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

作者：Chengyi Li, Fang Ke, Shuai Mao, Zera Montemayor, Mohamed Dit Mady Traore, Alejandro Balsa, Mahamadou Djibo, Neha Karekar, Hongxiang Hu, Hanning Wen, Wei Gao, Duxin Sun · 发表于：ACS Nano · 年份：2025 · DOI：10.1021/acsnano.4c15113 · 被引用次数：8 · 研究领域：Immunotherapy and Immune Responses、Cancer Immunotherapy and Biomarkers、T-cell and B-cell Immunology

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 SARS T NeoAg Vax) to improve anticancer efficacy by enhancing tumor-specific CD4/CD8 T cell antitumor immunity through B cell-mediated antigen presentation. B SARS T NeoAg 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 SARS T NeoAg 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.