Immunocore Limited

Adaptimmune Limited

Steven Mark Dunn

Yi Li

Bent Karsten Jakobsen

Peter Eamon Molloy

Jonathan Michael Boulter

Lucy Boulter, Legal Representative

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC SEQ ID NO:126 peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a Kfor the said peptide-HLA complex of less than or equal to 1 &#x3bc;M and/or have an off-rate (k) of 1&#xd7;10Sor slower.

High affinity NY-ESO T cell receptors

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC SEQ ID NO:126 peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumor cells. The TCRs have a Kfor the said peptide-HLA complex of less than or equal to 1 &#x3bc;M and/or have an off-rate (k) of 1&#xd7;10Sor slower.

The present invention provides TCRs having high affinity. The TCR binds to SLYNTVATL (SEQ ID NO:16)-HLA-A*0201 with a Kof less than or equal to 1 &#x3bc;M and/or an off-rate (k) of 1&#xd7;10Sor slower using Surface Plasmon Resonance. The TCRs are non-native, isolated or recombinant. The TCRs are useful, either alone, or with a therapeutic agent, for targeting HIV infected cells that present the SLYNTVATL (SEQ ID NO:16)-HLA-A*0201 complex.

High affinity HIV T cell receptors

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC (SEQ ID NO:126) peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a Kfor the said peptide-HLA complex of less than or equal to 1 &#x3bc;M and/or have an off-rate (k) of 1&#xd7;10Sor slower.

High affinity NY-ESO T cell receptor

The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC (SEQ ID NO:126)-HLA-A*0201, the SLLMWITQC (SEQ ID NO:126) peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumor cells. The TCRs have a Kfor the said that peptide-HLA complex of less than or equal to 1 &#x3bc;M and/or have an off-rate (k) of 1&#xd7;10Sor slower.

A method of increasing the affinity and/or decreasing the off-rate of a given TCR specific for a given target pMHC, comprising creating a plurality of TCRs having an &#x3b1; chain CDR2 sequence and/or a &#x3b2; chain CDR2 sequence different from the corresponding CDR2 sequence(s) of the given TCR but having the same &#x3b1; and &#x3b2; CDR1 and CDR3 sequences as the given TCR, determining the affinity and/or off-rate of members of said plurality of TCRs for the target pMHC, and selecting one or more members having at least a 10-fold greater affinity for the target pMHC than the given TCR and/or a 10-fold slower off-rate for the target pMHC than the given TCR.

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Abingdon, United Kingdom

Steven Mark Dunn