Titre
Molecular and therapeutic characterization of anti-ectodysplasin A receptor (EDAR) agonist monoclonal antibodies.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Kowalczyk, C.
Auteure/Auteur
Dunkel, N.
Auteure/Auteur
Willen, L.
Auteure/Auteur
Casal, M.L.
Auteure/Auteur
Mauldin, E.A.
Auteure/Auteur
Gaide, O.
Auteure/Auteur
Tardivel, A.
Auteure/Auteur
Badic, G.
Auteure/Auteur
Etter, A.L.
Auteure/Auteur
Favre, M.
Auteure/Auteur
Jefferson, D.M.
Auteure/Auteur
Headon, D.J.
Auteure/Auteur
Demotz, S.
Auteure/Auteur
Schneider, P.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1083-351X
Statut éditorial
Publié
Date de publication
2011
Volume
286
Numéro
35
Première page
30769
Dernière page/numéro d’article
30779
Langue
anglais
Résumé
The TNF family ligand ectodysplasin A (EDA) and its receptor EDAR are required for proper development of skin appendages such as hair, teeth, and eccrine sweat glands. Loss of function mutations in the Eda gene cause X-linked hypohidrotic ectodermal dysplasia (XLHED), a condition that can be ameliorated in mice and dogs by timely administration of recombinant EDA. In this study, several agonist anti-EDAR monoclonal antibodies were generated that cross-react with the extracellular domains of human, dog, rat, mouse, and chicken EDAR. Their half-life in adult mice was about 11 days. They induced tail hair and sweat gland formation when administered to newborn EDA-deficient Tabby mice, with an EC(50) of 0.1 to 0.7 mg/kg. Divalency was necessary and sufficient for this therapeutic activity. Only some antibodies were also agonists in an in vitro surrogate activity assay based on the activation of the apoptotic Fas pathway. Activity in this assay correlated with small dissociation constants. When administered in utero in mice or at birth in dogs, agonist antibodies reverted several ectodermal dysplasia features, including tooth morphology. These antibodies are therefore predicted to efficiently trigger EDAR signaling in many vertebrate species and will be particularly suited for long term treatments.
Sujets
PID Serval
serval:BIB_9E190030D736
PMID
Open Access
Oui
Date de création
2011-10-26T11:22:03.071Z
Date de création dans IRIS
2025-05-21T02:17:06Z
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Nom
5_21730053_Postprint.pdf
Version du manuscrit
postprint
Taille
4.87 MB
Format
Adobe PDF
PID Serval
serval:BIB_9E190030D736.P001
URN
urn:nbn:ch:serval-BIB_9E190030D7360
Somme de contrôle
(MD5):0e4491f1cf6dcdda611276987ca1f365