文献类型：期刊文献

英文题名：Spatiotemporally controllable diphtherin transgene system and neoantigen immunotherapy

作者：He, Muye[1,2];Sun, Yuji[2];Cheng, Yi[2];Wang, Jie[2];Zhang, Miao[2];Sun, Rui[2];Hou, Xinyu[2];Xu, Jiajun[2];He, Hai[2];Wang, Hongtao[2];Yuan, Zeting[2,3];Lan, Minbo[1];Zhao, Yuzheng[2,4,5];Yang, Yi[2,4,6];Chen, Xianjun[2,4,6,8];Gao, Feng[1,2,4,7]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China;[4]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[5]Chinese Acad Med Sci, Res Unit New Tech Live Cell Metab Imaging, Beijing, Peoples R China;[6]Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[7]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 130 Meilong Rd, Shanghai 200237, Peoples R China;[8]East China Univ Sci & Technol, Sch Pharm, Synthet Biol & Biotechnol Lab, State Key Lab Bioreactor Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2023

卷号：355

起止页码：538

外文期刊名：JOURNAL OF CONTROLLED RELEASE

收录：;EI(收录号：20230913644871);WOS:【SCI-EXPANDED(收录号:WOS:000942555000001)】；

基金：This work was sponsored by National Key Research and Development Program of China (contract No. 2019YFA0904800) , National Natural Science Foundation of China (32030065, 31722033, 92049304 to Y.Z.) , Shanghai Sailing Program (contract No. 21YF1410300) , Sci- ence and Technology Commission of Shanghai Municipality (contract No. 10DZ2220500) and The Shanghai Committee of Science and Tech- nology (grant No. 11DZ2260600) . Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism (Y.Z.) , Research Unit of New Techniques for Live -cell Metabolic Imaging (Chinese Academy of Medical Sciences, 2019-I2M-5-013 to Y.Z.) , the State Key Laboratory of Bioreactor Engineering, the Fundamental Research Funds for the Central Universities.

语种：英文

外文关键词：Light-switchable diphtherin gene expression; Melanoma; Immunotherapy; Neoantigen; Nanoparticle delivery system

摘要：Individualized immunotherapy has attracted great attention due to its high specificity, effectiveness, and safety. We used an exogenous antigen to label tumor cells with MHC I molecules, which allowed neoantigen-specific T cells to recognize and kill tumor cells. A neoantigen vaccine alone cannot achieve complete tumor clearance due to a tumor immunosuppressive microenvironment. The LightOn system was developed to effectively eliminate tumor cells through the spatiotemporally controllable expression of diphtheria toxin A fragment, leading to antigen release in the tumor region. These antigens stimulated and enhanced immunological function and thus, recruited neoantigen-specific T cells to infiltrate tumor tissue. Using the nanoparticle delivery system, neoantigens produced higher delivery efficiency to lymph nodes and improved tumor targeting ability for tumor cell labelling. Good tumor inhibition and prolonged survival were achieved, while eliciting a strong immune response. The combination of a spatiotemporally controllable transgene system with tumor neoantigen labeling has great potential for tumor immunotherapy.