免疫检查点
肿瘤微环境
免疫疗法
癌症研究
免疫系统
封锁
基因沉默
遗传增强
黑色素瘤
医学
免疫学
生物
作者
Yong Feng,Jiayan Wu,Jie Chen,Lin Lin,Sijia Zhang,Zhiyu Yang,Pingjie Sun,Yanhui Li,Huayu Tian,Xuesi Chen
出处
期刊:Nano Today
[Elsevier]
日期:2021-06-01
卷期号:38: 101194-101194
被引量:25
标识
DOI:10.1016/j.nantod.2021.101194
摘要
Despite the unparalleled tumor growth inhibition and significantly prolonged survival achieved by immune checkpoint blockade (ICB) therapy, more and more adaptive resistance to ICB therapy in clinical practice put patients at risk of uncontrollable tumor growth and tumor relapse. Hence, in this work, we constructed a targeting dual gene delivery system loading pshVEGF-A and pshPD-L1 against murine melanoma to overcome adaptive resistance for efficacious anti-tumor immunotherapy. We reported immune checkpoint blockade by PD-L1 gene silencing induced adaptive resistance through the VEGF-A/VEGF-R2 signal pathway. Therefore, the combination of PD-L1 and VEGF-A gene silencing eliminated adaptive resistance to ICB therapy. Besides, pshVEGF-A as an antiangiogenic agent achieved tumor vessel normalization and reprogramed tumor immune microenvironment towards an immune-supportive profile, synergizing with pshPD-L1 for significant tumor inhibition. This revolutionary dual gene therapy strategy contributed to the diversity of immune combination therapy and had a potential for clinical application in the near future.
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