Intracellular Bacteria-Mimicking Whole-Cell Cancer Vaccine Potentiates Immune Responses via Concurrent Activation of NLRP3 Inflammasome and STING Pathway.

Abstract

Whole-cell cancer vaccines can trigger broader-spectrum antitumoral immune responses. However, a lack of immunogenicity and unclear interactions with antigen-presenting cells (APCs) hinder their translation into effective personalized immunotherapies. Herein, tumor cells are engineered via layer-by-layer bimineralization integrating sequential silicification and manganese mineralization, which reprograms the APC recognition with high immunogenicity. These bacteria-mimicking cells with enhanced mechanical stiffness protect against antigen degradation and facilitate phagocytosis by APCs. The secondary Mn mineralization creates spiky-like MnO₂ nanoclusters with extreme roughness that stimulate the intracellular NLRP3 inflammasome and concurrently activate the cGAS-STING pathway, which is closely related to diverse immune patterns in response to intracellular bacterial infection. As a consequence, such bimineralized tumor cells outperform other monomineralized vaccinations in terms of prophylactic and therapeutic outcomes against the development and progression of a mouse B16F10 melanoma model. This bimineralization strategy uniquely bridges materials science and immunology, offering a transformative framework for engineering immunogenic whole-cell cancer vaccines.