KRN7000 mechanism

KRN7000, a glycolipid derived from the marine sponge has a novel α-galactosylceramide (α-GalCer) structure and exhibits potent anti-tumor activity by stimulating a strong immune response.  Natural Killer T Cells (NKT cells) serve as an important role regulating the immune response and in the presence of KRN7000 stimulate NKT cells to releasing a rapid production of Th1 and Th2 cytokines including IL-4, IL-10, IL-13 and IFN-gama (1,2) strongly enhancing the immune system against tumors, autoimmune diseases, viral, bacterial and parasites.  It has been experimentally determined that KRN7000 is presented by CD1d and works as a ligand to the invariant Vα 14 T cell receptor of mouse NK1.1+ Vα14Jα281β T cell receptor+ (NKT) cells (3,4) and the invariant Vα24JαQVβ11 T cell receptor of human NKT cells (5). The KRN7000 biochemical mechanism triggering the immune response has not been fully characterized and investigators continue to to understand the underlying mechanism.

Photo by Universite De Reims

Alpha-GalCer complexed with CD1d.
Graphic file from Universite De Reims

 

1) Godfrey, D. I., Hammond, K. J., Poulton, L. D., Smyth, M.J. & Baxter, A. G. (2000) Immunol. Today 21, 573-583.

2) Smyth, M. J. & Godfrey, D. I. (2000) Nat. Immunol. 1, 459-460.

3) Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kancko, Y., Sato, H., Kondo, E., Harada, M., Koseki, H., Nakayama, T., et al (1998) Proc. Natl. Acad. Sci. USA 95, 5690-5693.

4) Kawano, T., Cui, J., Koezuka, Y., Toura, I., Kaneko, Y., Motoki, K., Ueno, H., Nakagawa, R., Sato, H., Kondo, E., et al. (1997) Science 278, 1626-1629.

5) Kawano, T., Nakayama, T., Kamada, N., Kaneko, Y., Harada, M., Ogura, N., Akutsu, Y., Motohashi, S., Lizasa, T., Endo, H., et al. (1999) Cancer Res. 59, 5102-5105.

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New 7DW8-5 glycolipid

7DW8-5

Now available 7DW8-5 glycolipid derivative of Alpha-GalCer for human and mice iNKT immunoresearch

 

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December 2-6, 2017