High affinity T cell receptor and use thereof
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. An isolated nucleic acid molecule coding for the V(D)J regions of a T cell receptor (TCR) that recognizes tyrosinase and 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, wherein the α- and β-chain coding sequence is derived from SEQ ID NO: 1 and SEQ ID NO: 2, respectively, by codon optimization,
or
a fragment thereof coding for a CDR3 region of a TCR recognizing tyrosinase 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.
2. The isolated nucleic acid molecule of claim 1 , wherein the derivative of the α- and β-chain coding sequence is derived from SEQ ID NO: 1 and 2, respectively, by codon optimization and comprises the nucleic acid sequence of SEQ ID NO: 7 coding for the α-chain and comprises the nucleic acid sequence of SEQ ID NO: 8 coding for the β-chain of said TCR.