TCRs versus CARs
Adaptimmune is focused on the use of T cell therapy to treat cancer. It aims to utilise the body’s own machinery – the T cell – to target and destroy cancerous cells by using engineered, increased affinity T cell receptors (TCRs) as a means of strengthening natural patient T cell responses and overcoming tolerance to cancer. Specifically, cancerous or virally infected cells will typically present peptides of abnormal cancer proteins on their surface in association with tissue-type molecules called HLAs. This offers a “molecular fingerprint” called an epitope for T-cells from the immune system to identify. However, the majority of cancer target proteins are derived from normal proteins in the body and the T cells are naturally selected not to recognise them, manifested by having very low affinity of binding. Adaptimmune’s technology enhances the natural TCR affinity to cancer protein epitopes on the patient’s cells overcoming these obstacles for therapeutic benefit in autologous T cell therapy. One TCR therapeutic is made that can be administered to cells from multiple individual patients.
Alternative engineered T cell approaches utilise Chimeric Antibody Receptors (CARs) to modify T cells for therapeutic effect. CARs use an engineered antibody fragment to recognise the target cell and link this artificially to a number of signalling domain proteins within the T cell designed to “switch the T cell on” once the antibody recognition fragment (for example, the CD19 B cell protein) has bound to a target cell. However, although not HLA-restricted we believe CARs are limited by the low number of antibody targets available to re-direct the T cell. Adaptimmune’s approach overcomes this limitation by targeting internally processed cancer targets not thought available to antibody approaches.