The rationale behind the development of the mTCR platform is to target cells that cannot be reached by conventional monoclonal antibodies – while monoclonal antibodies have revolutionised the treatment of a range of diseases, their continued expansion is severely limited by the lack of new protein targets.  This is because antibodies are designed to target cellular surface proteins, which represent only a small percentage of known disease-relevant targets.  The majority of disease-relevant proteins are either secreted (i.e. released from the cell) or remain within the cell (Intracellular proteins): neither of which allow the cell to be targeted by monoclonal antibodies.  The body, however, has a second mechanism by which the immune system can scan cells for intracellular alterations such as those found in cancer or viral infection. This mechanism is known as the HLA-TCR recognition system.

In this system each cell actively presents small peptide epitopes derived from all of its proteins at the cell surface via Human Leukocyte Antigen (HLA) proteins. Passing T-cells then scan these presented peptides using T-Cell Receptors (TCRs) looking for non-self derived epitopes. Like antibodies, these TCRs are extremely specific for an individual epitope, allowing them to be successfully used to target cells expressing a disease-related protein of interest.

Immunocore’s core technology enables the engineering of disease specific TCRs into soluble, high-affinity variants that actively target the desired cells in vivo as a means to deliver potent therapeutics in a targeted manner.  These TCRs are called monoclonal TCRs or mTCRs.