Coating with flexible DNA network enhanced T-cell activation and tumor killing for adoptive cell therapy

Acta Pharmaceutica Sinica B

卷:11

Yuanqing Zhang¹  Qiaojuan Liu²  Minhao Wu³  Ziyan Zhang⁴  Ting Liu⁵  Xiaoxia Zhan⁵  Yuting Wang⁵  Gen Lu⁶  Jizhou Tan⁶ 

[1] Corresponding authors.;

[2] National and Local United Engineering Lab of Druggability and New Drugs Evaluation, Sun Yat-sen University, Guangzhou 510006, China;

[3] Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou 510080, China;

[4] School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China;

[5] The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China;

[6] Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China;

关键词: Cell surface engineering;    Selective cytoprotection;    DNA nanostructure;    Tetrahedral DNA nanostructure;    Rolling circle amplification;    Adoptive cell therapy;   

DOI  :  

来源: DOAJ

【 摘 要 】

Adoptive cell therapy (ACT) is an emerging powerful cancer immunotherapy, which includes a complex process of genetic modification, stimulation and expansion. During these in vitro or ex vivo manipulation, sensitive cells are inescapability subjected to harmful external stimuli. Although a variety of cytoprotection strategies have been developed, their application on ACT remains challenging. Herein, a DNA network is constructed on cell surface by rolling circle amplification (RCA), and T cell-targeted trivalent tetrahedral DNA nanostructure is used as a rigid scaffold to achieve high-efficient and selective coating for T cells. The cytoprotective DNA network on T-cell surface makes them aggregate over time to form cell clusters, which exhibit more resistance to external stimuli and enhanced activities in human peripheral blood mononuclear cells and liver cancer organoid killing model. Overall, this work provides a novel strategy for in vitro T cell-selective protection, which has a great potential for application in ACT.

【 授权许可】

Unknown