Therapeutically Useful Molecules

Abstract

A T cell receptor molecule (TCR) containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarily determining regions (CDRs): CDR1α: SSYSPS CDR2α: YTSAATL CDR3α: VVSPFSGGGADGLT or comprising or consisting of SPPSGGGADGLT and the beta chain portion contains three complementarity determining regions (CDRs): CDR1β: DFQATT CDR2β: SNEGSKA CDR3β: comprising SARDGGEG or comprising or consisting of RDGGEGSETQY, or wherein up to three amino acid residues in one or more CDRs are replaced by another amino acid residue. The invention also includes polynucleotides encoding the TCR molecules, and host cells containing the said polynucleotides. Patient derived T cells may have the polynucleotides encoding the TCR molecules introduced therein, and the engineered T cells may be introduced into the patient in order to combat a WT1-expressing malignancy.

1 . A T cell receptor (TCR) molecule containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarity determining regions (CDRs): CDR1α: SSYSPS (SEQ ID NO: 2); CDR2α: YTSAATL (SEQ ID NO: 3); and CDR3α: VVSPFSGGGADGLT (SEQ ID NO: 4) or comprising or consisting of SPFSGGGADGLT (SEQ ID NO: 5) and the beta chain portion contains three complementarity determining regions (CDRs): CDR1β: DFQATT (SEQ ID NO: 6); CDR2β: SNEGSKA (SEQ ID NO: 5); and CDR3β: comprising SARDGGEG (SEQ ID NO: 8) or comprising or consisting of RDGGEGSETQY (SEQ ID NO: 9), or wherein up to one amino acid residue in one or more of the CDRs are replaced by another amino acid residue. 
     
     
         2 . A TCR molecule according to  claim 1  wherein CDR3α has the amino acid sequence VVSPFSGGGADGLT (SEQ ID NO: 4). 
     
     
         3 . A TCR molecule according to  claim 1  wherein CDR3α has the amino acid sequence SPFSGGGADGLT (SEQ ID NO: 5). 
     
     
         4 . A TCR molecule according to  claim 1  wherein CDR3β has the amino acid sequence SARDGGEG (SEQ ID NO: 8). 
     
     
         5 . A TCR molecule according to  claim 1  wherein the CDR3β has the amino acid sequence RDGGEGSETQY (SEQ ID NO: 9). 
     
     
         6 . A TCR molecule according to  claim 1  wherein the alpha chain portion and the beta chain portion are present on different polypeptide chains. 
     
     
         7 . A TCR molecule according to  claim 1  wherein the alpha chain portion and the beta chain portion are present in the same polypeptide chain. 
     
     
         8 . A TCR molecule according to  claim 1  wherein the CDRs are grafted to a human framework region. 
     
     
         9 . A TCR molecule according to  claim 8  wherein the alpha chain portion has the amino acid sequence given in  FIG. 2 . 
     
     
         10 . A TCR molecule according to  claim 8  wherein the beta chain portion has the amino acid sequence given in  FIG. 4 . 
     
     
         11 . A TCR molecule according to  claim 1  which is soluble. 
     
     
         12 - 19 . (canceled) 
     
     
         20 . A method of combating a WT1-expressing malignancy in a patient, the method comprising introducing into the patient a T cell, preferably derived from the patient, which is modified to express the TCR molecule of  claim 1 . 
     
     
         21 . A method according to  claim 20  comprising (1) obtaining T cells from the patient, (2) introducing into the T cells the TCR molecule of  claim 1 , and (3) introducing the cells from step (2) into the patient. 
     
     
         22 . The method according to  claim 20  wherein the WT1-expressing malignancy is any one or more of breast cancer, colon cancer, lung cancer, leukaemia, ovarian cancer, melanoma, head and neck cancer, thyroid cancer, glioblastoma and sarcoma. 
     
     
         23 - 27 . (canceled)