T-cell receptors that recognize frame-shift mutants of TGF beta RII

摘要

The present invention is directed to a TCR molecule that recognizes a neopeptide produced as a result of a cancer-associated "-1A" frame-shift mutation in human TGFβRII. When the peptide is presented by class I MHC, the TCR molecule can bind the peptide of SEQ ID NO: 1, including the? -Chain domain and? -Chain domain, wherein each of the chain domains comprises three CDR sequences A) CDRs 1, 2 and 3 of the a-chain domain have the respective sequences of SEQ ID NOS: 2, 3 and 4; b) CDRs 1, 2 and 3 of the? -chain domain have the respective sequences of SEQ ID NOS: 5, 6 and 7, and wherein one or more of the CDR sequences are optionally modified by substitution, addition or deletion of one or two amino acids . Nucleic acid molecules encoding such TCRs are provided, as are soluble TCR molecules with these CDR sequences. The nucleic acid molecule of the present invention can be used to transform an immune effector cell to express a TCR as defined herein and such modified immune effector cells can be used for the treatment of cancer such as soluble TCRs, It is useful in therapy.