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US 2022/0031753 A1Published application
T cell receptors
AssigneeAdaptimmune Limited
InventorsNicholas Tribble, William Lawrance, Eleanor Bagg
Life of this patent
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Abstract
The present invention relates to T cell receptors (TCRs) which bind the HLA-A*0201 restricted peptide GVYDGREHTV (SEQ ID NO: 1) derived from the MAGE-A4 protein. The TCRs of the invention demonstrate excellent specificity profiles for this MAGE epitope. Also provided are nucleic acids encoding the TCRs, cells engineered to present the TCRs, cells harbouring expression vectors encoding the TCRs and pharmaceutical compositions comprising the TCRs, nucleic acids or cells of the invention.
Claims19
A T cell receptor (TCR) having the property of binding to GVYDGREHTV (SEQ ID NO:
- 1) in complex with HLA-A*0201 with a dissociation constant of from about 0.05 μM to about 20.0 μM when measured with surface plasmon resonance at 25° C. and at a pH between 7.1 and 7.5 using a soluble form of the TCR, and has at least a ten-fold selectivity of binding to SEQ ID NO:1 in complex with HLA-A*0201 over binding to GVYDGEEHSV (SEQ ID NO:
- 2) in complex with HLA-A*0201 wherein the TCR comprises a TCR alpha chain variable domain and a TCR beta chain variable domain, and wherein the TCR variable domains form contacts with at least residues V2, Y3 and D4 of GVYDGREHTV (SEQ ID NO:
- 1).
A cell harboring
- (a) a TCR expression vector which comprises nucleic acid as claimed in claim 13 in a single open reading frame, or two distinct open reading frames encoding the alpha chain and the beta chain respectively;
- or
- (b) a first expression vector which comprises nucleic acid encoding the alpha chain of a TCR as claimed in claim 1, and a second expression vector which comprises nucleic acid encoding the beta chain of a TCR as claimed in claim 1.
Dependencies are inferred from the claim text.