抗原
体内
免疫
体外
免疫系统
癌症研究
癌症疫苗
癌症
沙门氏菌
生物
化学
病毒学
免疫疗法
免疫学
细菌
生物化学
生物技术
遗传学
作者
Peng Zheng,Ying Yang,Yuting Fu,Ju-Liang He,Yongmao Hu,Xiao Zheng,Biao Duan,Mengzhen Wang,Qingwen Liu,Weiran Li,Duo Li,Ying Yang,Zhongqian Yang,Xu Yang,Weiwei Huang,Yanbing Ma
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-02-13
卷期号:17 (4): 3412-3429
被引量:8
标识
DOI:10.1021/acsnano.2c08840
摘要
In recent years, virus-derived self-assembled protein nanoparticles (NPs) have emerged as attractive antigen delivery platforms for developing both preventive and therapeutic vaccines. In this study, we exploited the genetically engineered Norovirus S domain (Nov-S) with SpyCatcher003 fused to the C-terminus to develop a robust, modular, and versatile NP-based carrier platform (Nov-S-Catcher003). The NPs can be conveniently armed in a plug-and-play pattern with SpyTag003-linked antigens. Nov-S-Catcher003 was efficiently expressed in Escherichia coli and self-assembled into highly uniform NPs with a purified protein yield of 97.8 mg/L. The NPs presented high stability at different maintained temperatures and after undergoing differing numbers of freeze-thaw cycles. Tumor vaccine candidates were easily obtained by modifying Nov-S-Catcher003 NPs with SpyTag003-linked tumor antigens. Nov-S-Catcher003-antigen NPs significantly promoted the maturation of bone marrow-derived dendritic cells in vitro and were capable of efficiently migrating to lymph nodes in vivo. In TC-1 and B16F10 tumor-bearing mice, the subcutaneous immunization of NPs elicited robust tumor-specific T-cell immunity, reshaped the tumor microenvironment, and inhibited tumor growth. In the TC-1 model, the NPs even completely abolished established tumors. In conclusion, the Nov-S-Catcher003 system is a promising delivery platform for facilitating the development of NP-based cancer vaccines.
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