Programming a serial killer: CAR T cells form non-classical immune synapses

Chimeric Antigen Receptors (CARs) are engineered immune receptors that underpin a promising new form of cellular immunotherapy for the treatment of cancer. Recently there have been two landmark FDA approvals for the use of Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies, and with more than 300 CAR T cell clinical trials globally, it has become more important than ever to investigate the cell biology of these new “living” immunotherapies. The rapid pace at which these therapies have been translated, means that we still have a way to go in understanding how triggering T cells via a synthetic engineered receptor might alter the cell biology, function and persistence of CAR T cells. We have previously shown that CAR T cells have the ability to be serial killers, a property likely to be a key requirement for effective anti-tumour therapy and ultimately influencing the numbers of CAR T cells required for effective therapy [1]