Immunocore Limited

Adaptimmune Limited

Jonathan Michael Boulter

Yi Li

Bent Karsten Jakobsen

Peter Eamon Molloy

Steven Mark Dunn

Lucy Boulter, Legal Representative

Torben Bent Andersen

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.

A proteinaceous particle, for example a bacteriophage, ribosome or cell, displaying on its surface a T-cell receptor (TCR). The displayed TCR is preferably a heterodimer having a non-native disulfide bond between constant domain residues. Such display particles may be used for the creation of diverse TCR libraries for the identification of high affinity TCRs. Several high affinities are disclosed.

T cell receptor display

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.

Growing community of inventors

Abingdon, United Kingdom

Jonathan Michael Boulter