DNA Engineered Lymphocyte-Based Homologous Targeting Artificial Antigen-Presenting Cells for Personalized Cancer Immunotherapy
Lele Sun1,#, Fengyun Shen1,#, Zijian Xiong1, He Yang1, Ziliang Dong1, Jian Xiang2, Qingyang Gu2, Qunsheng Ji2, Chunhai Fan3, Zhuang Liu1,*
1Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nanoscience and Technology, Soochow University, 199 Ren-AiRoad, Suzhou 215123, China.
2WuXi AppTec (Suzhou) Co., Ltd., Suzhou 215104, Jiangsu
3Natl Ctr Translat Med, Frontiers Sci Ctr Transformat Mol, Sch Chem & Chem Engn, Shanghai Jiao Tong University, Shanghai 200240, China
Artificial antigen-presenting cells (aAPCs) constructed by integrating T cell activation ligands on biocompatible materials hold great potential in tumor immunotherapy. However, it remains challenging to develop aAPCs, which could mimic the characteristics of natural APCs, thereby realizing antigen-specific T cells activation in vivo. Here, we report the first effort to construct natural lymphocyte-based homologous targeting aAPCs (LC-aAPCs) with lipid-DNA-mediated noninvasive live cell surface engineering. Through a predesigned bottom-up self-assembly path, we achieved natural-APC-mimicking distribution of T cell activation ligands on LC-aAPCs, which would enable the optimized T cell activation. Moreover, the lipid-DNA-mediated self-assembly occurring on lipid bilayers would not affect the functions of homing receptors expressed on lymphocyte. Therefore, such LC-aAPCs could actively migrate to peripheral lymphatic organs and then effectively activate antigen-specific T cells. Combined with an immune checkpoint inhibitor, such LC-aAPCs could effectively inhibit the growth of different tumor models. Thus, our work provides a new design of aAPCs for in vivo applications in tumor immunotherapy, and the lipid-DNA-mediated noninvasive live cell surface engineering would be a powerful tool for designing cell-based therapeutics.