Model for predicting age-dependent safety and immunomodulatory effects of STING ligands in non-human primates
| dc.rights.license | open | en_US |
| dc.contributor.author | TAKAHAMA, Shokichi | |
| dc.contributor.author | ISHIGE, Kazuya | |
| dc.contributor.author | NOGIMORI, Takuto | |
| dc.contributor.author | YASUTOMI, Yasuhiro | |
| hal.structure.identifier | Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept] | |
| dc.contributor.author | APPAY, Victor | |
| dc.contributor.author | YAMAMOTO, Takuya | |
| dc.date.accessioned | 2024-08-29T08:37:59Z | |
| dc.date.available | 2024-08-29T08:37:59Z | |
| dc.date.issued | 2023 | |
| dc.identifier.issn | 2329-0501 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/201348 | |
| dc.description.abstractEn | Stimulator of interferon genes (STING) is a cytoplasmic dinucleotide sensor used as an immunomodulatory agent for cancer treatment. The efficacy of the STING ligand (STING-L) against various tumors has been evaluated in mouse models; however, its safety and efficacy in non-human primates have not been reported. We examined the effects of escalating doses of cyclic-di-adenosine monophosphate (c-di-AMP) or cyclic [G (3′,5′)pA (3′,5′p] (3′-3′-cGAMP) administered intramuscularly or intravenously to cynomolgus macaques. Both ligands induced transient local and systemic inflammatory responses and systemic immunomodulatory responses, including the upregulation of interferon-α (IFN-α) and IFN-γ expression and the activation of multiple immunocompetent cell subsets. Better immunological responses were observed in animals that received c-di-AMP compared with those that received 3′-3′-cGAMP. Multi-parameter analysis using a dataset obtained before administering the ligands predicted the efficacy outcome partially. Importantly, the efficacy of these ligands was reduced in older macaques. We propose that 0.5 mg/kg c-di-AMP via intramuscular administration should be the optimal starting point for clinical studies. Our study is the first to demonstrate the age-dependent safety and efficacy of STING-L in non-human primates and supports the potential of STING-L use as a direct immunomodulator in vivo. © 2022 The Author(s) | |
| dc.language.iso | EN | en_US |
| dc.rights | Attribution-NonCommercial-NoDerivs 3.0 United States | * |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/us/ | * |
| dc.subject.en | STING ligands | |
| dc.subject.en | Non-human primate | |
| dc.subject.en | Aging | |
| dc.subject.en | Flow cytometry | |
| dc.subject.en | Innate immunity | |
| dc.subject.en | Prediction | |
| dc.title.en | Model for predicting age-dependent safety and immunomodulatory effects of STING ligands in non-human primates | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1016/j.omtm.2022.12.008 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Immunologie | en_US |
| dc.identifier.pubmed | 36620070 | en_US |
| bordeaux.journal | Molecular Therapy Methods and Clinical Development | en_US |
| bordeaux.page | 99-115 | en_US |
| bordeaux.volume | 28 | en_US |
| bordeaux.hal.laboratories | ImmunoConcEpT - UMR 5164 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.institution | CNRS | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
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| hal.popular | non | en_US |
| hal.audience | Internationale | en_US |
| hal.export | true | |
| dc.rights.cc | CC BY-NC-ND | en_US |
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