Role of NKT cells and alpha-galactosyl ceramide.
Alfa-Galactosyl Ceramide was isolated from Ocean sponge which has antitumor effect against several tumors in in vivo animal model with no cytotoxicity. KRN7000(KRN) is the most potent alpha-Galactosyl Ceramide modified from the one isolated from Ocean sponge. KRN is also active against metastatic tumors through the activation ofanimal immune system. Research efforts in learning the mechanism of action, we found the important role of dendritic cells(DC) and NKT cells. NKT cells was first characterized in 1988 which is overlap some part with NK cells and T-Cells and majority is different from NK and T. KRN is active through the activation of DC and NKT in giving antigen specific immune stimulation in animal. This antigen specific stimulation is memorized by immune system and can reject second tumor challenge. KRN is not active in nude mice and NKT deficient animal. NKT cells level in blood is lower in patients with autoimmune disease, cancer, HIV positive or aplastic anemia. NKT rapidly releases IL-4 and IFN-gamma at high level when activated. NKT is CD1d and TCR restricted. NKT plays important role in autoimmune disease such as Type 1 Diabetes, Scleroderma and Systemic Lupus Erythematosus, infections such as Mycobacteria, Listeria and Malaria, GVHD control and tumor rejection. NKT acts as double edge sword, aggressive and suppressive ways. KRN can prevent the onset of Type 1 Diabetes, inhibit replication of hepatitis virus B in liver and suppress malaria replication in activating NKT cells. KRN can activate NKT through DC and activated NKT activates NK, T and macrophage. KRN also expands NKT cells and expanded NKT has full function. Although the exact role of DC and NKT is not clear, KRN clinical study results in conjunction with DC and NKT cell activation are expected.
Shimosaka
Akihiro
A
Pharmaceutical Division, Kirin Brewery Co, Ltd, Japan.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D005699:Galactosylceramides / Q000494:pharmacology* / Q000627:therapeutic use; D019337:Hematologic Neoplasms / Q000628:therapy; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000970:Antineoplastic Agents; D005699:Galactosylceramides; C103873:KRN 7000