期刊
NANO LETTERS
卷 21, 期 5, 页码 2094-2103出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.0c04783
关键词
nanoscale; artificial antigen-presenting cells; metabolic cell labeling; dendritic cells; cancer immunotherapy
类别
资金
- National Natural Science Foundation of China [81903548, 81690265, 81803444, 81521005, 32070927]
- Strategic Priority Research Program of CAS [XDA12050307]
- Youth Innovation Promotion Association of CAS [2019283]
- International Partnership Program of CAS [153631KYSB20190013]
- Shanghai Sailing Program [19YF1457300]
Metabolic labeling of DCs is utilized to design nanoscale aAPCs that exhibit enhanced distribution in lymph nodes, activation of T cells and resident APCs, significant inhibition of tumor inoculation and growth, and improved efficacy when combined with PD1 therapy.
Nanoscale artificial antigen-presenting cells (aAPCs) are promising to activate T cells directly for cancer immunotherapy, while feasible and flexible strategy to develop nanoscale aAPCs remains highly desirable. Metabolic glycoengineering is used to decorate chemical tags on cells which enables bioorthogonal chemical conjugation of functional molecules. Herein, we develop a nanoscale aAPC by metabolic dendritic cell (DC) labeling to mobilize T-cell based antitumor immunity. We coat azido-labeled DC membrane on imiquimod-loaded polymeric nanoparticles and sequentially modify anti-CD3 epsilon antibody via click chemistry. The nanoscale aAPCs perform improved distribution in lymph nodes and stimulate T cells and resident APCs. Significant inhibition of tumor inoculation and growth is observed after the vaccination, which can be further improved by combining antiprogrammed cell death receptor 1 (PD1) therapy. Our results demonstrate the promising application of metabolically labeled DCs for designing nanoscale aAPCs, which provide a simple and general strategy to potentiate cancer immunotherapy.
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