Autologous
cancer vaccine that stimulates
tumor-specific immune responses for personalized
immunotherapy holds great potential for
tumor therapy. However, its efficacy is still suboptimal due to the immunosuppressive tumor microenvironment (ITM). Here, we report a new type of bacteria-based autologous
cancer vaccine by employing
calcium carbonate (CaCO3) biomineralized Salmonella (Sal) as an in-situ
cancer vaccine producer and systematical ITM regulator. CaCO3 can be facilely coated on the Sal surface with
calcium ionophore A23187 co-loading, and such biomineralization did not affect the bioactivities of the bacteria. Upon intratumoral accumulation, the CaCO3 shell was decomposed at an acidic microenvironment to attenuate
tumor acidity, accompanied by the release of Sal and Ca2+/
A23187. Specifically, Sal served as a
cancer vaccine producer by inducing
cancer cells' immunogenic cell death (ICD) and promoting the gap junction formation between
tumor cells and dendritic cells (DCs) to promote antigen presentation. Ca2+, on the other hand, was internalized into various types of immune cells with the aid of
A23187 and synergized with Sal to systematically regulate the immune system, including DCs maturation, macrophages polarization, and T cells activation. As a result, such bio-
vaccine achieved remarkable efficacy against both primary and metastatic
tumors by eliciting potent anti-
tumor immunity with full biocompatibility. This work demonstrated the potential of bioengineered bacteria as bio-active
vaccines for enhanced
tumor immunotherapy.