Engineering Polymeric Prodrug Nanoplatform for Vaccination Immunotherapy of Cancer

doi:10.1021/acs.nanolett.0c01140

	Engineering Polymeric Prodrug Nanoplatform for Vaccination Immunotherapy of Cancer
	Zhou, Lei 3,4,5; Hou, Bo 4,5; Wang, Dangge 4,5; Sun, Fang 4,5; Song, Rundi 4,5; Shao, Qian 1; Wang, Hao 3; Yu, Haijun 2,4,5; Li, Yaping 2,4,5
刊名	NANO LETTERS
	2020-06-10
卷号	20 期号:6 页码:4393-4402
关键词	Polymeric prodrug Neoantigen Adaptive immune response Personalized immunotherapy Nanoparticles
ISSN号	1530-6984
DOI	10.1021/acs.nanolett.0c01140
通讯作者	Yu, Haijun(hjyu@simm.ac.cn) ; Li, Yaping(ypli@simm.ac.cn)
英文摘要	Neoantigen-based cancer vaccines are promising for boosting cytotoxic T lymphocyte (CTL) responses. However, the therapeutic effect of cancer vaccines is severely blunted by functional suppression of the dendritic cells (DCs). Herein, we demonstrated an acid-responsive polymeric nanovaccine for activating the stimulator of interferon genes (STING) pathway and improving cancer immunotherapy. The nanovaccines were fabricated by integrating an acid-activatable polymeric conjugate of the STING agonist and neoantigen into one single nanoplatform. The nanovaccines efficiently accumulated at the lymph nodes for promoting DC uptake and facilitating cytosol release of the neoantigens. Meanwhile, the STING agonist activated the STING pathway in the DCs to elicit interferon-beta secretion and to boost T-cell priming with the neoantigen. The nanovaccine dramatically inhibited tumor growth and occurrence of B16-OVA melanoma and 4T1 breast tumors in immunocompetent mouse models. Combination immunotherapy with the nanovaccines and anti-PD-L1 antibody demonstrated further improved antitumor efficacy in a 4T1 breast tumor model.
资助项目	National Natural Science Foundation of China[51873228] ; National Natural Science Foundation of China[31671024] ; National Natural Science Foundation of China[81521005] ; Natural Science Foundation of Shandong Province[ZR2019LZL020] ; State Key Laboratory of Drug Research[SIMM2004KF-04]
WOS关键词	INNATE IMMUNE RECOGNITION ; DENDRITIC CELLS ; POTENT ; DELIVERY ; MICROENVIRONMENT ; NANOPARTICLES ; MICELLEPLEXES ; INTERFERONS ; NANOVACCINE ; ACTIVATION
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000541691200043
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/291801]
专题	中国科学院上海药物研究所
通讯作者	Yu, Haijun; Li, Yaping
作者单位	1.Shandong Inst Canc Prevent & Treatment, Jinan 250117, Shandong, Peoples R China 2.Yantai Inst Mat Med, Yantai Key Lab Nanomedicole & Adv Preparat, Yantai 264000, Shandong, Peoples R China 3.China State Inst Pharmaceut Ind, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Zhou, Lei,Hou, Bo,Wang, Dangge,et al. Engineering Polymeric Prodrug Nanoplatform for Vaccination Immunotherapy of Cancer[J]. NANO LETTERS,2020,20(6):4393-4402.
APA	Zhou, Lei.,Hou, Bo.,Wang, Dangge.,Sun, Fang.,Song, Rundi.,...&Li, Yaping.(2020).Engineering Polymeric Prodrug Nanoplatform for Vaccination Immunotherapy of Cancer.NANO LETTERS,20(6),4393-4402.
MLA	Zhou, Lei,et al."Engineering Polymeric Prodrug Nanoplatform for Vaccination Immunotherapy of Cancer".NANO LETTERS 20.6(2020):4393-4402.