干扰素基因刺激剂
癌症研究
刺
黑色素瘤
启动(农业)
免疫系统
医学
化学
免疫学
生物
先天免疫系统
植物
发芽
工程类
航空航天工程
作者
Kaiting Yang,Wenbo Han,Xiaomin Jiang,Andras Piffko,Jason Bugno,Chuanhui Han,Sirui Li,Hua Liang,Ziwan Xu,Wenxin Zheng,Liangliang Wang,Jiaai Wang,Xiaona Huang,Jenny P.-Y. Ting,Yang–Xin Fu,Wenbin Lin,Ralph R. Weichselbaum
标识
DOI:10.1038/s41565-022-01225-x
摘要
The clinical utility of stimulator of interferon genes (STING) agonists has been limited due to poor tumour-targeting and unwanted toxicity following systemic delivery. Here we describe a robust tumour-targeted STING agonist, ZnCDA, formed by the encapsulation of bacterial-derived cyclic dimeric adenosine monophosphate (CDA) in nanoscale coordination polymers. Intravenously injected ZnCDA prolongs CDA circulation and efficiently targets tumours, mediating robust anti-tumour effects in a diverse set of preclinical cancer models at a single dose. Our findings reveal that ZnCDA enhances tumour accumulation by disrupting endothelial cells in the tumour vasculature. ZnCDA preferentially targets tumour-associated macrophages to modulate antigen processing and presentation and subsequent priming of an anti-tumour T-cell response. ZnCDA reinvigorates the anti-tumour activity of both radiotherapy and immune checkpoint inhibitors in immunologically ‘cold’ pancreatic and glioma tumour models, offering a promising combination strategy for the treatment of intractable human cancers.
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