重编程
适体
嵌合抗原受体
免疫疗法
贪婪
抗原
细胞毒性T细胞
癌症研究
癌症免疫疗法
计算生物学
T细胞
体外
细胞生物学
细胞
生物
免疫学
免疫系统
癌症
分子生物学
遗传学
作者
Qiang Zhang,Limei Wu,Yue Zhang,Dan Wang,Yingyu Sima,Zhimin Wang,Zhiwei Yin,Hui Wu,Yuting Zhuo,Yutong Zhang,Linlin Wang,Yong Chen,Yanlan Liu,Liping Qiu,Weihong Tan
出处
期刊:ACS central science
[American Chemical Society]
日期:2024-03-21
标识
DOI:10.1021/acscentsci.3c01511
摘要
Innovating the design of chimeric antigen receptors (CARs) beyond conventional structures would be necessary to address the challenges of efficacy, safety, and applicability in T cell-based cancer therapy, whereas excessive genetic modification might complicate CAR design and manufacturing, and increase gene editing risks. In this work, we used aptamers as the antigen-recognition unit to develop a nongenetic CAR engineering strategy for programming the antitumor activity and specificity of CAR T cells. Our results demonstrated that aptamer-functionalized CAR (Apt-CAR) T cells could be directly activated by recognizing target antigens on cancer cells, and then impart a cytotoxic effect for cancer elimination in vitro and in vivo. The designable antigen recognition capability of Apt-CAR T cells allows for easy modulation of their efficacy and specificity. Additionally, multiple features, e.g., tunable antigen-binding avidity and the tumor microenvironment responsiveness, could be readily integrated into Apt-CAR design without T cell re-engineering, offering a new paradigm for developing adaptable immunotherapeutics.
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