Generated SecPen_NY-ESO-1_ubiquitin-pulsed dendritic cell cancer vaccine elicits stronger and specific T cell immune responses

作     者：Yunkai Yang Xiaohan Guo Bo Hu Peng He Xiaowu Jiang Zuohuan Wang Huaxing Zhu Lina Hu Minghua Yu Meiqing Feng Yunkai Yang;Xiaohan Guo;Bo Hu;Peng He;Xiaowu Jiang;Zuohuan Wang;Huaxing Zhu;Lina Hu;Minghua Yu;Meiqing Feng

作者机构：Shanghai Engineering Research Center of ImmunoTherapeuticsSchool of PharmacyFudan UniversityShanghai 201203China Shanghai Novoprotein Biotechnology Co.Ltd.Shanghai 201203China Medical School of Yichun UniversityYichun 336000China Clinical Research Center2nd Affiliated HospitalMedical College of Zhejiang UniversityHangzhou 310009China Department of OncologyShanghai Pudong HospitalFudan University Pudong Medicine CenterShanghai 201399China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2021年第11卷第2期

页      面：476-487页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学] 

基　　金：funded by PDH-SPFDU Joint Research Fund(RHJJ2018-04,China) Shanghai Science and Technology Committee(No.19431903000,China) 

主　　题：Dendritic cells Cancer vaccine NY-ESO-1 SecPen Ubiquitin 

摘      要：Dendritic cell-based cancer vaccines(DC vaccines)have been proved efficient and safe in immunotherapy of various cancers,including melanoma,ovarian and prostate cancer.However,the clinical responses were not always satisfied.Here we proposed a novel strategy to prepare DC vaccines.In the present study,a fusion protein SNU containing a secretin-penetratin(SecPen)peptide,NY-ESO-1 and ubiquitin was designed and expressed.To establish the DC vaccine(DC-SNU),the mouse bone marrowderived DCs(BMDCs)were isolated,pulsed with SNU and maturated with cytokine cocktail.Then peripheral blood mononuclear cells(PBMCs)from C57 BL/6 mice inoculated intraperitoneally with DCSNU were separated and cocultured with MC38/MC38NY-ESO-1 tumor cells or DC vaccines.The results show that SNU was successfully expressed.This strategy made NY-ESO-1 entering cytoplasm of BMDCs more efficiently and degraded mainly by proteasome.As we expected,mature BMDCs expressed higher CD40,CD80 and CD86 than immature BMDCs.Thus,the PBMCs released more IFN-γand TNF-αwhen stimulated with DC-SNU in vitro again.What’s more,the PBMCs induced stronger and specific cytotoxicity towards MC38NY-ESO-1 tumor cells.Given the above,it demonstrated that DC-SNU loaded with SecPen and ubiquitin-fused NY-ESO-1 could elicit stronger and specific T cell immune responses.This strategy can be used as a platform for DC vaccine preparation and applied to various cancers treatment.