Molecular Science and Biomedicine Laboratory (MBL), State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Aptamer Engineering Center of Hunan Province, Hunan University, Changsha, Hunan 410082, China.
The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
Angew Chem Int Ed Engl. 2023 Sep 25;62(39):e202307656. doi: 10.1002/anie.202307656. Epub 2023 Aug 17.
Nongenetic strategies that enable control over the cell-cell interaction network would be highly desired, particularly in T cell-based cancer immunotherapy. In this work, we developed an aptamer-functionalized DNA circuit to modulate the interaction between T cells and cancer cells. This DNA circuit was composed of recognition-then-triggering and aggregation-then-activation modules. Upon recognizing target cancer cells, the triggering strand was released to induce aggregation of immune receptors on the T cell surface, leading to an enhancement of T cell activity for effective cancer eradication. Our results demonstrated the feasibility of this DNA circuit for promoting target cancer cell-directed stimulation of T cells, which, consequently, enhanced their killing effect on cancer cells. This DNA circuit, as a modular strategy to modulate intercellular interactions, could lead to a new paradigm for the development of nongenetic T cell-based immunotherapy.
非常希望有一种非遗传策略能够控制细胞间相互作用网络，特别是在基于 T 细胞的癌症免疫疗法中。在这项工作中，我们开发了一种适配子功能化的 DNA 电路来调节 T 细胞与癌细胞之间的相互作用。这个 DNA 电路由识别-触发和聚集-激活模块组成。在识别靶癌细胞后，触发链被释放以诱导 T 细胞表面免疫受体的聚集，从而增强 T 细胞的活性，以有效清除癌细胞。我们的结果证明了这种 DNA 电路促进靶癌细胞定向刺激 T 细胞的可行性，从而增强了它们对癌细胞的杀伤效果。作为一种调节细胞间相互作用的模块化策略，这种 DNA 电路可能为开发非遗传的基于 T 细胞的免疫疗法带来新的范例。
