Control of the activity of CAR-T cells within tumours via focused ultrasound.

Control of the activity of CAR-T cells within tumours via focused ultrasound.
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DOI:
10.1038/s41551-021-00779-w
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发表时间:
2021-11
影响因子:
28.1
通讯作者:
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中科院分区:
工程技术1区
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聚焦超声能够安全且无创地将能量传递到厘米深度的组织中。在此我们表明,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通过由热休克蛋白启动子控制的CAR盒在聚焦超声短脉冲产生的热量作用下被可逆地控制。在患有皮下肿瘤的小鼠中,与非诱导型CAR - T细胞的表现相比,局部注射具有诱导型CAR并通过磁共振成像引导的聚焦超声激活的T细胞减轻了靶向肿瘤外的活性,并增强了对肿瘤生长的抑制。对工程化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。
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.
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发表时间: 2013-12-11
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