High affinity t cell receptor and use thereof

Abstract

The present invention is directed to a high affinity T cell receptor (TCR) against a tumor-associated antigen, an isolated nucleic acid molecule encoding same, a T cell expressing said TCR, and a pharmaceutical composition for use in the treatment of diseases involving malignant cells expressing said tumor-associated antigen.

1 - 16 . (canceled) 
     
     
         17 . A vector comprising a nucleic acid encoding a T cell receptor (TCR) that binds to a tyrosinase peptide comprising the amino acid sequence of YMDGTMSQV (SEQ ID NO: 9), the nucleic acid comprising the nucleic acid sequence of SEQ ID NO: 1 coding for the α-chain and/or the nucleic acid sequence of SEQ ID NO: 2 coding for the β-chain of said TCR,
 or 
 
       a derivative thereof, coding for the α- or β-chain, wherein the chain has been altered by one or more additions, deletions, or conservative substitutions of from 1-15 amino acids, the additions, deletions, or conservative substitutions being outside the CDR3 region of each chain,
 or 
 
       a fragment thereof coding for a CDR3 region of the TCR and having the nucleic acid sequence of SEQ ID NO: 3 or 4 or coding for the amino acid sequences of SEQ ID NO: 5 or 6. 
     
     
         18 . The vector of  claim 17 , comprising the nucleic acid sequence of SEQ ID NO: 1 coding for the α-chain and/or the nucleic acid sequence of SEQ ID NO: 2 coding for the β-chain of said TCR. 
     
     
         19 . The vector of  claim 18 , comprising the nucleic acid sequence of SEQ ID NO: 1 coding for the α-chain and the nucleic acid sequence of SEQ ID NO: 2 coding for the β-chain of said TCR. 
     
     
         20 . The vector of  claim 17 , wherein the derivative of the α- or β-chain coding sequence is derived from SEQ ID NO: 1 and 2 by codon optimization. 
     
     
         21 . The vector of  claim 20 , wherein the derivative of the α- or β-chain coding sequence comprises the nucleic acid sequence of SEQ ID NO: 7 coding for the α-chain and/or comprises the nucleic acid sequence of SEQ ID NO: 8 coding for the β-chain of said TCR. 
     
     
         22 . The vector of  claim 17 , which is a plasmid, shuttle vector, phagemid, cosmid, expression vector, retroviral vector, adenoviral vector or particle and/or gene therapy vector. 
     
     
         23 . The vector of  claim 22 , which is a plasmid. 
     
     
         24 . The vector of  claim 22 , which is a retroviral vector. 
     
     
         25 . The vector of  claim 17 , further comprising one or more of (i) an origin of replication and (ii) one or more selectable marker genes. 
     
     
         26 . A plasmid comprising a nucleic acid comprising the nucleic acid sequence of SEQ ID NO: 2. 
     
     
         27 . The plasmid of  claim 26 , further comprising an origin of replication and one or more selectable marker genes. 
     
     
         28 . A vector comprising a nucleic acid comprising the nucleic acid sequences of SEQ ID NO: 3 and/or SEQ ID NO:4. 
     
     
         29 . A vector comprising a nucleic acid coding for a TCR binds to a tyrosinase peptide comprising the amino acid sequence of YMDGTMSQV (SEQ ID NO: 9), the TCR comprising the amino acid sequences of SEQ ID NO: 5 and/or 6.