%0 Journal Article
%T Engineered Norovirus-Derived Nanoparticles as a Plug-and-Play Cancer Vaccine Platform.
%A Zheng P
%A Yang Y
%A Fu Y
%A He J
%A Hu Y
%A Zheng X
%A Duan B
%A Wang M
%A Liu Q
%A Li W
%A Li D
%A Yang Y
%A Yang Z
%A Yang X
%A Huang W
%A Ma Y
%J ACS Nano
%V 17
%N 4
%D 02 2023 28
%M 36779845
%F 18.027
%R 10.1021/acsnano.2c08840
%X 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.