鱼精蛋白
阳离子脂质体
免疫系统
生物
抗原
佐剂
癌症疫苗
信使核糖核酸
免疫
免疫学
遗传增强
免疫疗法
生物化学
基因
肝素
作者
Yaping Mai,Jueshuo Guo,Yue Zhao,Shijie Ma,Yanhui Hou,Jianhong Yang
标识
DOI:10.1016/j.cellimm.2020.104143
摘要
Immunization with synthetic mRNA encoding tumor-associated antigens is an emerging vaccine strategy for the treatment of cancer. In order to prevent mRNA degradation, promote antigen-presenting cells antigen presentation, and induce an anti-tumor immune response, we investigated the nasal administration of mRNA vaccines with positively charged protamine to concentrate mRNA, form a stable polycation-mRNA complex, and encapsulate the complex with DOTAP/Chol/DSPE-PEG cationic liposomes. Cationic liposome/protamine complex (LPC) showed significantly greater efficiency in uptake of vaccine particles in vitro and stronger capacities to stimulate dendritic cell maturation, which further induced a potent anti-tumor immune response. Intranasal immunization of mice with cationic LPC containing mRNA encoding cytokeratin 19 provoked a strong cellular immune response and slowed tumor growth in an aggressive Lewis lung cancer model. The results of this study provide evidence that cationic LPC can be used as a safe and effective adjuvant and this mRNA formulation provides a basis for anti-cancer vaccination of humans.
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