International Journal of Hematology

, Volume 76, Supplement 1, pp 277–279

Role of NKT cells and α-Galactosyl Ceramide

  • Akihiro Shimosaka
Immune and Cell Therapy for Hematological Disorders

Abstract

Alfa-Galactosyl Ceramide was isolated from Ocean sponge which has antitumor effect against several tumors inin vivo animal model with no cytotoxicity. KRN7000(KRN) is the most potent α-Galactosyl Ceramide modified from the one isolated from Ocean sponge. KRN is also active against metastatic tumors through the activation of animal 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-γ 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.

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References

  1. 1.
    Kobayashi E, Motoki K, Uchida T, Fukushima H, Koezuka Y. KRN7000, a novel immunomodulator, and its antitumor activity.Oncol Res. 1995;7:529–534.PubMedGoogle Scholar
  2. 2.
    Yamaguchi Y, Ueno H, Maeda K, et al. Enhancing effects of (2S,3S,4R)-1-O-(α-D-galacto-pyranosyl)-2-(N-hexacosanoylamin o)-1,3,4-octadecanetriol (KRN7000) on anigen-presenting function of antigen-presenting cells and antimetastatic activity of KRN7000-pretreated antigen-presenting cells.Oncol Res. 1996; 8:399–407.PubMedGoogle Scholar
  3. 3.
    Nakagawa R, Motoki K, Ueno H, et al. Treatment of hepatic metastasis of the colon 26 adenocarcinoma with an α-galactosylceramide, KRN7000.Cancer Res. 1998;58:1202–1207.PubMedGoogle Scholar
  4. 4.
    Kawano T, Cui J, Koezuka Y, et al. CD1d-restricted and TCR-mediated activation of Vα14 NKT cells by glycosylceramides.Science. 1997;278:1626–1629.PubMedCrossRefGoogle Scholar
  5. 5.
    Phase I in cancer Patients, Netherlands Study: H. Pinedo et. al in press.Google Scholar
  6. 6.
    Luc van Kaer, et al.Nature Med. 2001;7:1052.PubMedCrossRefGoogle Scholar
  7. 7.
    Jean Francois Bach, et al.,Nature Med. 2001;7:1057.PubMedCrossRefGoogle Scholar
  8. 8.
    Luc. Van Kaer, et al.J. Exp Med. 2001.Google Scholar
  9. 9.
    Kakimi K, et al.J Exp Med. 2000;192:921.PubMedCrossRefGoogle Scholar
  10. 10.
    Gonzalez G, et al.PNAS. 2000;97:8461.CrossRefGoogle Scholar
  11. 11.
    Carnaud C, et al.J. Immunology. 1999;63:4647.Google Scholar
  12. 12.
    van der Villet H, et al.J Imm Method. 2001;247:61.CrossRefGoogle Scholar
  13. 13.
    Nishi N, et al.Human Immunology. 2000.Google Scholar
  14. 14.
    Godfrey D, et al.Immunology Today. 2000;21:573.PubMedCrossRefGoogle Scholar
  15. 15.
    Pinedo H, et al. In press.Google Scholar
  16. 16.
    van der Villet H, et al.Clin. Immunology. 2001;100:144.CrossRefGoogle Scholar
  17. 17.
    Pinedo H, et al. in press.Google Scholar
  18. 18.
    van der Villet H, et. al.J Immunology. 2001.Google Scholar
  19. 19.
    Nishi N, et al.Nature Immunology. 2000;1:459.CrossRefGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2002

Authors and Affiliations

  • Akihiro Shimosaka
    • 1
  1. 1.Pharmaceutical DivisionKirin Brewery Co., Ltd.Japan

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