PMID: 11921052Mar 29, 2002Paper

Antibody-mediated suppression of Vbeta5.2/5.3(+) T cells in multiple sclerosis: results from an MRI-monitored phase II clinical trial

Annals of Neurology
Joep KillesteinC H Polman

Abstract

The objective of this study was to evaluate the safety and efficacy of the humanized antibody ATM-027 in a baseline versus treatment magnetic resonance imaging-monitored study. Expansion of Vbeta5.2/5.3(+) T cells has been demonstrated in the peripheral blood, cerebrospinal fluid, and brain lesions of MS patients. In a phase I study, ATM-027 depleted these cells in peripheral blood and, in parallel, T-cell MBP reactivity and IFN-gamma expression were reduced. We studied 59 patients with relapsing-remitting MS (47 on ATM-027 and 12 on placebo) stratified for HLA-DR2 status. Monthly intravenous injections were given for 6 months. Individual dose titration was employed to obtain depletion of the target T-cell level and downregulation of antigen receptor density as monitored by flow cytometry. Five monthly magnetic resonance imaging scans were performed before treatment to establish baseline activity, six during treatment, and three during follow-up. Additional immunological assessments were performed to elucidate the mechanism of action of ATM-027. The treatment was safe and well tolerated, inducing consistent suppression of the target cell population. During run-in, active lesions were found in 78.7% (37/47) of patients treated w...Continue Reading

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Citations

Aug 26, 2006·Nature Clinical Practice. Neurology·Reinhard Hohlfeld, Hartmut Wekerle
Mar 5, 2011·British Journal of Pharmacology·Cris S ConstantinescuBruno Gran
Apr 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yoh MatsumotoYasuto Itoyama
Jan 22, 2005·Annual Review of Medicine·Jingwu Zhang, George Hutton
Oct 4, 2002·The New England Journal of Medicine·Joep Killestein
Mar 18, 2005·Annual Review of Immunology·Mireia Sospedra, Roland Martin
Dec 7, 2011·Nature Reviews. Neurology·Frederik BarkhofMassimo Filippi
Aug 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Reinhard Hohlfeld, Hartmut Wekerle
Feb 22, 2003·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Stephen R RobinsonGerald Münch
Jul 21, 2004·Journal of the Neurological Sciences·R E Gonsette

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