T cell receptors
AssigneeImmunocore Limited
InventorsConor Hayes, Linda Hibbert, Nathaniel Ross Liddy, Tara Mahon, Marine Raman
Life of this patent
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Abstract
The present invention relates to T cell receptors (TCRs) that bind the HLA-A*02 restricted peptide GVYDGREHTV (SEQ ID NO: 1) derived from the germline cancer antigen MAGE A4. Said TCRs may comprise non-natural mutations within the alpha and/or beta variable domains relative to a native MAGE A4 TCR. The TCRs of the invention are particularly suitable for use as novel immunotherapeutic reagents for the treatment of malignant disease.
Claims18
A method of treating an HLA-A*02 positive human subject, wherein the human subject has tumor cells that express MAGE A4, comprising administering to the human subject a pharmaceutically effective dose of a pharmaceutical composition comprising a T cell receptor (TCR) together with one or more pharmaceutically acceptable carriers or excipients;
- wherein the TCR is a soluble TCR comprising a TCR alpha chain variable domain and a TCR beta chain variable domain, wherein the TCR alpha chain variable domain comprises Complementarity Determining Regions (CDRs) of a CDR1 comprising the sequence VSPFSN (SEQ ID NO:6), a CDR2 comprising the sequence LTFSENT (SEQ ID NO:83), and a CDR3 comprising the sequence VVNSAQGLYIPTF (SEQ ID NO:87), and wherein the TCR beta chain variable domain comprises CDRs of a CDR1 comprising the sequence LDHEN (SEQ ID NO:90), a CDR2 comprising the sequence SRFATG (SEQ ID NO:88), and a CDR3 comprising the sequence ASSSDQNSGDPYEQYF (SEQ ID NO:89).
A method of treating an HLA-A*02 positive human subject, wherein the human subject has tumor cells that express MAGE A4, comprising administering to the subject a pharmaceutically effective dose of a pharmaceutical composition comprising a TCR-anti-CD3 fusion molecule together with one or more pharmaceutically acceptable carriers or excipients;
- wherein the TCR of the TCR-anti-CD3 fusion molecule comprises a TCR alpha chain comprising a TCR alpha chain variable domain and a TCR beta chain comprising a TCR beta chain variable domain;
- wherein the TCR alpha chain variable domain comprises the amino acid sequence of SEQ ID NO:
- 24 and the TCR beta chain variable domain comprises the amino acid sequence of SEQ ID NO:
- 29, and wherein an anti-CD3 antibody is covalently linked to the N-terminus or the C-terminus of the TCR beta chain via a linker sequence selected from the group consisting of SEQ ID NOs:
- 30-37.
Dependencies are inferred from the claim text.