A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma  

作　　者：Mengran Guo Xing Duan Xingchen Peng Zhaohui Jin Hai Huang Wen Xiao Qian Zheng Yongqi Deng Na Fan Kepan Chen Xiangrong Song 

机构地区：[1]Department of Critical Care Medicine,Department of Clinical Pharmacy,Frontiers Science Center for Disease-related Molecular Network,State Key Laboratory of Biotherapy and Cancer Center,West China Hospital,Sichuan University,Chengdu 610000,China [2]West China School of Pharmacy,Sichuan University,Chengdu 610000,China

出　　处：《Nano Research》2023年第4期5357-5367,共11页纳米研究（英文版）

基　　金：supported by the National Key Research and Development Program of China(No.2021YFE0206600);Sichuan Province Science and Technology Support Program(Nos.2021YFSY0008 and 2020YFH0065);the Translational medicine fund of West China Hospital(No.CGZH19002);1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD18020/ZYJC18006).

摘　　要：Nasopharyngeal carcinoma(NPC)is a serious and highly invasive epithelial malignancy that is closely associated with Epstein‒Barr virus(EBV).Due to the lack of therapeutic vaccines for NPC,we selected EBV latent membrane protein 2(LMP2)as a preferable targeting antigen to develop a lipid-based LMP2-mRNA(mLMP2)vaccine.Full-length mLMP2 expressing LMP2 was first synthesized using an in vitro transcription method and then encapsulated into(2,3-dioleacyl propyl)trimethylammonium chloride(DOTAP)-based cationic liposomes to obtain the mRNA vaccine(LPX-mLMP2).The cell assays showed that the antigenpresenting cells were capable of highly efficient uptake of LPX-mLMP2 and expression of LMP2.LMP2 could subsequently be presented to form the peptide-major histocompatibility complex(pMHC).Furthermore,LPX-mLMP2 could accumulate in the spleen,express antigens,promote the maturation of dendritic cells and stimulate antigen-specific T-cell responses in vivo.It dramatically inhibited the tumor growth of the LMP2-expressing tumor model after three doses of vaccination.Additionally,the proliferation of antigen-specific T cells in the tumor site made a good sign for the promise of mRNA vaccines in virus-induced cancer.Overall,we provided a newly developed antigen-encoding mRNA vaccine with advantages against NPC.We also demonstrated that mRNA vaccines are attractive candidates for cancer immunotherapy.

关 键 词：mRNA vaccine latent membrane protein 2(LMP2) nasopharyngeal carcinoma Epstein-Barr virus(EBV) tumorinfiltrating lymphocytes 

分 类 号：R739.63[医药卫生—肿瘤]