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免疫刺激型CpG寡核苷酸的最新进展。

Recent advances in immunostimulatory CpG oligonucleotides.

作者信息

Rothenfusser Simon, Tuma Evelyn, Wagner Moritz, Endres Stefan, Hartmann Gunther

机构信息

Department of Internal Medicine, Division of Clinical Pharmacology, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.

出版信息

Curr Opin Mol Ther. 2003 Apr;5(2):98-106.

PMID:12772497
Abstract

The vertebrate immune system has evolved a mechanism to detect CpG motifs within microbial DNA (CpG DNA). Synthetic oligonucleotides containing CpG motifs (CpG ODNs) are potent immunomodulatory molecules and outstanding vaccine adjuvants. A number of recent findings have greatly improved our understanding of the biology of CpG DNA, and the immunological effects of CpG DNA are now recognized to be distinct in mouse and human. The plasmacytoid dendritic cell (PDC) was identified to play a pivotal role in mediating CpG-induced immune responses. So far, the B-cell is the only other immune cell subset in humans besides the PDC, equipped with the toll-like receptor-9 to detect CpG motifs. The information on these two prime CpG-sensitive cells has allowed the identification of novel CpG ODNs with distinct functional activity. Together with exciting contributions from animal studies, the way seems to be paved for the successful clinical development of this novel class of molecular therapeutics.

摘要

脊椎动物免疫系统已进化出一种机制来检测微生物DNA(CpG DNA)中的CpG基序。含有CpG基序的合成寡核苷酸(CpG ODN)是强效的免疫调节分子和出色的疫苗佐剂。最近的一些发现极大地增进了我们对CpG DNA生物学特性的理解,并且现在人们认识到CpG DNA的免疫效应在小鼠和人类中是不同的。浆细胞样树突状细胞(pDC)被确定在介导CpG诱导的免疫反应中起关键作用。到目前为止,B细胞是人类中除pDC之外唯一配备有Toll样受体9以检测CpG基序的其他免疫细胞亚群。关于这两种主要的CpG敏感细胞的信息使得能够鉴定出具有不同功能活性的新型CpG ODN。连同动物研究的令人兴奋的贡献,似乎为这类新型分子疗法的成功临床开发铺平了道路。

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