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

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Non-glycosidic compounds can stimulate both human and mouse iNKT cells. / Jukes, John-Paul; Gileadi, Uzi; Ghadbane, Hemza; Yu, Ting-Fong; Shepherd, Dawn; Cox, Liam R; Besra, Gurdyal S; Cerundolo, Vincenzo.

In: European Journal of Immunology, 13.02.2016.

Research output: Contribution to journalArticlepeer-review

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Jukes, John-Paul ; Gileadi, Uzi ; Ghadbane, Hemza ; Yu, Ting-Fong ; Shepherd, Dawn ; Cox, Liam R ; Besra, Gurdyal S ; Cerundolo, Vincenzo. / Non-glycosidic compounds can stimulate both human and mouse iNKT cells. In: European Journal of Immunology. 2016.

Bibtex

@article{d7b3e1cbe3ad49a68ad2c8d56835b4a0,
title = "Non-glycosidic compounds can stimulate both human and mouse iNKT cells",
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.",
keywords = "α-Galactosylceramide, CD1d, Immunotherapy, iNKT cell, Tumor",
author = "John-Paul Jukes and Uzi Gileadi and Hemza Ghadbane and Ting-Fong Yu and Dawn Shepherd and Cox, {Liam R} and Besra, {Gurdyal S} and Vincenzo Cerundolo",
note = "This article is protected by copyright. All rights reserved.",
year = "2016",
month = feb,
day = "13",
doi = "10.1002/eji.201546114",
language = "English",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",

}

RIS

TY - JOUR

T1 - Non-glycosidic compounds can stimulate both human and mouse iNKT cells

AU - Jukes, John-Paul

AU - Gileadi, Uzi

AU - Ghadbane, Hemza

AU - Yu, Ting-Fong

AU - Shepherd, Dawn

AU - Cox, Liam R

AU - Besra, Gurdyal S

AU - Cerundolo, Vincenzo

N1 - This article is protected by copyright. All rights reserved.

PY - 2016/2/13

Y1 - 2016/2/13

N2 - 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.

AB - 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.

KW - α-Galactosylceramide

KW - CD1d

KW - Immunotherapy

KW - iNKT cell

KW - Tumor

U2 - 10.1002/eji.201546114

DO - 10.1002/eji.201546114

M3 - Article

C2 - 26873393

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

ER -