肿瘤微环境
免疫检查点
癌症研究
脚手架
活性氧
封锁
吉西他滨
化学
免疫系统
PD-L1
医学
细胞生物学
免疫疗法
癌症
受体
生物
免疫学
生物化学
内科学
肿瘤细胞
生物医学工程
作者
Chao Wang,Jinqiang Wang,Xudong Zhang,Shuangjiang Yu,Di Wen,Quanyin Hu,Yanqi Ye,Hunter N. Bomba,Xiuli Hu,Zhuang Liu,Gianpietro Dotti,Zhen Gu
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2018-02-21
卷期号:10 (429)
被引量:435
标识
DOI:10.1126/scitranslmed.aan3682
摘要
Patients with low-immunogenic tumors respond poorly to immune checkpoint blockade (ICB) targeting the programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway. Conversely, patients responding to ICB can experience various side effects. We have thus engineered a therapeutic scaffold that, when formed in situ, allows the local release of gemcitabine (GEM) and an anti-PD-L1 blocking antibody (aPDL1) with distinct release kinetics. The scaffold consists of reactive oxygen species (ROS)-degradable hydrogel that releases therapeutics in a programmed manner within the tumor microenvironment (TME), which contains abundant ROS. We found that the aPDL1-GEM scaffold elicits an immunogenic tumor phenotype and promotes an immune-mediated tumor regression in the tumor-bearing mice, with prevention of tumor recurrence after primary resection.
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