Abstract 3545: Enhancing anticancer immunity with SARS-CoV-2 B cell epitope-guided neoantigen nanovaccines

Abstract Background: Current neoantigen cancer vaccines primarily rely on dendritic cell- and macrophage-mediated antigen presentation to activate T cell immunity. However, the potential of incorporating B cell-mediated antigen presentation into these vaccines to enhance CD4 and CD8 T cell responses has not been fully explored. Methods: We developed BSARSTNeoAgVax, a SARS-CoV-2 B cell epitope-guided neoantigen peptide or mRNA cancer nanovaccine, designed to leverage B cell-mediated antigen presentation. BSARSTNeoAgVax was tested in three mouse cancer models (melanoma, pancreatic cancer, and breast cancer) using two types of T cell tumor neoantigens (peptide or mRNA) and two types of nano delivery systems (I or lipid nanoparticles, LNP). SARS-CoV-2 B cell epitopes were conjugated on the surface of I or LNP to facilitate crosslinking with the B cell receptor (BCR) on SARS-CoV-2-specific B. Immune responses and therapeutic efficacy of BSARSTNeoAgVax were compared with existing neoantigen vaccines. Results: BSARSTNeoAgVax enabled SARS-CoV-2 B cell-mediated antigen presentation to tumor-specific CD4 T cells, significantly enhancing the activation of tumor-specific follicular and non-follicular CD4 T cells. This interaction also promoted B cell-dependent tumor-specific CD8 T cell immunity, resulting in robust antitumor responses. Importantly, the efficacy of BSARSTNeoAgVax was independent of antibody production, as the SARS-CoV-2 B cell epitopes on the vaccine generated anti-SARS-CoV-2 antibodies that lacked anticancer efficacy. In the mouse cancer models, BSARSTNeoAgVax demonstrated superior efficacy, showing improved tumor control and enhanced immune activation compared to current neoantigen vaccines. Conclusion: Our findings establish a universal platform for cancer immunotherapy, utilizing SARS-CoV-2 B epitope-guided neoantigen nanovaccines to enhance CD4 and CD8 T cell antitumor immunity through viral-specific B cell-mediated antigen presentation. This approach holds significant promise for improving the efficacy of neoantigen-based cancer vaccines across diverse tumor types. Citation Format: Chengyi Li, Fang Ke, Shuai Mao, Zera Montemayor, Mohamed Dit Mady Traore, Alejandra Duran Balsa, Mahamadou Djibo, Neha Karekar, Hanning Wen, Wei Gao, Duxin Sun. Enhancing anticancer immunity with SARS-CoV-2 B cell epitope-guided neoantigen nanovaccines [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3545.