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通过聚焦超声控制肿瘤内 CAR-T 细胞的活性

英文原题:Control of the activity of CAR-T cells within tumours via focused ultrasound.

查看英文原题

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

PubMed 2021/08/12(内容时间) Nat Biomed Eng Q1 · IF 26.3(JCR 2025)

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中文摘要

聚焦超声能以安全、非侵入性的方式将能量传递至数厘米深的组织内。在此,我们表明,肿瘤内CAR-T 细胞(CAR-T 细胞)的遗传学和细胞功能可通过短脉冲聚焦超声产生的热量,经由受热休克蛋白启动子控制的CAR盒实现可逆调控。在皮下肿瘤小鼠中,与不可诱导的CAR-T 细胞相比,局部注射带有可诱导CAR的T细胞并通过磁共振成像引导的聚焦超声激活,减轻了靶向非肿瘤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。

展开英文摘要原文

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.

论文信息

作者
Wu Y、Liu Y、Huang Z、Wang X、Jin Z、Li J、Limsakul P、Zhu L
第一作者单位
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.United States
通讯作者单位
Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA. yiw015@eng.ucsd.edu.United States
文献类型
美国 NIH 资助研究
期刊
Nature biomedical engineering2021 Nov
原文标识
PubMed 34385696 · DOI 10.1038/s41551-021-00779-w