Non-naturally occurring T cell receptors

A non-naturally occurring T cell receptor (TCR) that binds to a YLEPGPVTA (SEQ ID NO:

• 1)-HLA-A2 complex comprising a TCR alpha chain variable domain and a TCR beta chain variable domain, wherein:
• (a) the alpha chain variable domain has
• (i) at least 90% sequence identity to the amino acid sequence comprising amino acids 1 to 109 of SEQ ID NO:
• 2, or
• (ii) at least 90% sequence identity to the amino acids 1 to 109 of SEQ ID NO:
• 2 and has a mutation at one or more positions selected from the group consisting of:
• 94D, 97L, 98V and 102G;
• (b) the beta chain variable domain has
• (i) amino acids 1 to 112 of SEQ ID NO:
• 3, and a mutation at one or more positions selected from the group consisting of:
• 27L, 28N, 29H, 30D, 31A, 50Q, 51I, 52V, 53N, 54D, 61A, 94S, 95I, 96G, 97G, 98P and 100E, or
• (ii) at least 90% sequence identity to the amino acid sequence comprising amino acids 1 to 112 of SEQ ID NO:
• 3;
• (c) the TCR has a binding affinity for, and/or a binding half-life for, the YLEPGPVTA-(SEQ ID NO:
• 1) HLA-A2 complex which is at least double that of a reference TCR, the reference TCR having an extracellular alpha chain sequence of SEQ ID NO:
• 45 and an extracellular beta chain sequence of SEQ ID NO:
• 46;
• and
• (d) at least one of the alpha and beta chain variable domains has at least one mutation.