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 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 . A method of treatment of cancer comprising administering to a subject suffering such cancer an effective amount of a recombinant TCR having the α chain extracellular sequence SEQ ID NO: 1 and the β chain extracellular sequence SEQ ID NO: 2 except that amino acids Q51 and S53 of SEQ ID NO: 1 are replaced by 51M and 53H and amino acid G50 of SEQ ID NO: 2 is replaced by 50S. 
     
     
         2 . A method of treatment of cancer comprising administering to a subject suffering such cancer an effective amount of a recombinant TCR having the α chain extracellular sequence SEQ ID NO: 1 and the β chain extracellular sequence SEQ ID NO: 2 except that amino acids Q51 and S53 of SEQ ID NO: 1 are replaced by 51M and 53H and amino acid A51 of SEQ ID NO: 2 is replaced by 51V. 
     
     
         3 . The method of  claim 1  or  2 , wherein the TCR is associated with a therapeutic agent. 
     
     
         4 . A method of treatment of cancer comprising administering to a subject suffering such cancer a pharmaceutical composition comprising: a plurality of cells having a recombinant TCR having the α chain extracellular sequence SEQ ID NO: 1 and the β chain extracellular sequence SEQ ID NO: 2 except that amino acids Q51 and S53 of SEQ ID NO: 1 are replaced by 51M and 53H and amino acid G50 of SEQ NO: 2 is replaced by 50S; and a pharmaceutically acceptable carrier. 
     
     
         5 . A method of treatment of cancer comprising administering to a subject suffering such cancer the pharmaceutical composition comprising: a plurality of cells having a recombinant TCR having the α chain extracellular sequence SEQ ID NO: 1 and the β chain extracellular sequence SEQ ID NO: 2 except that amino acids Q51 and S53 of SEQ ID NO: 1 are replaced by 51M and 53H and amino acid A51 of SEQ ID NO: 2 is replaced by 51V; and a pharmaceutically acceptable carrier.