Non-glycosidic compounds can stimulate both human and mouse iNKT cells

John-Paul Jukes, Uzi Gileadi, Hemza Ghadbane, Ting-Fong Yu, Dawn Shepherd, Liam R Cox, Gurdyal S Besra, Vincenzo Cerundolo

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)


Invariant natural killer T (iNKT) cells recognize CD1d/glycolipid complexes and upon activation with synthetic agonists display immunostimulatory properties. We have previously described that the non-glycosidic CD1d-binding lipid, threitolceramide (ThrCer) activates murine and human iNKT cells. Here, we show that incorporating the head-group of ThrCer into a conformationally more restricted 6- or 7-membered ring results in significantly more potent non-glycosidic analogs. In particular, ThrCer 6 was found to promote strong anti-tumor responses and to induce a more prolonged stimulation of iNKT cells than does the canonical α-galactosylceramide (α-GalCer), achieving an enhanced T-cell response at lower concentrations compared with α-GalCer both in vitro, using human iNKT-cell lines and in vivo, using C57BL/6 mice. Collectively these studies describe novel non-glycosidic ThrCer-based analogs that have improved potency in iNKT-cell activation compared with that of α-GalCer, and are clinically relevant iNKT-cell agonists. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalEuropean Journal of Immunology
Publication statusPublished - 13 Feb 2016


  • α-Galactosylceramide
  • CD1d
  • Immunotherapy
  • iNKT cell
  • Tumor


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