Synthetic immunity by remote control

Cell-based immunotherapies, such as T cells engineered with chimeric antigen receptors (CARs), have the potential to cure patients of disease otherwise refractory to conventional treatments. Early-on-treatment and long-term durability of patient responses depend critically on the ability to control the potency of adoptively transferred T cells, as overactivation can lead to complications like cytokine release syndrome, and immunosuppression can result in ineffective responses to therapy. Drugs or biologics (e.g., cytokines) that modulate immune activity are limited by mass transport barriers that reduce the local effective drug concentration, and lack site or target cell specificity that results in toxicity. Emerging technologies that enable site-targeted, remote control of key T cell functions - including proliferation, antigen-sensing, and target-cell killing - have the potential to increase treatment precision and safety profile. These technologies are broadly applicable to other immune cells to expand immune cell therapies across many cancers and diseases. In this review, we highlight the opportunities, challenges and the current state-of-the-art for remote control of synthetic immunity.