Structure-activity relationship studies of novel glycosphingolipids that stimulate natural killer T-cells.
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.
Glycosphingolipid Synthesis Group, Laboratory for Immune Regulation, Research Center for Allergy and Immunology, RIKEN, Saitama, Japan. tashiro@rcai.riken.jp
Takuya
T
Tashiro
D000818:Animals; D055610:Antigens, CD1d / Q000276:immunology / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005699:Galactosylceramides / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006028:Glycosphingolipids / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D055611:Natural Killer T-Cells / Q000187:drug effects* / Q000276:immunology; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D013329:Structure-Activity Relationship; D058408:Th1-Th2 Balance / Q000187:drug effects
D055610:Antigens, CD1d; D000970:Antineoplastic Agents; C526877:CD1D protein, human; D016207:Cytokines; D005699:Galactosylceramides; D006028:Glycosphingolipids; D011948:Receptors, Antigen, T-Cell; C103873:KRN 7000