Dow Steven
Department of Microbiology, Colorado State University, Ft. Collins, CO 80523, USA.
Expert Opin Drug Deliv. 2008 Jan;5(1):11-24. doi: 10.1517/17425247.5.1.11.
Cationic liposome-nucleic acid complexes, which were originally developed for use as non-viral gene delivery vectors, may now have an equally important application as immunotherapeutic drugs. Recent studies have highlighted the ability of cationic liposomes to potently activate the innate immune system when used to deliver certain Toll-like receptor (TLR) agonists. The immune-enhancing properties of cationic liposomes have been most clearly demonstrated when combined with nucleic acid agonists for endosomally located TLRs, including TLR3, TLR7/8 and TLR9. Immune potentiation by cationic liposomes likely results from the combined effects of endosomal targeting, protection of nucleic acids from extracellular degradation, and from signaling via newly identified cytoplasmic receptors for nucleic acids. The potent innate immune stimulatory properties of liposome-nucleic acid complexes make them particularly attractive as non-specific immunotherapeutics and as vaccine adjuvants. Liposome-nucleic acid complexes have demonstrated impressive anticancer activity in a number of different animal tumor models. Moreover, liposome-nucleic acid complexes have also been shown to be effective for immunotherapy of acute viral and bacterial infections, as well as chronic fungal infections. When used as vaccine adjuvants, liposome-nucleic acid complexes target antigens for efficient uptake by dendritic cells and are particularly effective in eliciting CD8(+) T-cell responses to protein antigens. Thus, liposome-nucleic acid complexes form a potent and versatile immunotherapeutic platform.
阳离子脂质体 - 核酸复合物最初被开发用作非病毒基因递送载体,现在可能作为免疫治疗药物具有同样重要的应用。最近的研究强调了阳离子脂质体在用于递送某些 Toll 样受体(TLR)激动剂时能够有效激活先天免疫系统的能力。当与用于内体定位的 TLR(包括 TLR3、TLR7/8 和 TLR9)的核酸激动剂联合使用时,阳离子脂质体的免疫增强特性得到了最清楚的证明。阳离子脂质体的免疫增强作用可能源于内体靶向、保护核酸免受细胞外降解以及通过新发现的核酸细胞质受体进行信号传导的综合作用。脂质体 - 核酸复合物强大的先天免疫刺激特性使其作为非特异性免疫治疗剂和疫苗佐剂特别具有吸引力。脂质体 - 核酸复合物在许多不同的动物肿瘤模型中已显示出令人印象深刻的抗癌活性。此外,脂质体 - 核酸复合物也已被证明对急性病毒和细菌感染以及慢性真菌感染的免疫治疗有效。当用作疫苗佐剂时,脂质体 - 核酸复合物靶向抗原以便被树突状细胞有效摄取,并且在引发针对蛋白质抗原的 CD8(+) T 细胞反应方面特别有效。因此,脂质体 - 核酸复合物形成了一个强大且通用的免疫治疗平台。