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

• Published in: Clinical and experimental immunology Vol. 124; no. 1; pp. 134 - 141
• Main Authors: Brok, H. P. M., Tekoppele, J. M., Hakimi, J., Kerwin, J. A., Nijenhuis, E. M., De Groot, C. W., Bontrop, R. E., ‘t Hart, B. A.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.04.2001; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: animal model; Animals; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibody Specificity; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - pathology; Arthritis, Rheumatoid - prevention & control; Autoantibodies - blood; Autoantibodies - immunology; Autoimmune Diseases - chemically induced; Autoimmune Diseases - drug therapy; Autoimmune Diseases - pathology; Autoimmune Diseases - prevention & control; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; C-Reactive Protein - analysis; Collagen - immunology; Collagen - toxicity; Daclizumab; Disease Models, Animal; Diseases of the osteoarticular system; Drug Evaluation, Preclinical; Humans; Hydroxyproline - urine; Immunity to Infection; Immunization; Immunoglobulin G - therapeutic use; inflammation; Inflammatory joint diseases; interleukin 2 receptors; joint destruction; Macaca mulatta; Male; Medical sciences; nonhuman primate; Pharmacology. Drug treatments; Receptors, Interleukin-2 - antagonists & inhibitors; Receptors, Interleukin-2 - immunology; rheumatoid arthritis; Weight Loss; Autoimmunity; Immunopathology; Animal model; Diseases of the osteoarticular system; Monkey; Autoimmune disease; Inflammatory joint disease; Arthritis; Inflammation; Macaca mulatta; Monoclonal antibody; Biological activity; Daclizumab; Vertebrata; Chemotherapy; Chronic; Mammalia; Treatment; Animal; Collagen; Immunotherapy; Rheumatoid arthritis; Primates; Simioidea
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2001.01487.x

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 α‐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.