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.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV12-2 gene product and the beta chain variable domain comprises a TRBV gene product.

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.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs may consist essentially of TCRs which may comprise an alpha chain variable domain from a natural repertoire and a beta chain variable domain from a natural repertoire, wherein the alpha chain variable domain may comprise a TRAV12-2 or a TRAV21 gene product and the beta chain variable domain may comprise a TRBV6 gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV12-2 gene product and the beta chain variable domain comprises a TRBV gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs may consist essentially of TCRs which may comprise an alpha chain variable domain from a natural repertoire and a beta chain variable domain from a natural repertoire, wherein the alpha chain variable domain may comprise a TRAV12-2 or a TRAV21 gene product and the beta chain variable domain may comprise a TRBV6 gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV12-2 gene product and the beta chain variable domain comprises a TRBV gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV17 gene product and the beta chain variable domain comprises a TRBV2 gene product.

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.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV12-2 gene product and the beta chain variable domain comprises a TRBV gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV9-2 gene product and the beta chain variable domain comprises a TRBV9 gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV38 gene product and the beta chain variable domain comprises a TRBV2 gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV27 gene product and the beta chain variable domain comprises a TRBV9 gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV21 gene product and the beta chain variable domain comprises a TRBV5 gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs consists essentially of TCRs comprising an alpha chain variable domain and a beta chain variable domain, wherein the alpha chain variable domain comprises a TRAV13-1 gene product and the beta chain variable domain comprises a TRBV4 gene product.

Abstract: The present invention relates to a library of particles, the library displaying a plurality of different T cell receptors (TCRs), wherein the plurality of TCRs may consist essentially of TCRs which may comprise an alpha chain variable domain from a natural repertoire and a beta chain variable domain from a natural repertoire, wherein the alpha chain variable domain may comprise a TRAV12-2 or a TRAV21 gene product and the beta chain variable domain may comprise a TRBV6 gene product.

Abstract: A T cell receptor (TCR) having the property of binding to the gp100 YLEPGPVTA peptide-HLA-A2 complex and comprising a TCR alpha variable domain and/or a TCR beta variable domain, characterized in that the domains are mutated relative to a TCR having the extracellular alpha and beta chain sequences SEQ ID NOs: 2 and that the TCR has a binding affinity for, and/or a binding half-life for, the YLEPGPVTA-HLA-A2 complex at least double that of a reference TCR. Embodiments of the invention such as the use of such TCRs in adoptive therapy, and fusions of such TCRs with therapeutic agents are also described.

Abstract: A T cell receptor (TCR) having the property of binding to the gp100 YLEPGPVTA peptide-HLA-A2 complex and comprising a TCR alpha variable domain and/or a TCR beta variable domain, characterized in that the domains are mutated relative to a TCR having the extracellular alpha and beta chain sequences SEQ ID NOs: 2 and that the TCR has a binding affinity for, and/or a binding half-life for, the YLEPGPVTA-HLA-A2 complex at least double that of a reference TCR. Embodiments of the invention such as the use of such TCRs in adoptive therapy, and fusions of such TCRs with therapeutic agents are also described.

Abstract: A T cell receptor (TCR) having the property of binding to EVDPIGHLY HLA-A1 complex and comprising a specified wild type TCR which has specific mutations in the TCR alpha variable domain and/or the TCR beta variable domain to increase affinity. Such TCRs are useful for adoptive therapy.

Abstract: The present invention provides TCRs having an affinity (KD) of less than or equal to 3 ?M, and/or an off-rate (koff) of 1×10?3 S?1 or slower, for the AAGIGILTV-HLA-A*0201 complex. Such TCRs are useful, either alone or associated with a therapeutic agent, for targeting cancer cells presenting that complex.