Focused ultrasound can deliver energy safely and non-invasively into tissues at depths of centimetres. Here we show that the genetics and cellular functions of chimeric antigen receptor T cells (CAR-T cells) within tumours can be reversibly controlled by the heat generated by short pulses of focused ultrasound via a CAR cassette under the control of a promoter for the heat-shock protein. In mice with subcutaneous tumours, locally injected T cells with the inducible CAR and activated via focused ultrasound guided by magnetic resonance imaging mitigated on-target off-tumour activity and enhanced the suppression of tumour growth, compared with the performance of non-inducible CAR-T cells. Acoustogenetic control of the activation of engineered T cells may facilitate the design of safer cell therapies.

聚焦超声可以安全、无创地将能量传递到厘米深度的组织中。在这里，我们展示了肿瘤内嵌合抗原受体 T 细胞（CAR-T 细胞）的遗传学和细胞功能可以通过在热启动子控制下的 CAR 盒通过聚焦超声短脉冲产生的热量可逆地控制-休克蛋白。在患有皮下肿瘤的小鼠中，与非诱导型 CAR 相比，局部注射具有诱导型 CAR 的 T 细胞并通过由磁共振成像引导的聚焦超声激活可减轻靶外肿瘤活动并增强对肿瘤生长的抑制。 T细胞。工程化 T 细胞活化的声遗传学控制可能有助于设计更安全的细胞疗法。