{Reference Type}: Journal Article
{Title}: Engineered Norovirus-Derived Nanoparticles as a Plug-and-Play Cancer Vaccine Platform.
{Author}: Zheng P;Yang Y;Fu Y;He J;Hu Y;Zheng X;Duan B;Wang M;Liu Q;Li W;Li D;Yang Y;Yang Z;Yang X;Huang W;Ma Y;
{Journal}: ACS Nano
{Volume}: 17
{Issue}: 4
{Year}: 02 2023 28
{Factor}: 18.027
{DOI}: 10.1021/acsnano.2c08840
{Abstract}: 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.