Lipidic Aminoglycoside Derivatives: A New Class of Immunomodulators Inducing a Potent Innate Immune Stimulation
| dc.rights.license | open | en_US |
| dc.contributor.author | COLOMBANI, T. | |
| dc.contributor.author | HAUDEBOURG, T. | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | DECOSSAS, M. | |
| hal.structure.identifier | Chimie et Biologie des Membranes et des Nanoobjets [CBMN] | |
| dc.contributor.author | LAMBERT, O. | |
| dc.contributor.author | DA SILVA, G. A. | |
| dc.contributor.author | ALTARE, F. | |
| dc.contributor.author | PITARD, B. | |
| dc.date.accessioned | 2020-06-11T15:52:53Z | |
| dc.date.available | 2020-06-11T15:52:53Z | |
| dc.date.issued | 2019 | |
| dc.identifier.issn | 2198-3844 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/7894 | |
| dc.description.abstractEn | Development of simple and fully characterized immunomodulatory molecules is an active area of research to enhance current immunotherapies. Monophosphoryl lipid A (MPL), a nontoxic lipidic derivative from bacteria, is the first and currently only adjuvant approved in humans. However, its capacity to induce a potent response against weak immunogenic tumoral-associated antigens remains limited. Herein, a new generation of lipidic immunomodulators to conduct a structure-activity relationship study to determine the minimal structural elements conferring immunomodulatory properties is introduced. Two lead molecules characterized by a short succinyl linker between two oleyl chains and a polar headgroup consisting of either naturally occurring tobramycin (DOST) or kanamycin (DOSK) are identified. These two lipoaminoglycosides self-assemble in very small vesicles. In a wide variety of cells including 3D human cell culture, DOST and DOSK induce the upregulation of proinflammatory cytokines and interferon-inducible proteins in a dose and time-dependent manner via a caveolae-dependent proinflammatory mechanism and phosphatidylinositol phospholipase C activation. Furthermore, after intratumoral administration, these lipoaminoglycosides induce an efficient immune response leading to significant antitumor activity in a mouse breast cancer model. Altogether, these findings indicate that DOST and DOSK are two groundbreaking synthetic lipid immunostimulators that can be used as adjuvants to enhance current immunotherapeutic treatments. | |
| dc.description.sponsorship | CESTI (TSI-IHU) - ANR-10-IBHU-0005 | en_US |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-ShareAlike 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/3.0/us/ | * |
| dc.subject.en | adjuvants | |
| dc.subject.en | cationic lipids | |
| dc.subject.en | immunotherapy | |
| dc.subject.en | lipoaminoglycosides | |
| dc.subject.en | phosphatidylinositol phospholipase C (PLC) | |
| dc.title.en | Lipidic Aminoglycoside Derivatives: A New Class of Immunomodulators Inducing a Potent Innate Immune Stimulation | |
| dc.title.alternative | Adv.Sci. | en_US |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1002/advs.201900288 | |
| dc.subject.hal | Chimie/Matériaux | en_US |
| bordeaux.journal | Advanced Science | en_US |
| bordeaux.volume | 6 | en_US |
| bordeaux.hal.laboratories | Institut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248 | en_US |
| bordeaux.issue | 16 | en_US |
| bordeaux.institution | Bordeaux INP | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.identifier | hal-03182134 | |
| hal.version | 1 | |
| hal.date.transferred | 2021-03-26T09:46:21Z | |
| hal.export | true | |
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