A General Biomineralization Strategy to Synthesize Autologous Cancer Vaccines with cGAS-STING Activating Capacity for Postsurgical Immunotherapy

Autologous cancer vaccines constructed by nonproliferativewholetumor cells or tumor lysates together with appropriate adjuvants representa promising strategy to suppress postsurgical tumor recurrence. Inspiredby the potency of cytosolic double-stranded DNA (dsDNA) in initiatinganticancer immunity by activating the cyclic GMP-AMP synthase-stimulatorof interferon genes (cGAS-STING) pathway, we herein report the concisesynthesis of a cGAS-STING agonist through dsDNA-templated biomineralizationgrowth of calcium carbonate (CaCO3) microparticles. Theyielded DNA@CaCO3 can activate the intracellular cGAS-STINGpathway of dendritic cells (DCs) by promoting endosomal escape ofdsDNA, triggering their maturation and activation as a potent immunestimulator. Upon intratumoral injection, DNA@CaCO3 canreverse the immunosuppressive tumor microenvironment by simultaneouslyprovoking innate and adaptive antitumor immunity, thereby effectivelysuppressing the growth of murine CT26 and B16-F10 tumors inmice. Furthermore, via CaCO3-based biomineralization ofcomplete tumor lysates, we constructed a personalized autologous cancervaccine with intrinsic cGAS-STING activation capacity that could provoketumor-specific immune responses to not only delay the growth of challengedtumors but also synergize with anti-PD-1 immunotherapy to suppresspostsurgical tumor recurrence. This study highlights a CaCO3-based biomineralization method to prepare autologous cancer vaccinesin a concise manner, which is promising for personalized immunotherapyand clinical translation.

Automated summary

By activating the cGAS-STING pathway using cytosolic double-stranded DNA, a cGAS-STING agonist was synthesized through dsDNA-templated biomineralization growth. The resulting DNA@CaCO3 can activate dendritic cells and promote immune stimulation. Additionally, personalized autologous cancer vaccines were constructed using complete tumor lysates and CaCO3-based biomineralization, leading to tumor-specific immune responses.