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

Research output: Contribution to journalArticlepeer-review

Authors

  • John-Paul Jukes
  • Uzi Gileadi
  • Hemza Ghadbane
  • Ting-Fong Yu
  • Dawn Shepherd
  • Vincenzo Cerundolo

Colleges, School and Institutes

Abstract

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.

Details

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

Keywords

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