Toll-like receptor 3 agonist complexed with cationic liposome augments vaccine-elicited antitumor immunity by enhancing TLR3-IRF3 signaling and type I interferons in dendritic cells

	Toll-like receptor 3 agonist complexed with cationic liposome augments vaccine-elicited antitumor immunity by enhancing TLR3-IRF3 signaling and type I interferons in dendritic cells
	Ce Wang; Yan Zhuang; Yijuan Zhang; Zichao Luo; Ningning Gao; Ping Li; Hong Pan; Lintao Cai; Yifan Ma
刊名	Vaccine
	2012
英文摘要	Cancer vaccine-based immunotherapy is emerging as a novel therapeutic strategy for cancer treatment. However, its antitumor effect remains unsatisfied due to the poor immunogenicity of tumor antigens (Ags). Although polyriboinosinic: polyribocytidylic acid (PIC), a TLR3 agonist, has been reported as a promising adjuvant for cancer vaccines, its immunopotency may be limited by insufficient cellular penetration. In the present study, we incorporated PLC into DOTAP cationic liposome to generate PIC-DOTAP Liposome Complex (PDLC) nanoparticles. The results showed that PDLC was more potent than DOTAP or PIC to enhance vaccine-induced tumor-specific cytotoxic T lymphocyte (CTL) response and IFN-gamma production. Moreover, two doses of PDLC vaccines remarkably suppressed tumor growth in mice, which involved the participance of CD8(+) T cells and depended on the presence of Ag. The superior antitumor effect of PDLC vaccines could be attributable to enhanced maturation of mouse bone-marrow dendritic cells (BMDCs) and increased production of type I IFNs. More importantly. PDLC strengthened the TLR3 signaling in BMDCs by enhancing the interaction of PLC with TLR3 and augmenting downstream IRF-3 phosphorylation, as well as elevating IRF-3/IRF-7 mRNA transcription. Taking together, the complex of PLC and DOTAP liposomes enhanced PIC uptake and consequential TLR3 signaling in BMDCs, which in turn promoted DC maturation and type I IFN production, thereby augmenting the antitumor effect of cancer vaccines.
收录类别	SCI
原文出处	http://ac.els-cdn.com/S0264410X12007311/1-s2.0-S0264410X12007311-main.pdf?_tid=445bd100-079b-11e5-8bf8-00000aab0f01&acdnat=1433080095_8dd8f9f3b95a972970f6ba93580b0160
语种	英语
内容类型	期刊论文
源URL	[http://ir.siat.ac.cn:8080/handle/172644/3933]
专题	深圳先进技术研究院_医工所
作者单位	Vaccine
推荐引用方式 GB/T 7714	Ce Wang,Yan Zhuang,Yijuan Zhang,et al. Toll-like receptor 3 agonist complexed with cationic liposome augments vaccine-elicited antitumor immunity by enhancing TLR3-IRF3 signaling and type I interferons in dendritic cells[J]. Vaccine,2012.
APA	Ce Wang.,Yan Zhuang.,Yijuan Zhang.,Zichao Luo.,Ningning Gao.,...&Yifan Ma.(2012).Toll-like receptor 3 agonist complexed with cationic liposome augments vaccine-elicited antitumor immunity by enhancing TLR3-IRF3 signaling and type I interferons in dendritic cells.Vaccine.
MLA	Ce Wang,et al."Toll-like receptor 3 agonist complexed with cationic liposome augments vaccine-elicited antitumor immunity by enhancing TLR3-IRF3 signaling and type I interferons in dendritic cells".Vaccine (2012).