Remote control of cellular immunotherapy

Chimeric antigen receptor (CAR) T cell immunotherapy is emerging as a powerful tool for cancer treatment. However, the clinical application of CAR T cell therapy remains limited owing to on-target off-tumour toxicity and cytokine release syndrome, which can cause severe side effects. Remote and spatiotemporal control of CAR T cells could improve the safety and efficacy of CAR T cell therapy. Here, we discuss how CAR T cells can be externally controlled by combining stimuli-responsive nanotechnologies with immuno-engineering. We examine the use of different external stimuli, including light, ultrasound, magnetic fields, X-rays, electric fields and small molecules, to control the activity of CAR T cells against different malignancies and highlight the need for more efficient and biocompatible external stimuli as well as issues to be addressed to effectively treat solid tumours with CAR T cell therapy. Chimeric antigen receptor (CAR) T cell activities can be remotely controlled to provide spatiotemporal precision of CAR T cell activity and improve the safety of cellular immunotherapies. This Review discusses physical and chemogenetic stimuli and the combination of stimuli-responsive nanotechnologies with immuno-engineering to design controllable CAR T cell therapies.