An Aptamer‐Functionalized DNA Circuit to Establish an Artificial Interaction between T Cells and Cancer Cells

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...

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Published inAngewandte Chemie Vol. 135; no. 39
Main Authors Wang, Zhimin, Zhang, Yue, Wu, Limei, Chen, Jianghuai, Xie, Sitao, He, Jiaxuan, Zhang, Qiang, Chen, Hong, Chen, Fengming, Liu, Yue, Zhang, Yutong, Zhuo, Yuting, Wen, Nachuan, Qiu, Liping, Tan, Weihong
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 25.09.2023
Subjects
Aptamers
Cancer
Cancer immunotherapy
Cell surface
Cell-Cell Interaction
Chemistry
Circuits
Deoxyribonucleic acid
DNA
DNA Circuit
Immunotherapy
Lymphocytes
Lymphocytes T
Receptors
T Cell Immunity
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Summary: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. An aptamer‐functionalized DNA circuit with recognition‐then‐triggering and aggregation‐then‐activation modules was designed to establish an artificial intercellular interaction mode between T cells and cancer cells. Based on cancer recognition‐induced receptor aggregation, T cells could be directly stimulated to kill target cancer cells in vitro and in vivo.
ISSN:0044-8249
1521-3757
DOI:10.1002/ange.202307656