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

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.