FlaB-expressing bacterial uter membrane vesicles vaccine mediating anti-tumor immune response via promoting DCs activation and lymph nodes-homing

Cancer vaccine efficacy relies on T cells eliciting tumor-specific adaptive immunity, with antigen-presenting cells, particularly dendritic cells (DCs), playing a crucial role. After capturing antigens, DCs migrate to lymph nodes, where they present antigens to naïve T cells and activate B and natural killer (NK) cells, thereby strengthening anti-tumor immune responses. However, limitations in immune adjuvants and insufficient antigen presentation hinder DCs migration, reducing vaccine effectiveness. This study introduces an outer membrane vesicle (OMV)-based platform engineered to express Vibrio vulnificus flagellin B (FlaB), a Toll-like receptor 5 (TLR5) agonist. FlaB effectively activates DCs, enhances interactions with T cells, provides robust costimulatory signals, and promotes cytotoxic CD8⁺ T cell differentiation. Compared to unmodified OMV-Ag, the antigen-loaded OMV-FlaB-Ag nanovaccine significantly enhances DC function, eliciting potent antitumor responses and delaying tumor progression across multiple models. When combined with immune checkpoint inhibitors, it further amplifies antitumor immunity, markedly suppressing tumor growth and improving therapeutic outcomes.