Adoptive T‐cell therapy: adverse events and safety switches

The potential of adoptive T‐cell therapy in effecting complete and durable responses has been demonstrated in a number of malignant and infectious diseases. Ongoing progress in T‐cell engineering has given cause for optimism in the broader clinical applicability of this approach. However, the development of more potent T cells is checked by safety concerns, highlighted by the occurrence of on‐target and off‐target toxicities that, although uncommon, have been fatal on occasions. Timely pharmacological intervention is effective in the management of a majority of adverse events but adoptively transferred T cells can persist long term, along with any unwanted effects. A recently validated cellular safety switch, inducible caspase 9 (iCasp9), has the potential to mitigate the risks of T‐cell therapy by enabling the elimination of transferred T cells if required. In haematopoietic stem cell transplantation, iCasp9‐modified donor T cells can be rapidly eliminated in the event of graft‐versus‐host disease. This review presents an overview of the risks associated with modern T‐cell therapy and the development, clinical results and potential future application of the iCasp9 safety switch.