CAR-T cells are serial killers

Abstract

Chimeric antigen receptor (CAR) T cells have enjoyed unprecedented clinical success against haematological malignancies in recent years. However, several aspects of CAR T cell biology remain unknown. We recently compared CAR and T cell receptor (TCR)-based killing in the same effector cell and showed that CAR T cells can not only efficiently kill single tumor targets, they can also kill multiple tumor targets in a sequential manner. Single and serial killing events were not sustained long term due to CAR down-regulation after 20 hours.

Keywords: CAR; T cell therapy; serial killing.

Figure 1.

CAR.OT-I T cells can mediate efficient serial killing of tumor targets bearing either CAR or TCR antigens. (A) Naive CAR.OT-I splenocytes were activated in the presence of splenic antigen presenting cells (APCs) for 3 d with 10 nmol SIINFEKL and 100 IU IL-2. CAR.OT-I T cells could effectively kill target cells expressing either MHC:SIINFEKL or HER2 tumor-associated antigen. (B) Activated CAR.OT-I T cells killed single or multiple tumor targets in a sequential fashion. The proportion of serial killer effector cells was equivalent whether they killed via the CAR (chimeric antigen receptor) or the TCR (T-cell receptor). Number indicates sequential hit and subsequent apoptosis of the target cell.