Recent synthetic biology advancements have shown that cells can be engineered to respond to external stimuli such as chemical compounds and light, which significantly improves the specificity and controllability of CAR T therapy. However, the lack of both spatiotemporal and depth control is still the main issue in the clinic of CAR T treatment. At the same time, mechanogenetics, capable of penetrating deep tissues with high spatiotemporal precision, is rapidly evolving and advancing to reveal its potential for cancer immunotherapy. In the past few years, researchers have demonstrated the precise and remote control of engineered cells with mechanical perturbation originated from ultrasound, which may become a new solution to circumvent the limitations of CAR T therapy in the future. This review will discuss mechanobiology and the state-of art designs of controllable CAR T cells. A specific focus of this review will be on the mechanical control of CAR T therapy.
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