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 engineers the natural TCR affinity to cancer protein epitopes on the patient’s cells in order to target and then destroy cancer cells in patients.  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.  Unlike CARs our TCR therapeutics can target both intracellular as well as extracellular cancer target proteins. This capability significantly increases the breadth of targets.Illus 2