重编程
适体
免疫疗法
癌症研究
癌症免疫疗法
计算生物学
肿瘤细胞
化学
计算机科学
细胞生物学
细胞
生物
生物化学
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,Huajun 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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