信使核糖核酸
佐剂
癌症免疫疗法
Toll样受体
抗原呈递
脂质A
TLR2型
免疫系统
TLR4型
树突状细胞
抗原
生物
癌症研究
免疫疗法
免疫学
T细胞
基因
脂多糖
先天免疫系统
生物化学
作者
Hongxia Zhang,Xinru You,Xiaojuan Wang,Lei Cui,Zining Wang,Feifei Xu,Mengyun Li,Yang Zhou,Jinyun Liu,Peng Huang,Yang Kang,Jun Wu,Xiaojun Xia
标识
DOI:10.1073/pnas.2005191118
摘要
Intracellular delivery of messenger RNA (mRNA)-based cancer vaccine has shown great potential to elicit antitumor immunity. To achieve robust antitumor efficacy, mRNA encoding tumor antigens needs to be efficiently delivered and translated in dendritic cells with concurrent innate immune stimulation to promote antigen presentation. Here, by screening a group of cationic lipid-like materials, we developed a minimalist nanovaccine with C1 lipid nanoparticle (LNP) that could efficiently deliver mRNA in antigen presenting cells with simultaneous Toll-like receptor 4 (TLR4) activation and induced robust T cell activation. The C1 nanovaccine entered cells via phagocytosis and showed efficient mRNA-encoded antigen expression and presentation. Furthermore, the C1 lipid nanoparticle itself induced the expression of inflammatory cytokines such as IL-12 via stimulating TLR4 signal pathway in dendritic cells. Importantly, the C1 mRNA nanovaccine exhibited significant antitumor efficacy in both tumor prevention and therapeutic vaccine settings. Overall, our work presents a C1 LNP-based mRNA cancer nanovaccine with efficient antigen expression as well as self-adjuvant property, which may provide a platform for developing cancer immunotherapy for a wide range of tumor types.
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