into the cell. 
     
     
         19 . The method for producing a cell expressing a chimeric antigen receptor according to  claim 18 , comprising introducing a polynucleotide or a vector that includes both a base sequence encoding IL-7 and a base sequence encoding CCL19 into the cell. 
     
     
         20 . A pharmaceutical composition comprising the cell according to  claim 7 . 
     
     
         21 . The pharmaceutical composition according to  claim 20 , which is a pharmaceutical composition for treating or preventing a tumor. 
     
     
         22 . A method for treating or preventing a tumor, comprising administering the cell according to  claim 7  to a subject.