Tumor-Targeted Bacterial Vaccine Induces In Situ Immunogenic Cell Death for Cancer Immunotherapy.

Abstract

The immunosuppressive nature and low antigenicity of solid tumors present major obstacles for effective cancer vaccination. Here, we report a live bacteria-based vaccine platform engineered by coating attenuated <i>Salmonella</i> (<i>SAL</i>) with a cancer cell membrane (CCM), integrating pathogenic adjuvants and autologous tumor antigens into a single entity. This CCM@<i>SAL</i> system leverages bacterial immunogenicity to induce immunogenic cell death (ICD) within the tumor microenvironment, promoting in situ release of endogenous antigens and damage-associated molecular patterns. These events synergize to prime antigen-presenting cells and activate tumor-specific T cells. Notably, CCM coating reduces bacterial clearance by phagocytes and enhances tumor accumulation. The combination of ICD induction and tumor-targeted antigen delivery enables a self-amplifying vaccination cycle within the tumor. This in situ vaccination induces durable systemic immunity and suppresses tumor progression in multiple murine models. By integrating tumor targeting, ICD induction, and antigen presentation, CCM@<i>SAL</i> offers a broadly applicable strategy to improve cancer vaccine efficacy.