Tashiro Takuya
Glycosphingolipid Synthesis Group, Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Saitama, Japan.
Biosci Biotechnol Biochem. 2012;76(6):1055-67. doi: 10.1271/bbb.120072. Epub 2012 Jun 7.
KRN7000, an anticancer drug candidate developed by Kirin Brewery Co. in 1995, is an α-galactosyl ceramide. It is a ligand making a complex with CD1d protein, and it stimulates invariant natural killer T (NKT) cells, which are one of the lineages of immunocytes. NKT cells activated by recognition of the CD1d/KRN7000 complex with its invariant T-cell receptor (TCR) can induce both protective and regulatory immune responses. To determine the recognition and activation mechanisms of NKT cells and to develop drug candidates more effective than KRN7000, a large number of analogs of KRN7000 have been synthesized. Some of them show potent bioactivities and have the potential of being utilized as therapeutic agents. In this review, structure-activity relationship studies of novel glycolipids which stimulate NKT cells efficiently are summarized.
KRN7000是麒麟啤酒公司于1995年研发的一种抗癌候选药物，它是一种α-半乳糖基神经酰胺。它是一种能与CD1d蛋白形成复合物的配体，可刺激免疫细胞谱系之一的不变自然杀伤T（NKT）细胞。通过其不变T细胞受体（TCR）识别CD1d/KRN7000复合物而被激活的NKT细胞可诱导保护性和调节性免疫反应。为了确定NKT细胞的识别和激活机制，并开发比KRN7000更有效的候选药物，人们合成了大量KRN7000的类似物。其中一些表现出强大的生物活性，具有用作治疗剂的潜力。在这篇综述中，总结了有效刺激NKT细胞的新型糖脂的构效关系研究。
