Engineered immune-mobilizing T-cell receptors with enhanced affinity for HIV-1 gag
AssigneeImmunocore Limited
InventorsTara Mahon, Yi Li
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Abstract
The present invention relates to T cell receptors (TCRs) which bind the HLA-A*02 restricted peptide SLYNTVATL (SEQ ID NO: 1) derived from the HIV Gag gene product, p17. Said TCRs comprise non-natural mutations within the alpha and/or beta variable domains relative to a native HIV TCR. The TCRs of the invention possess unexpectedly high affinity, specificity and sensitivity for a complex of SEQ ID NO: 1 and HLA-A*02, and drive a particularly potent T cell response. Such TCRs are particularly useful in the development of soluble immunotherapeutic reagents for the treatment of HIV infected individuals.
Claims6
A soluble T cell receptor (TCR)-anti-CD3 fusion molecule that specifically binds to SLYNTVATL (SEQ ID NO:
- 1) in complex with HLA-A*02 comprising a TCR alpha chain comprising a TCR alpha chain variable domain and a TCR beta chain comprising a TCR beta chain variable domain, wherein
- (i) the TCR alpha chain variable domain comprises an amino acid sequence comprising at least 94% sequence identity to SEQ ID NO:
- 6;
- and
- (ii) the TCR beta chain variable domain comprises an amino acid sequence comprising the sequence of SEQ ID NO:
- 8;
- wherein an anti-CD3 antibody is covalently linked to the N-terminus or the C-terminus of the TCR beta chain.
Dependencies are inferred from the claim text.