干扰素基因刺激剂
刺
癌症免疫疗法
免疫疗法
癌症研究
免疫系统
肿瘤微环境
先天免疫系统
癌症
医学
生物
免疫学
内科学
工程类
航空航天工程
作者
Quguang Li,Ziliang Dong,Zhiqin Cao,Huali Lei,Chunjie Wang,Hao Yu,Liangzhu Feng,Zhuang Liu
出处
期刊:ACS Nano
[American Chemical Society]
日期:2023-05-15
卷期号:17 (11): 10496-10510
被引量:16
标识
DOI:10.1021/acsnano.3c01404
摘要
Autologous cancer vaccines constructed by nonproliferative whole tumor cells or tumor lysates together with appropriate adjuvants represent a promising strategy to suppress postsurgical tumor recurrence. Inspired by the potency of cytosolic double-stranded DNA (dsDNA) in initiating anticancer immunity by activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, we herein report the concise synthesis of a cGAS-STING agonist through dsDNA-templated biomineralization growth of calcium carbonate (CaCO3) microparticles. The yielded DNA@CaCO3 can activate the intracellular cGAS-STING pathway of dendritic cells (DCs) by promoting endosomal escape of dsDNA, triggering their maturation and activation as a potent immune stimulator. Upon intratumoral injection, DNA@CaCO3 can reverse the immunosuppressive tumor microenvironment by simultaneously provoking innate and adaptive antitumor immunity, thereby effectively suppressing the growth of murine CT26 and B16-F10 tumors in mice. Furthermore, via CaCO3-based biomineralization of complete tumor lysates, we constructed a personalized autologous cancer vaccine with intrinsic cGAS-STING activation capacity that could provoke tumor-specific immune responses to not only delay the growth of challenged tumors but also synergize with anti-PD-1 immunotherapy to suppress postsurgical tumor recurrence. This study highlights a CaCO3-based biomineralization method to prepare autologous cancer vaccines in a concise manner, which is promising for personalized immunotherapy and clinical translation.
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