High affinity merkel cell polyomavirus T antigen-specific TCRS and uses thereof
AssigneesFred Hutchinson Cancer Center, University of Washington
InventorsAude G. Chapuis, Paul T. Nghiem, Megan S. McAfee, Natalie J. Miller, Kelly Garneski Paulson, David Martin Koelle, Thomas M. Schmitt, Candice Church
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Abstract
The present disclosure provides binding proteins and TCRs with high affinity and specificity against Merkel cell polyomavirus T antigen epitopes or peptides, T cells expressing such high affinity Merkel cell polyomavirus T antigen specific TCRs, nucleic acids encoding the same, and compositions for use in treating Merkel cell carcinoma.
Claims37
An expression vector comprising a polynucleotide encoding a binding protein, wherein the binding protein comprises:
- (a) a T cell receptor (TCR) α-chain variable (Vα) domain having a CDR3 amino acid sequence of any one of SEQ ID NOS.:13, 44 and 355-364;
- and
- (b) a TCR β-chain variable (Vβ) domain having a CDR3 amino acid sequence of any one of SEQ ID NOS.:14, 69 and 365-374.
A host cell comprising a heterologous polynucleotide encoding a binding protein that is capable of specifically binding to a Merkel cell polyomavirus T antigen peptide:HLA complex, wherein the binding protein comprises:
- (a) a T cell receptor (TCR) α chain variable (Vα) domain having a CDR3 amino acid sequence of any one of SEQ ID NOS.:13, 44, and 355-364, and
- (b) a TCR β chain variable (Vβ) domain having a CDR3 amino acid sequence of any one of SEQ ID NOS.:14, 69, and 365-374.
An isolated polynucleotide encoding a binding protein, wherein the binding protein comprises:
- (a) a T cell receptor (TCR) α-chain variable (Vα) domain having a CDR3 amino acid sequence of any one of SEQ ID NOS.:13, 44 and 355-364;
- and
- (b) a TCR β-chain variable (Vβ) domain having a CDR3 amino acid sequence of any one of SEQ ID NOS.:14, 69 and 365-374,
- wherein the polynucleotide comprises a Vα domain-encoding polynucleotide having at least 80% identity to the polynucleotide sequence of any one of SEQ ID NOs.:5, 6, 375-384 and 395-404, and a Vβ domain-encoding polynucleotide having at least 80% identity to the polynucleotide sequence of any one of SEQ ID NOs.:
- 9, 10, 385-394, and 405-414.
Dependencies are inferred from the claim text.