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α-Galactosylceramide (α-GalCer, KRN7000) is a synthetic glycolipid derived from structure-activity relationship studies of galactosylceramides isolated from the marine sponge Agelas mauritianus. α-GalCer is a strong immunostimulant and shows potent anti-tumour activity in many in vivo models.[1]

Immunostimulatory properties

α-GalCer is a potent activator of iNKT cells, and a model CD1d antigen. The invariant T cell receptor of the iNKT cell is able to bind the CD1d:glycolipid complex leading to iNKT cell activation in both mice and humans.[2]

Adjuvant activity

In combination with a peptide antigen, α-GalCer is able to stimulate a strong immune response against the epitope. The CD1d:glycolipid:TCR interaction activates the iNKT cell which can then activate the dendritic cell. This causes the release of a range of cytokines and licenses the dendritic cell to activate a peptide-specific T cell response. This adjuvant acts through this cellular interaction, rather than through classic pattern recognition receptor pathways.[3]

References

  1. ^ Morita, Masahiro; Motoki, Kazuhiro; Akimoto, Kohji; Natori, Takenori; Sakai, Teruyuki; Sawa, Eiji; Yamaji, Kazuo; Koezuka, Yasuhiko; Kobayashi, Eiichi (1995-06-01). "Structure-Activity Relationship of .alpha.-Galactosylceramides against B16-Bearing Mice". Journal of Medicinal Chemistry. 38 (12): 2176–2187. doi:10.1021/jm00012a018. ISSN 0022-2623. PMID 7783149.
  2. ^ Godfrey, Dale I.; Kronenberg, Mitchell (2004-11-15). "Going both ways: Immune regulation via CD1d-dependent NKT cells". Journal of Clinical Investigation. 114 (10): 1379–1388. doi:10.1172/jci200423594. ISSN 0021-9738. PMC 525753. PMID 15545985.
  3. ^ Cerundolo, Vincenzo; Silk, Jonathan D.; Masri, S. Hajar; Salio, Mariolina (January 2009). "Harnessing invariant NKT cells in vaccination strategies". Nature Reviews Immunology. 9 (1): 28–38. doi:10.1038/nri2451. ISSN 1474-1741. PMID 19079136. S2CID 38675164.
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