Lipidic Aminoglycoside Derivatives: A New Class of Immunomodulators Inducing a Potent Innate Immune Stimulation
Abstract: 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.
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Erschienen in
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Lipidic Aminoglycoside Derivatives: A New Class of Immunomodulators Inducing a Potent Innate Immune Stimulation ; volume:6 ; number:16 ; year:2019 ; extent:13
Advanced science ; 6, Heft 16 (2019) (gesamt 13)
- Urheber
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Colombani, Thibault
Haudebourg, Thomas
Decossas, Marion
Lambert, Olivier
Ada Da Silva, Grace
Altare, Frederic
Pitard, Bruno
- DOI
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10.1002/advs.201900288
- URN
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urn:nbn:de:101:1-2022080307281508724280
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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15.08.2025, 07:25 MESZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Colombani, Thibault
- Haudebourg, Thomas
- Decossas, Marion
- Lambert, Olivier
- Ada Da Silva, Grace
- Altare, Frederic
- Pitard, Bruno
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