T cell receptors and methods of use thereof
AssigneeUniversity Health Network
InventorsNaoto Hirano, Kenji Sugata, Kayoko Saso
Life of this patent
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Abstract
The present disclosure is directed recombinant T cell receptors capable of binding a MUC5AC epitope and nucleic acid molecules encoding the same. In some aspects, 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 aspects, the methods comprise treating a cancer in a subject in need thereof.
Claims19
A nucleic acid molecule comprising:
- (a) a first nucleotide sequence encoding a recombinant T cell receptor (TCR) or an antigen binding portion thereof that specifically binds an epitope of MUC5AC human mucin 5AC (MUC5AC) (“anti-MUC5AC TCR”), wherein the epitope comprises the amino acid sequence set forth in SEQ ID NO:
- 13, which is complexed with an HLA class II molecule HLA-DP4 allele;
- and
- (b) 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-MUC5AC 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;
- wherein:
- (i) the beta chain CDR3 of the anti-MUC5AC TCR comprises the amino acid sequence set forth in SEQ ID NO:
- 10;
- (ii) the beta chain CDR2 of the anti-MUC5AC TCR comprises the amino acid sequence set forth in SEQ ID NO:
- 9;
- (iii) the beta chain CDR1 of the anti-MUCSAC TCR comprises the amino acid sequence set forth in SEQ ID NO:
- 8;
- (iv) the alpha chain CDR3 of the anti-MUC5AC TCR comprises the amino acid sequence set forth in SEQ ID NO:
- 7;
- (v) the alpha chain CDR2 of the anti-MUC5AC TCR comprises the amino acid sequence set forth in SEQ ID NO:
- 6;
- and
- (vi) the alpha chain CDR1 of the anti-MUC5AC TCR comprises the amino acid sequence set forth in SEQ ID NO:
- 5.
Dependencies are inferred from the claim text.