免疫系统
不利影响
免疫疗法
免疫检查点
癌症研究
癌症免疫疗法
间充质干细胞
癌症
医学
药理学
免疫学
内科学
病理
作者
Shufang Shen,Huaxing Dai,Ziying Fei,Yu Shuang Chai,Hao Yu,Qin Fan,Ziliang Dong,Yujie Zhu,Jialu Xu,Qingle Ma,Xiao Han,Ligeng Xu,Fei Peng,Zhuang Liu,Chao Wang
出处
期刊:ACS Nano
[American Chemical Society]
日期:2021-05-14
卷期号:15 (5): 9111-9125
被引量:27
标识
DOI:10.1021/acsnano.1c02391
摘要
Immune checkpoint blockade (ICB) therapy has been considered as an effective way to boost immune cells to recognize and attack tumors. However, side effects known as immune-related adverse events (irAEs) should be carefully managed. Here, we engineer immunosuppressive nanoparticles by coating PD-L1 overexpressed mesenchymal stem cells (MSCs) plasma membrane on poly lactic-co-glycolic acid nanoparticles (MSC-PD-L1+ NPs) for managing and reducing irAEs induced by immune checkpoint inhibitors. The nanoparticles can enrich at liver site after intravenous administration. In the high dose of anti-PD-L1 mAb-induced irAEs clinically relevant mouse model, a low dose of MSC-PD-L1+ NPs (2 mg/kg) sufficiently rescues hepatitis by inactivating T cells and macrophages in the liver tissue. More intriguingly, due to the dose threshold for nanoparticles to the tumor site, we unexpectedly find that the injected NPs do not affect the efficiency of ICB therapy to inhibit solid tumor growth. Such a strategy shows potential for managing the various cancer immunotherapy associated irAEs in clinical applications.
科研通智能强力驱动
Strongly Powered by AbleSci AI