A General Biomineralization Strategy to Synthesize Autologous Cancer Vaccines with cGAS-STING Activating Capacity for Postsurgical Immunotherapy
A General Biomineralization Strategy to Synthesize Autologous Cancer Vaccines with cGAS-STING Activating Capacity for Postsurgical Immunotherapy
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DOI：
10.1021/acsnano.3c01404
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发表时间：
2023-05-15
期刊：
影响因子：
17.1
通讯作者：
Liu, Zhuang
中科院分区：
文献类型：
--
作者：
Li, Quguang;Dong, Ziliang;Liu, Zhuang
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.
