The first step is to identify and validate a T-cell clone specific for the desired epitope; this can either be generated in- house or in-licensed, as appropriate. The T-Cell Receptor (TCR) from the clone is then isolated and re-engineered into a soluble format through the introduction of a new inter-chain disulphide bond that is buried within the core of the TCR, leaving the TCR’s external surfaces completely native. This stabilised protein is truncated at the transmembrane domains to generate a soluble, low-affinity (micromolar) mTCR.

Like antibodies, TCRs contain 6 hypervariable complementary determining regions (CDRs) which form the binding epitope contact surface. Immunocore engineers these CDR regions to increase the affinity of the mTCR for its target while maintaining specificity, typically resulting in mTCRs with low pM affinities and long target residence times. Read more »

The final step is to generate and validate fusions to the desired effector function. The mTCR is linked to the effector, an anti-CD3 scFv. This mediates T cell redirection and is a clinically-validated, highly potent therapeutic mechanism of action.  Read more »