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Antibody-Mediated s...
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Killestein, Joep
(author)
Antibody-Mediated suppression of Vbeta5.2/5.3+ T Cells in Multiple Sclerosis : Results from an MRI-Monitored Phase II Clinical Trial
- Article/chapterEnglish2002
Publisher, publication year, extent ...
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2002-02-19
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Wiley,2002
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:liu-27837
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https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-27837URI
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https://doi.org/10.1002/ana.10146DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:1939850URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-62372URI
Supplementary language notes
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Language:English
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Summary in:English
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Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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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 Vß5.2/5.3+ 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-? 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 with ATM-027. During treatment, the median number of lesions was reduced by 33% (p = 0.13) independent of DR2 status. The corresponding volume of enhancement was 221 mm3 at baseline, with a reduction of 10% during treatment. Decreased numbers of cells expressing interferon-? messenger RNA, and decreased T-cell reactivity to several myelin antigens were found in ATM-027 treated patients. In conclusion, consistent suppression of Vß 5.2/5.3+ T cells was achieved. However, the effect size on magnetic resonance imaging was considerably less than the targeted 60%.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Olsson, TomasKarolinska Institutet
(author)
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Wallström, Erik
(author)
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Svenningsson, AndersKarolinska Institutet
(author)
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Khademi, MohsenKarolinska Institutet
(author)
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Blumhardt, Lance D
(author)
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Fagius, JanUppsala universitet,Institutionen för neurovetenskap,Neurology
(author)
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Hillert, JanKarolinska Institutet
(author)
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Landtblom, Anne-Marie,1953-Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Institutionen för nervsystem och rörelseorgan,Neurologiska kliniken(Swepub:liu)annla55
(author)
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Hedenius, Charlotte
(author)
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Årfors, Leopold
(author)
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Barkhof, Frederik
(author)
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Polman, Chris H
(author)
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Karolinska InstitutetInstitutionen för neurovetenskap
(creator_code:org_t)
Related titles
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In:Annals of Neurology: Wiley51, s. 467-0364-51341531-8249
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In:Annals of Neurology: Wiley51, s. 467-
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Killestein, Joep
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Olsson, Tomas
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Wallström, Erik
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Svenningsson, An ...
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Khademi, Mohsen
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Blumhardt, Lance ...
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Fagius, Jan
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Hillert, Jan
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Landtblom, Anne- ...
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Hedenius, Charlo ...
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Årfors, Leopold
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Barkhof, Frederi ...
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Polman, Chris H
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Annals of Neurol ...
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Linköping University
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Karolinska Institutet
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Uppsala University