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Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 receptor (DACLIZUMAB) on collagen-induced arthritis (CIA) in rhesus monkeys

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Author: Brok, H.P.M. · Tekoppele, J.M. · Hakimi, J. · Kerwin, J.A. · Nijenhuist, E.M. · Groot, C.W.de · Bontrop, R.E. · Hart 't, B.A.
Type:article
Date:2001
Institution: Gaubius Instituut
Source:Clinical and Experimental Immunology, 1, 124, 134-141
Identifier: 236098
doi: doi:10.1046/j.1365-2249.2001.01487.x
Keywords: Biology · Biomedical Research · Animal model · Inflammation · Joint destruction · Nonhuman primate · Rheumatoid arthritis · Collagen · Interleukin 2 receptor · Interleukin 2 receptor antibody · Monoclonal antibody · Animal experiment · Animal model · Autoimmune disease · Controlled study · Drug blood level · Drug half life · Immunization · Immunogenicity · Inflammation · Joint destruction · Male · Nonhuman · Priority journal · Prophylaxis · Rhesus monkey · Rheumatoid arthritis · Animals · Antibodies, Monoclonal · Antibody Specificity · Arthritis, Rheumatoid · Autoantibodies · Autoimmune Diseases · C-Reactive Protein · Collagen · Disease Models, Animal · Drug Evaluation, Preclinical · Humans · Hydroxyproline · Immunization · Immunoglobulin G · Macaca mulatta · Male · Receptors, Interleukin-2 · Weight Loss

Abstract

CIA in the rhesus monkey is an autoimmune-based polyarthritis with inflammation and erosion of synovial joints that shares various features with human rheumatoid arthritis (RA). The close phylogenetic relationship between man and rhesus monkey makes the model very suitable for preclinical safety and efficacy testing of new therapeutics with exclusive reactivity in primates. In this study we have investigated the prophylactic and therapeutic effects of a humanized monoclonal antibody (Daclizumab) against the a-chain of the IL-2 receptor (CD25). When Daclizumab treatment was started well after immunization but before the expected onset of CIA a significant reduction of joint-inflammation and joint-erosion was observed. A therapeutic treatment, initiated as soon as the first clinical signs of CIA were observed, proved also effective since joint-degradation was abrogated. The results of this study indicate that Daclizumab has clinical potential for the treatment of RA during periods of active inflammation and suppression of the destruction of the joint tissues.