High affinity ny-eso t cell receptors

Abstract

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC SEQ ID NO:126 peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a K D for the said peptide-HLA complex of less than or equal to 1 μM and/or have an off-rate (k off ) of 1×10 −3 S −1 or slower.

1 - 5 . (canceled) 
     
     
         6 . An engineered or recombinant β chain extracellular domain comprising a mutation wherein amino acid 50G of SEQ ID NO: 2 is replaced by 50A. 
     
     
         7 . An engineered or recombinant β chain extracellular domain that comprises the sequence of SEQ ID NO: 2 comprising at least one mutation, wherein the at least one mutation is the substitution of G to A at position 50 using the numbering shown in SEQ ID NO: 2. 
     
     
         8 . An engineered or recombinant T cell receptor (TCR) comprising the β chain extracellular domain of  claim 6  or  7 . 
     
     
         9 . A TCR comprising an α chain extracellular domain and the β chain extracellular domain of  claim 6  or  7 . 
     
     
         10 . The TCR of  claim 9  wherein the α chain extracellular domain comprises the sequence of SEQ ID NO: 1. 
     
     
         11 . An isolated cell comprising the β chain extracellular domain of  claim 6  or  7  or the TCR of  claim 8 ,  9  or  10 . 
     
     
         12 . A pharmaceutical composition comprising a plurality of cells comprising the β chain extracellular domain of  claim 6  or  7  or the TCR of  claim 8 ,  9  or  10 .