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 membra...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.展开更多
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)+1 种基金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).
文摘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.
