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

Autor: Macho-Fernandez E; Univ. Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59000 Lille, France; Institut National de la Santé et de la Recherche Médicale U1019, F-59000 Lille, France; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France; Institut Pasteur de Lille, F-59000 Lille, France., Chekkat N; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France., Ehret C; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France., Thomann JS; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France., De Giorgi M; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France., Spanedda MV; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France., Bourel-Bonnet L; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France., Betbeder D; LIRIC - UMR 995 Inserm/Université Lille 2/CHRU Lille, F-59045 Lille Cedex, France; Université d'Artois, 62000 Arras, France., Heurtault B; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France. Electronic address: bheurtault@unistra.fr., Faveeuw C; Univ. Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59000 Lille, France; Institut National de la Santé et de la Recherche Médicale U1019, F-59000 Lille, France; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France; Institut Pasteur de Lille, F-59000 Lille, France., Fournel S; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France. Electronic address: s.fournel@unistra.fr., Frisch B; Université de Strasbourg, CNRS, CAMB UMR 7199, 67000 Strasbourg, France., Trottein F; Univ. Lille, U1019 - UMR 8204 - CIIL - Centre d'Infection et d'Immunité de Lille, F-59000 Lille, France; Centre National de la Recherche Scientifique, UMR 8204, F-59000 Lille, France; Institut National de la Santé et de la Recherche Médicale U1019, F-59000 Lille, France; Centre Hospitalier Universitaire de Lille, F-59000 Lille, France; Institut Pasteur de Lille, F-59000 Lille, France.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2017 Sep 15; Vol. 530 (1-2), pp. 354-363. Date of Electronic Publication: 2017 Jul 22.
DOI: 10.1016/j.ijpharm.2017.07.054
Abstrakt: 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.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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