T cell receptors and methods of use thereof
AssigneeUniversity Health Network
InventorsNaoto Hirano, Kenji Murata, Kayoko Saso
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Abstract
The present disclosure is directed recombinant T cell receptors capable of binding a gp100 epitope and nucleic acid molecules encoding the same. In some embodiments, the nucleic acid molecules further comprise 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. Other aspects of the disclosure are directed to vectors comprising the nucleic acid molecule and cells comprising the recombinant TCR, the nucleic acid molecule, or the vector. Still other aspects of the disclosure are directed to methods of using the same. In some embodiments, the methods comprise treating a cancer in a subject in need thereof.
Claims15
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 human gp100 (“anti-gp100 TCR”);
- 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,
- wherein the anti-gp100 TCR comprises an alpha chain and a beta chain, wherein the alpha chain comprises a variable region comprising an alpha chain CDR1, an alpha chain CDR2, and an alpha chain CDR3;
- and
- wherein the beta chain comprises variable domain comprising a beta chain CDR1, a beta chain CDR2, and a beta chain CDR3;
- wherein:
- (i) the beta chain CDR3 of the anti-gp100 TCR comprises the amino acid sequence as set forth in SEQ ID NO:
- 10;
- (ii) the beta chain CDR2 of the anti-gp100 TCR comprises the amino acid sequence as set forth in SEQ ID NO:
- 9;
- (iii) the beta chain CDR1 of the anti-gp100 TCR comprises the amino acid sequence as set forth in SEQ ID NO:
- 6;
- (iv) the alpha chain CDR3 of the anti-gp100 TCR comprises the amino acid sequence as set forth in SEQ ID NO:
- 7;
- (v) the alpha chain CDR2 of the anti-gp100 TCR comprises the amino acid sequence as set forth in SEQ ID NO:
- 8;
- and
- (vi) the alpha chain CDR1 of the anti-gp100 TCR comprises the amino acid sequence as set forth in SEQ ID NO:
- 5
- wherein the anti-gp100 TCR cross competes for binding to human gp100 with a reference TCR, which comprises an alpha chain and a beta chain, and wherein the alpha chain comprises an amino acid sequence as set forth in SEQ ID NO:
- 1 and the beta chain comprises an amino acid sequence as set forth in SEQ ID NO:
- 2.
Dependencies are inferred from the claim text.