TLR9型
CpG寡核苷酸
先天免疫系统
免疫系统
CpG站点
背景(考古学)
抗原
TLR7型
生物
免疫学
获得性免疫系统
细胞生物学
化学
Toll样受体
生物化学
DNA甲基化
古生物学
基因表达
基因
作者
Zifu Zhong,Yong Chen,Kim Deswarte,Henri Lauwers,Emily De Lombaerde,Xiaole Cui,Simon Van Herck,Tingting Ye,Mark Gontsarik,Stefan Lienenklaus,Niek N. Sanders,Bart N. Lambrecht,Stefaan De Koker,Bruno G. De Geest
标识
DOI:10.1002/adhm.202301687
摘要
Pharmacological strategies to activate innate immune cells are of great relevance in the context of vaccine design and anticancer immune therapy, to mount broad immune responses able to clear infection and malignant cells. Synthetic CpG oligodeoxynucleotides (CpG-ODNs) are short single-stranded DNA molecules containing unmethylated CpG dinucleotides and a phosphorothioate backbone. Class B CpG ODNs activate robust innate immune responses through a TLR9-dependent NF-κB signaling pathway. This feature is attractive to exploit in the context of vaccine design and cancer immunotherapy. Soluble CpG-ODNs cause hepatic toxicity, which reduces its therapeutic applicability. The formulation of class B CpG ODN1826 in lipid nanoparticles (LNPs) containing an ionizable cationic lipid that complexes CpG through electrostatic interaction is reported. Upon local administration, LNP-formulated CpG drains to lymph nodes and triggers robust innate immune activation. Unformulated, soluble, CpG, by contrast, is unable to induce robust innate activation in draining lymph nodes and is distributed systemically. In a vaccination setting, LNP-formulated CpG, admixed with a protein antigen, induces higher antigen-specific antibody titers and T cell responses than antigen admixed with unformulated soluble CpG.
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