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T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy

文献类型：期刊论文

作者Zhai, Yihui2,3,4; Wang, Jinming1,5; Lang, Tianqun2,3,4; Kong, Ying6; Rong, Rong6; Cai, Ying2,3,4; Ran, Wei2,3,4; Xiong, Fengqin2,3,7; Zheng, Chao2,3,7; Wang, Yanke8
刊名NATURE NANOTECHNOLOGY
出版日期2021-11
卷号16期号:11页码:1271-+
ISSN号1748-3387
DOI10.1038/s41565-021-00972-7
文献子类Article
英文摘要Impaired type I interferons (IFNs) may cause immune deficiency in tumours. Current supplementary IFN therapy partially restores anticancer immunity but simultaneously induces immune evasion by upregulating multiple immune checkpoints. Here we create a T lymphocyte membrane-decorated epigenetic nanoinducer that is engineered with programmed cell death protein 1 (PD1), which we call OPEN, for the delivery of the IFN inducer ORY-1001. OPEN increases IFNs and blocks IFN-induced immune checkpoint upregulation. OPEN also targets tumours that express programmed cell death ligand 1 (PDL1) through PDL1/PD1 recognition and subsequently triggers the internalization of OPEN and immune checkpoint proteins. OPEN, which is loaded with ORY-1001, upregulates intratumoural IFNs and downstream major histocompatibility complex I and PDL1. The replenished PDL1 enables further ligation of OPEN, which in turn blocks PDL1. These sequential processes result in an eight- and 29-fold increase of the intratumoural densities of total and active cytotoxic T lymphocytes, respectively, and a strong inhibition of xenograft tumour growth. This T lymphocyte membrane-decorated epigenetic nanoinducer presents a generalizable platform to boost antitumour immunity. Type I interferons (IFNs) have strong antitumour activity yet their clinical use is limited by their off-target toxicity and by their effect on immune evasion. Here the authors design a biomimetic nanoparticle loaded with an IFN inducer, which can at the same time replenish intratumoural IFNs and reduce their immunosuppressive activity, showing therapeutic efficacy in several animal tumour models.
WOS关键词BREAST-CANCER ; CHECKPOINT BLOCKADE ; ANTITUMOR IMMUNITY ; I INTERFERON ; CELLS ; ERADICATION ; METASTASIS ; INHIBITOR ; DELIVERY
WOS研究方向Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:000700975900001
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/309365]  
专题新药研究国家重点实验室
通讯作者Zhang, Pengcheng; Li, Yaping
作者单位1.Shanghai Jiao Tong Univ, Sch Biomed Engn, Shanghai, Peoples R China;
2.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China;
3.Chinese Acad Sci, Ctr Pharmaceut, Shanghai Inst Mat Med, Shanghai, Peoples R China;
4.Univ Chinese Acad Sci, Beijing, Peoples R China;
5.Shanghai Jiao Tong Univ, Ren Ji Hosp, Sch Med, Renji Med X Stem Cell Res Ctr,Dept Urol,State Key, Shanghai, Peoples R China;
6.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai, Shandong, Peoples R China;
7.China State Inst Pharmaceut Ind, Shanghai, Peoples R China;
8.Zhangjiang Lab, Natl Facil Prot Sci Shanghai, Shanghai, Peoples R China;
9.Bohai Rim Adv Res Inst Drug Discovery, Yantai, Shandong, Peoples R China
推荐引用方式
GB/T 7714		 Zhai, Yihui,Wang, Jinming,Lang, Tianqun,et al. T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy[J]. NATURE NANOTECHNOLOGY,2021,16(11):1271-+.
APA Zhai, Yihui.,Wang, Jinming.,Lang, Tianqun.,Kong, Ying.,Rong, Rong.,...&Li, Yaping.(2021).T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy.NATURE NANOTECHNOLOGY,16(11),1271-+.
MLA Zhai, Yihui,et al."T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy".NATURE NANOTECHNOLOGY 16.11(2021):1271-+.

入库方式： OAI收割

来源：上海药物研究所

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