abstract |
The present invention relates to TCR molecules which recognise neopeptides produced as a result of the cancer-associated "-1A" frameshift mutation in human TGFβRII. The TCR molecules are capable of binding a peptide of SEQ ID NO: 1 when said peptide is presented by a Class I MHC, and comprise an α-chain domain and a β-chain domain, each chain domain comprising three CDR sequences, wherein a) CDRs 1, 2 and 3 of the α-chain domain have the sequences of SEQ ID NOs: 2, 3 and 4 respectively; and b) CDRs 1, 2 and 3 of the β-chain domain have the sequences of SEQ ID NOs: 5, 6 and 7 respectively, and wherein one or more of said CDR sequences may optionally be modified by substitution, addition or deletion of 1 or 2 amino acids. Nucleic acid molecules encoding such TCRs are provided, as are soluble TCR molecules with these CDR sequences. The nucleic acid molecules of the invention can be used to modify immune effector cells to express a TCR as defined herein, and such modified immune effector cells are useful in therapy for cancer, as are soluble TCRs as defined above. |