通过聚焦超声控制肿瘤内 CAR-T 细胞的活性。
Control of the activity of CAR-T cells within tumours via focused ultrasound.
机构信息
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA, USA.
出版信息
Nat Biomed Eng. 2021 Nov;5(11):1336-1347. doi: 10.1038/s41551-021-00779-w. Epub 2021 Aug 12.
Abstract
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.
摘要
聚焦超声可以将能量安全、非侵入性地传递到几厘米深的组织中。在这里，我们通过热休克蛋白启动子控制下的嵌合抗原受体（CAR）盒，展示了肿瘤内嵌合抗原受体 T 细胞（CAR-T 细胞）的遗传和细胞功能可以通过短脉冲聚焦超声产生的热量来可逆地控制。在皮下肿瘤的小鼠中，通过磁共振成像引导的聚焦超声激活的局部注射的诱导型 CAR-T 细胞减轻了针对肿瘤的脱靶活性，并增强了对肿瘤生长的抑制作用，与非诱导型 CAR-T 细胞的性能相比。工程 T 细胞激活的声遗传学控制可能有助于设计更安全的细胞疗法。
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