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Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy

查看全文 作　　者：Xiaoxue [1]Xie;Yi [1]Feng;Hanxi [1]Zhang;Qingqing [1]Su;Ting [1]Song;Geng [1]Yang;Ningxi [1]Li;Xiaodan [1]Wei;Tingting [1]Li;Xiang [1]Qin;Shun [1]Li;Chunhui [1]Wu;Xiaojuan [3]Zhang;Guixue [3]Wang;Yiyao [1,2]Liu;Hong [1]Yang 高影响力作者 机构地区：[1]Department of Biophysics,School of Life Science and Technology,University of Electronic Science and Technology of China,Chengdu,610054,Sichuan,PR China;[2]TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Hospital of Chengdu University of Traditional Chinese Medicine,No.39 Shi-er-qiao Road,Chengdu,610072,Sichuan,PR China;[3]Key Laboratory of Biorheological Science and Technology,Ministry of Education,State and Local Joint Engineering Laboratory for Vascular Implants,Bioengineering College of Chongqing University,Chongqing,400030,PR China高影响力机构 出　　处：《Bioactive Materials》索引2022年第7卷第10期,共13页高影响力期刊 基　　金：by the National Natural Science Foundation of China(U19A2006,12132004,12032007,11972111,31900940,32071304,32171309,32171395);the Sichuan Science and Technology Program(21YJ0130);the Joint Funds of Center for Engineering Medicine(ZYGX2021YGLH010,ZYGX2021YGLH017,ZYGX2021YGLH023);the technical support from the Public Experiment Centre of State Bioindustrial Base(Chongqing). 摘　　要：The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment(TME).Here,we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes(TILs)using hybrid micelles(HM),which encapsulated colony stimulating factor 1 receptor(CSF1-R)inhibitor BLZ-945 and indoleamine 2,3-dioxygenase(IDO)inhibitor NLG-919 in its core and displayed a model antigen ovalbumin(OVA)on its surface(denoted as BN@HM-OVA).The bioactive nanovaccine is coated with a polyethylene glycol(PEG)shell for extending nanoparticle circulation.The shell can be shed in response to the weakly acidic tumor microenvironment.The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs.We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells(DCs)and drugs transportation into M1-like tumor-associated macrophages(TAMs)and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME.Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment,leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models.Furthermore,combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition,based on the optimal timing and sequence of PD-1 blockade against T cell receptor.This research provides a new strategy for the development of efficient cancer immunotherapy. 关 键 词：Bioactive nanovaccine Cancer immunotherapy IDO inhibitor TAMS TME
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