Li et al. engineered SARS-CoV-2 B cell epitope-guided nanovaccines (BSARS) to stimulate BCR crosslinking and B cell-mediated antigen presentation, unlike most current cancer vaccines that depend on DC or macrophage antigen presentation. When compared to traditional neoantigen vaccines, BSARS neoantigen peptide or mRNA nanovaccines displayed improved efficacy in four murine tumor models. In addition to activation of a classical germinal center response, the BSARS nanovaccines increased tumor-specific follicular and non-follicular CD4+ T cells, and induced tumor-specific CD8+ T cells in a way that depended on B cell and CD4+ T cell activation.
Contributed by Ute Burkhardt
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(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.
Author Info: (1) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (2) Department of Pharmaceutical Sciences, College
Author Info: (1) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (2) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (3) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (4) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (5) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (6) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (7) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (8) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (9) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (10) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. (11) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States. Department of Pharmacology and Pharmaceutical Science, College of Pharmacy, The University of Houston, Houston, Texas 77204, United States. (12) Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48109, United States.
