T cell receptors and methods of use thereof

A nucleic acid molecule comprising:

• (i) a first nucleotide sequence encoding a recombinant T cell receptor (TCR) or an antigen binding portion thereof that specifically binds to tyrosinase (“anti-tyrosinase TCR”);
• wherein the anti-tyrosinase TCR comprises an alpha chain variable domain comprising an alpha chain CDR1, an alpha chain CDR2, and an alpha chain CDR3;
• and a beta chain variable domain comprising a beta chain CDR1, a beta chain CDR2, and a beta chain CDR3;
• and wherein:
• (i) the beta chain CDR3 of the anti-tyrosinase TCR comprises the amino acid sequence set forth in SEQ ID NO:
• 10;
• (ii) the beta chain CDR2 of the anti-tyrosinase TCR comprises the amino acid sequence set forth in SEQ ID NO:
• 9;
• (iii) the beta chain CDR1 of the anti-tyrosinase TCR comprises the amino acid sequence set forth in SEQ ID NO:
• 8;
• (iv) the alpha chain CDR3 of the anti-tyrosinase TCR comprises the amino acid sequence set forth in SEQ ID NO:
• 7;
• (v) the alpha chain CDR2 of the anti-tyrosinase TCR comprises the amino acid sequence set forth in SEQ ID NO:
• 6;
• and
• (vi) the alpha chain CDR1 of the anti-tyrosinase TCR comprises the amino acid sequence set forth in SEQ ID NO:
• 5;
• and
• (ii) a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR.