Abstract

Traditional cancer vaccines are designed to elicit tumor-specific immune responses against preexisting or recurrent tumors and have been widely explored in oncology. However, their clinical translation has been hampered by persistent limitations such as suboptimal immunogenicity, complex manufacturing processes, and safety concerns, underscoring the need for multifunctional cancer vaccines that simultaneously achieve high potency and favorable tolerability. Here, we present a tumor vaccine platform based on engineered bacterial membrane vesicles (E-MVs) displaying the well-defined tumor-associated antigen MUC1 VNTR. This platform integrates antigen delivery with the intrinsic adjuvant properties of E-MV biological macromolecule, thereby enabling both therapeutic antitumor immunity and durable prophylactic protection. E-MVs derived from engineered Escherichia coli Rosetta (DE3) exhibit a spherical morphology with a size distribution of 100-200 nm. Following subcutaneous administration, E-MVs rapidly accumulate in draining lymph nodes and are efficiently internalized by dendritic cells, promoting antigen processing and cross-presentation to T cells. Functionally, E-MVs induce significant infiltration of CD8+ T cell into the tumor microenvironment and enhance IFN-γ production, resulting in potent tumor immune responses. This leads to suppressed tumor growth, prolonged survival, and effective prevention upon tumor challenge in both "cold tumor" (breast cancer) and "hot tumor" (melanoma) mouse models. Collectively, these results demonstrate that the E-MV-based vaccine is a versatile therapeutic and prophylactic platform, offering a simple, efficient, and clinically translatable strategy to induce durable antitumor immunity.