T cell receptors

摘要

A T cell receptor (TCR) having the property of binding to the gp100 YLEPGPVTA peptide-HLA-A2 complex and comprising a TCR alpha variable domain and/or a TCR beta variable domain, characterized in that: (i) said TCR is mutated relative to a TCR having the extracellular alpha and beta chain sequences SEQ ID Nos: 2 and 3 in its alpha chain variable domain amino acids 1 to 109 of SEQ ID No: 2 and/or its beta chain variable domain amino acids 1 to 112 of SEQ ID No: 3; and (ii) said alpha variable domain has at least 90% sequence identity to the amino acid sequence 1 to 109 of SEQ ID No: 2, and/or said beta variable domain has at least 90% sequence identity to the amino acid sequence 1 to 1 12 of SEQ ID No: 3; and (iii) said TCR has a binding affinity for, and/or a binding half-life for, the YLEPGPVTA-HLA-A2 complex at least double that of a reference TCR, the said reference TCR having the extracellular alpha chain sequence SEQ ID No: 45 and the extracellular beta chain sequence SEQ ID No: 46. The use of such TCRs in adoptive therapy, and fusions of such TCRs with therapeutic agents are also described.