A new study published in Acta Pharmaceutica Sinica B discusses converting bacteria into an autologous tumor vaccine via surface biomineralization of calcium carbonate for enhanced immunotherapy.

Autologous cancer vaccines that stimulate tumor-specific immune responses for personalized immunotherapy hold great potential for tumor therapy. However, their efficacy is still suboptimal due to the immunosuppressive tumor microenvironment (ITM).

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The authors of this article 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.

Bacterium coating

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, this bio-vaccine achieved remarkable efficacy against both primary and metastatic tumors by eliciting potent anti-tumor immunity with full biocompatibility. This work demonstrates the potential of bioengineered bacteria as bio-active vaccines for enhanced tumor immunotherapy.