Title :

Solubilization of α-galactosylceramide in aqueous medium: Impact on Natural Killer T cell activation and antitumor responses

Author(s) :

Macho-Fernandez, Elodie [Auteur]
Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Chekkat, Neila [Auteur]
Conception et application de molécules bioactives [CAMB]
Ehret, Christophe [Auteur]
Conception et application de molécules bioactives [CAMB]
Thomann, Jean-Sébastien [Auteur]
Conception et application de molécules bioactives [CAMB]
de Giorgi, Marcella [Auteur]
Conception et application de molécules bioactives [CAMB]
Spanedda, Maria Vittoria [Auteur]
Conception et application de molécules bioactives [CAMB]
Bourel-Bonnet, Line [Auteur]
Conception et application de molécules bioactives [CAMB]
Betbeder, Didier [Auteur]
Université d'Artois [UA]
Lille Inflammation Research International Center - U 995 [LIRIC]
Heurtault, Béatrice [Auteur]
Conception et application de molécules bioactives [CAMB]
Faveeuw, Christelle [Auteur]
Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]
Fournel, Sylvie [Auteur correspondant]
Conception et application de molécules bioactives [CAMB]
Frisch, Benoit [Auteur]
Conception et application de molécules bioactives [CAMB]
Trottein, Francois [Auteur]
Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Journal title :

International Journal of Pharmaceutics

Pages :

354-363

Publisher :

Elsevier

Publication date :

2017-09

ISSN :

0378-5173

English keyword(s) :

Water-soluble α-GalCer
Micelles
Liposomes
Cancer
iNKT
α-GalCer formulations

HAL domain(s) :

Sciences du Vivant [q-bio]/Cancer
Sciences du Vivant [q-bio]/Immunologie/Immunité adaptative
Sciences du Vivant [q-bio]/Immunologie/Vaccinologie

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 >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Centre d'Infection et d'Immunité de Lille (CIIL) - U1019 - UMR 9017

Source :

Harvested from HAL