A lipid-based LMP2-mRNA vaccine to treat nasopharyngeal carcinoma
Mengran Guo, Xing Duan, Xingchen Peng, Zhaohui Jin, Hai Huang, Wen Xiao, Qian Zheng, Yongqi Deng, Na Fan, Kepan Chen, Xiangrong Song
Abstract
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 antigen-presenting 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.