Titre
Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Guex-Crosier, Y.
Auteure/Auteur
Raber, J.
Auteure/Auteur
Chan, C. C.
Auteure/Auteur
Kriete, M. S.
Auteure/Auteur
Benichou, J.
Auteure/Auteur
Pilson, R. S.
Auteure/Auteur
Kerwin, J. A.
Auteure/Auteur
Waldmann, T. A.
Auteure/Auteur
Hakimi, J.
Auteure/Auteur
Roberge, F. G.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0022-1767
Statut éditorial
Publié
Date de publication
1997-01
Volume
158
Numéro
1
Première page
452
Dernière page/numéro d’article
8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 1
Research Support, Non-U.S. Gov't --- Old month value: Jan 1
Résumé
We studied the efficacy and tolerance of humanized Ab interfering with the signal of the IL-2 and IL-15 receptors in a primate model of experimental autoimmune uveoretinitis. The inhibitory effects of humanized anti-Tac (HAT), an anti-IL-2R alpha-chain Ab, and HuMik beta1, an Ab directed at the beta-chain shared by the receptors of IL-2 and IL-15, were tested in culture on the proliferative response of monkey Con A-blast lymphocytes stimulated with IL-2 or IL-15. Uveitis was induced in cynomolgus monkeys by immunization with human recombinant retinal S-antigen. Treatment was initiated at the first sign of disease and consisted of HAT and HuMik beta1, alone or in combination, or vehicle control given by i.v. injection twice a week for 4 wk. Disease was evaluated by ocular funduscopy. The results in culture showed a significant dose-dependent inhibition of the IL-2-driven proliferation of lymphocytes by HAT. HuMik beta1 alone was ineffective against IL-2 stimulation, but had a marked potentiating effect in combination with HAT, independent of IL-15 signaling. IL-15-driven proliferation was inhibited by HuMik beta1, but not by HAT alone or in combination. In monkeys, experimental autoimmune uveoretinitis evolution was significantly inhibited by HAT treatment. HuMik beta1 alone had no effect on the disease. However, when used in combination, the two Ab markedly reduced the severity of ocular inflammation. The Ab were well tolerated. Only three monkeys, treated with HAT alone, made an Ab response against the injected Ab.
Sujets
PID Serval
serval:BIB_95E41673F9CE
PMID
Date de création
2008-01-28T11:45:53.475Z
Date de création dans IRIS
2025-05-21T01:14:11Z