Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy

doi:10.1038/s41401-020-00570-8

	Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy
	He, Zhi-di 1,2; Zhang, Meng 1; Wang, Yong-hui 1,2; He, Yang 1,2; Wang, Hai-rui 1,3; Chen, Bin-fan 1,2; Tu, Bin 1,2; Zhu, Si-qi 1,4; Huang, Yong-zhuo 1,2,5,6
刊名	ACTA PHARMACOLOGICA SINICA
	2020-12-11
页码	8
关键词	tumor-targeted delivery immunogenic cell death PD-1 PD-L1 blockade tumor immune microenvironment irinotecan JQ1 immune checkpoint
ISSN号	1671-4083
DOI	10.1038/s41401-020-00570-8
通讯作者	Huang, Yong-zhuo(yzhuang@simm.ac.cn)
英文摘要	Immune checkpoint blockade therapy has become a first-line treatment in various cancers. But there are only a small percent of colorectal patients responding to PD-1/PD-L1 blockage immunotherapy. How to increase their treatment efficacy is an urgent and clinically unmet need. It is acknowledged that immunogenic cell death (ICD) induced by some specific chemotherapy can enhance antitumor immunity. Chemo-based combination therapy can yield improved outcomes by activating the immune system to eliminate the tumor, compared with monotherapy. Here, we develop a PD-L1-targeting immune liposome (P-Lipo) for co-delivering irinotecan (IRI) and JQ1, and this system can successfully elicit antitumor immunity in colorectal cancer through inducing ICD by IRI and interfering in the immunosuppressive PD-1/PD-L1 pathway by JQ1. P-Lipo increases intratumoral drug accumulation and promotes DC maturation, and thereby facilitates adaptive immune responses against tumor growth. The remodeling tumor immune microenvironment was reflected by the increased amount of CD8(+) T cells and the release of IFN-gamma, and the reduced CD4(+)Foxp3(+) regulatory T cells (Tregs). Collectively, the P-Lipo codelivery system provides a chemo-immunotherapy strategy that can effectively remodel the tumor immune microenvironment and activate the host immune system and arrest tumor growth.
资助项目	NFSC[81925035] ; NFSC[81673382] ; NFSC[81521005] ; Strategic Priority Research Program of CAS[XDA12050307] ; National Special Project for Significant New Drugs Development[2018ZX09711002-010-002] ; Shanghai SciTech Innovation Initiative[19431903100] ; Shanghai SciTech Innovation Initiative[18430740800] ; Shanghai Collaborative Innovation Group of Early Diagnosis and Precise Treatment of Hemangiomas and Vascular Malformations[SSMU-ZDCX20180701]
WOS关键词	METASTATIC COLORECTAL-CANCER ; INTERFERON-GAMMA ; CELL-DEATH ; INHIBITORS ; IMMUNITY ; GROWTH
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000597776500002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/296226]
专题	中国科学院上海药物研究所
通讯作者	Huang, Yong-zhuo
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 3.Guangzhou Univ Chinese Med, Artemisinin Res Ctr, Guangzhou 510450, Peoples R China 4.Zhejiang Univ City Coll, Dept Pharmacol, Hangzhou 310015, Peoples R China 5.NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Shanghai 201203, Peoples R China 6.Chinese Acad Sci, Inst Drug Res & Dev, Zhongshan Branch, Zhongshan 528451, Peoples R China
推荐引用方式 GB/T 7714	He, Zhi-di,Zhang, Meng,Wang, Yong-hui,et al. Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy[J]. ACTA PHARMACOLOGICA SINICA,2020:8.
APA	He, Zhi-di.,Zhang, Meng.,Wang, Yong-hui.,He, Yang.,Wang, Hai-rui.,...&Huang, Yong-zhuo.(2020).Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy.ACTA PHARMACOLOGICA SINICA,8.
MLA	He, Zhi-di,et al."Anti-PD-L1 mediating tumor-targeted codelivery of liposomal irinotecan/JQ1 for chemo-immunotherapy".ACTA PHARMACOLOGICA SINICA (2020):8.