Combination of a cationic complexes loaded with mRNA and α-Galactose ceramide enhances antitumor immunity and affects the tumor immune microenvironment.

mRNA vaccination is considered to be a promising strategy for tumor immunotherapy. Among, adequate antigen expression and regulation of tumor immune microenvironment are still the key to achieving therapeutic immounotherapy. In oreder to protect mRNA delivered to cells and reverse damaged dendritic cells(DCs), a novel vaccine delivery system composed of an α-Galactose ceramide/cationic liposome complex(α-GC-Lip) was constructed. The α-GC-liposome/protamine/mRNA vaccine complexes(α-GC-LPR) enabled the mRNA to be successfully translated into protein in the cytoplasm of antigen-presenting cells. Further, α-GC-LPR could stimulate dendritic cell maturation via significantly increasing the expression of bone marrow-derived cells(BMDCs) surface molecules and secretion of cytokines to improve the efficacy of immunotherapy. In vivo study, the α-GC-LPR was combined with programmed cell death protein 1(PD-1) inhibitor could activate natural killer cell(NK), T cells as well as significantly reduce the immunosuppression of immune cells, which induced strong antigen-specific immunity in breast cancer model. Our study indicated that the α-GC-LPR combined with immune checkpoint inhibitors as a potential design strategy to effectively enhance the antitumor immune response.