Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment,yet their mechanism of action and individual components contributing to such actions remain to be delineated.Here,we show that a...Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment,yet their mechanism of action and individual components contributing to such actions remain to be delineated.Here,we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+T cell responses and mediating anti-tumor immunity.Mechanistically,both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells.Stimulation of interferon-βexpression is exclusively dependent on STING,and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene.Thus,the mRNA vaccine elicits STING-dependent antitumor immunity.展开更多
基金partially supported with a sponsored research grant from Stemirna Therapeutics,Chinafrom internal funding sources in Houston Methodist Research Institute,USA
文摘Lipid-formulated RNA vaccines have been widely used for disease prevention and treatment,yet their mechanism of action and individual components contributing to such actions remain to be delineated.Here,we show that a therapeutic cancer vaccine composed of a protamine/mRNA core and a lipid shell is highly potent in promoting cytotoxic CD8+T cell responses and mediating anti-tumor immunity.Mechanistically,both the mRNA core and lipid shell are needed to fully stimulate the expression of type I interferons and inflammatory cytokines in dendritic cells.Stimulation of interferon-βexpression is exclusively dependent on STING,and antitumor activity from the mRNA vaccine is significantly compromised in mice with a defective Sting gene.Thus,the mRNA vaccine elicits STING-dependent antitumor immunity.
