Solubilization of alpha-galactosylceramide ...
Document type :
Article dans une revue scientifique
PMID :
Permalink :
Title :
Solubilization of alpha-galactosylceramide in aqueous medium: Impact on Natural Killer T cell activation and antitumor responses
Author(s) :
Macho-Fernandez, Elodie [Auteur]
Chekkat, Neila [Auteur]
Ehret, Christophe [Auteur]
Thomann, Jean-Sebastien [Auteur]
De Giorgi, Marcella [Auteur]
Spanedda, Maria Vittoria [Auteur]
Bourel-Bonnet, Line [Auteur]
Betbeder, Didier [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Heurtault, Beatrice [Auteur]
Faveeuw, Christelle [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Fournel, Sylvie [Auteur]
Frisch, Benoit [Auteur]
Trottein, Francois [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Chekkat, Neila [Auteur]
Ehret, Christophe [Auteur]
Thomann, Jean-Sebastien [Auteur]
De Giorgi, Marcella [Auteur]
Spanedda, Maria Vittoria [Auteur]
Bourel-Bonnet, Line [Auteur]
Betbeder, Didier [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Heurtault, Beatrice [Auteur]
Faveeuw, Christelle [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Fournel, Sylvie [Auteur]
Frisch, Benoit [Auteur]
Trottein, Francois [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Journal title :
International journal of pharmaceutics
Abbreviated title :
Int. J. Pharm.
Volume number :
530
Pages :
354-363
Publication date :
2017-09-15
ISSN :
0378-5173
English keyword(s) :
Cancer
Micelles
Water-soluble alpha-GalCer
Liposomes
alpha-GalCer formulations
iNKT
Micelles
Water-soluble alpha-GalCer
Liposomes
alpha-GalCer formulations
iNKT
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
The potent antitumor effect of α-galactosylceramide (α-GalCer) is based on its recognition by invariant Natural Killer T cells (iNKT) after its capture and presentation by antigen presenting cells including dendritic cells ...
Show more >The potent antitumor effect of α-galactosylceramide (α-GalCer) is based on its recognition by invariant Natural Killer T cells (iNKT) after its capture and presentation by antigen presenting cells including dendritic cells (DCs). Synthetic α-GalCer has already been tested in advanced cancer patients but no or only moderate clinical responses were obtained. To optimize α-GalCer efficacy, we have postulated that alternative formulations impacting its molecular organization in aqueous medium could modify DC uptake and iNKT-based immune responses. To this end, we have developed two strategies: (1) the formulation of α-GalCer in non-cationic liposomes and (2) the synthesis of a water-soluble α-GalCer analogue by anchoring a polyethyleneglycol moiety on its sugar head. The biological activities of these new preparations were compared to that induced by the classically used Polysorbate 20 α-GalCer micelles. Both formulations retained their uptake by DCs and activated iNKT cells both in vitro and in vivo. Despite a lower cytokine production, the formulations induced a potent immune response able to control lung murine carcinoma. In conclusion, it is possible to increase α-GalCer solubility in aqueous solution without limiting its antitumor properties.Show less >
Show more >The potent antitumor effect of α-galactosylceramide (α-GalCer) is based on its recognition by invariant Natural Killer T cells (iNKT) after its capture and presentation by antigen presenting cells including dendritic cells (DCs). Synthetic α-GalCer has already been tested in advanced cancer patients but no or only moderate clinical responses were obtained. To optimize α-GalCer efficacy, we have postulated that alternative formulations impacting its molecular organization in aqueous medium could modify DC uptake and iNKT-based immune responses. To this end, we have developed two strategies: (1) the formulation of α-GalCer in non-cationic liposomes and (2) the synthesis of a water-soluble α-GalCer analogue by anchoring a polyethyleneglycol moiety on its sugar head. The biological activities of these new preparations were compared to that induced by the classically used Polysorbate 20 α-GalCer micelles. Both formulations retained their uptake by DCs and activated iNKT cells both in vitro and in vivo. Despite a lower cytokine production, the formulations induced a potent immune response able to control lung murine carcinoma. In conclusion, it is possible to increase α-GalCer solubility in aqueous solution without limiting its antitumor properties.Show less >
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
CNRS
Inserm
Université de Lille
Institut Pasteur de Lille
CNRS
Inserm
Université de Lille
Institut Pasteur de Lille
Research team(s) :
Therapeutic innovation targetting inflammation
Submission date :
2019-05-17T13:14:43Z
2021-06-08T10:25:15Z
2021-06-08T10:25:15Z