CAR-T（CAR-T）细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CAR-T（CAR-T）细胞在血液系统恶性肿瘤中的应用推动了这种免疫治疗形式的显著进展。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
超声可控且不依赖抗原的顺式激活 CAR-T 细胞杀伤
英文原题：Ultrasound controllable and antigen-independent killing via cis-activating CAR T cells.
查看英文原题
Ultrasound controllable and antigen-independent killing via cis-activating CAR T cells.
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中文摘要
嵌合抗原受体（CAR）T细胞疗法的临床疗效受到肿瘤抗原逃逸和异质性的限制，导致癌症复发。为解决这一局限性，我们开发了一种聚焦超声（FUS）可控且顺式激活的CAR（FUS-CisCAR）平台，其中CAR-T 细胞被工程化改造为在FUS刺激下表达其自身的靶抗原。这种自供抗原触发了一个顺式激活环路，启动局部旁观者效应以清除附近的肿瘤细胞，包括那些缺乏靶抗原的肿瘤细胞。我们证明，原代人FUS-CisCAR T细胞在体外和体内模型中均能有效杀伤局部抗原阴性肿瘤细胞。FUS-CisCAR平台提供了一种可控策略，有望克服由肿瘤异质性和抗原逃逸引起的复发，从而增强CAR-T 细胞疗法的持久性。
展开英文摘要原文
Clinical efficacy of chimeric antigen receptor (CAR) T cell therapy is limited by tumor antigen escape and heterogeneity, leading to cancer relapse. To address this limitation, we developed a focused ultrasound (FUS) controllable and cis -activated CAR (FUS-CisCAR) platform, in which CAR T cells are engineered to express their own target antigen upon FUS stimulation. This self-supplied antigen triggers a " cis -activation" loop, initiating a localized bystander effect to eliminate nearby tumor cells, including those that lack the target antigen.
We demonstrate that primary human FUS-CisCAR T cells effectively kill local antigen-negative tumor cells in both in vitro and in vivo models. The FUS-CisCAR platform offers a controllable strategy that has the potential to overcome relapse caused by tumor heterogeneity and antigen escape, thus enhancing the durability of CAR T cell therapy.
论文信息
- 作者
- Zhu L、Cui J、Man CW、Mouchawar A、Yu X、Huang Y、Wu Y、Guo T
- 单位
- Alfred E. Mann Department of Biomedical Engineering, University of Southern California, Los Angeles, Los Angeles, CA 90089, USA.United States
- 期刊
- Molecular therapy. Oncology2026 Sep 17
- 原文标识
- PubMed 42698668 · DOI 10.1016/j.omton.2026.201323
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