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

Details

Serval ID
serval:BIB_95E41673F9CE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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
Journal
Journal of Immunology
Author(s)
Guex-Crosier  Y., Raber  J., Chan  C. C., Kriete  M. S., Benichou  J., Pilson  R. S., Kerwin  J. A., Waldmann  T. A., Hakimi  J., Roberge  F. G.
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
01/1997
Volume
158
Number
1
Pages
452-8
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jan 1
Abstract
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.
Keywords
Animals Antibodies, Monoclonal/*immunology Autoimmune Diseases/*immunology Cells, Cultured Disease Models, Animal Haplorhini Humans Lymphocyte Activation Peptide Fragments/*immunology Receptors, Interleukin-15 Receptors, Interleukin-2/*immunology Recombinant Fusion Proteins/*immunology Uveitis/*immunology/prevention & control
Pubmed
Web of science
Create date
28/01/2008 12:45
Last modification date
20/08/2019 14:58
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