Suppression of ongoing disease in a nonhuman primate model of multiple sclerosis by a human-anti-human IL-12p40 antibody.
IL-12p40 is a shared subunit of two cytokines with overlapping activities in the induction of autoreactive Th1 cells and therefore a potential target of therapy in Th1-mediated diseases. We have examined whether ongoing disease in a nonhuman primate model of multiple sclerosis (MS) can be suppressed with a new human IgG1kappa Ab against human IL-12p40. Lesions developing in the brain white matter were visualized and characterized with standard magnetic resonance imaging techniques. To reflect the treatment of MS patients, treatment with the Ab was initiated after active brain white matter lesions were detected in T2-weighted images. In placebo-treated control monkeys we observed the expected progressive increase in the total T2 lesion volume and markedly increased T2 relaxation times, a magnetic resonance imaging marker of inflammation. In contrast, in monkeys treated with anti-IL-12p40 Ab, changes in the total T2 lesion volume and T2 relaxation times were significantly suppressed. Moreover, the time interval to serious neurological deficit was delayed from 31 +/- 10 to 64 +/- 20 days (odds ratio, 0.312). These results, in a disease model with high similarity to MS, are important for ongoing and planned trials of therapies that target IL-12 and/or IL-23.
't Hart
Bert A
BA
Department of Immunobiology, Biomedical Primate Research Center, Rijswijk, The Netherlands. hart@bprc.nl
Brok
Herbert P M
HP
Remarque
Ed
E
Benson
Jacqueline
J
Treacy
George
G
Amor
Sandra
S
Hintzen
Rogier Q
RQ
Laman
Jon D
JD
Bauer
Jan
J
Blezer
Erwin L A
EL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D002144:Callithrix; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology*; D053762:Interleukin-12 Subunit p40; D008279:Magnetic Resonance Imaging; D008297:Male; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D021122:Protein Subunits / Q000276:immunology*
D000911:Antibodies, Monoclonal; D053762:Interleukin-12 Subunit p40; D021122:Protein Subunits; D018664:Interleukin-12