SARS-CoV-2 B Epitope-Guided Neoantigen NanoVaccines Enhance Tumor-Specific CD4/CD8 T Cell Immunity through B Cell Antigen Presentation.

Li, Chengyi; Ke, Fang; Mao, Shuai; Montemayor, Zera; Traore, Mohamed Dit Mady; Balsa, Alejandra Duran; Djibo, Mahamadou; Karekar, Neha et al. · ACS Nano · 2025

basic_science · Level V

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Abstract

Current neoantigen cancer vaccines activate T cell immunity through dendritic cell/macrophage-mediated antigen presentation. It is unclear whether incorporating B cell-mediated antigen presentation into current neoantigen vaccines could enhance CD4/CD8 T cell immunity to improve their anticancer efficacy. We developed SARS-CoV-2 B cell epitope-guided neoantigen peptide/mRNA cancer nanovaccines (B<sub>SARS</sub>T<sub>NeoAg</sub>Vax) to improve anticancer efficacy by enhancing tumor-specific CD4/CD8 T cell antitumor immunity through B cell-mediated antigen presentation. B<sub>SARS</sub>T<sub>NeoAg</sub>Vax cross-linked with B cell receptor, promoted SARS-CoV-2 B cell-mediated antigen presentation to tumor-specific CD4 T cells, increased tumor-specific follicular/nonfollicular CD4 T cells, and enhanced B cell-dependent tumor-specific CD8 T cell immunity. B<sub>SARS</sub>T<sub>NeoAg</sub>Vax achieved superior efficacy in melanoma, pancreatic, and breast cancer models compared with the current neoantigen vaccines. Our study provides a universal platform, SARS-CoV-2 B epitope-guided neoantigen nanovaccines, to improve anticancer efficacy against various cancer types by enhancing CD4/CD8 T cell antitumor immunity through viral-specific B cell-mediated antigen presentation.

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