دورية أكاديمية
أعرض في EDS

Complement deficiencies limit CD20 monoclonal antibody treatment efficacy in CLL.

التفاصيل البيبلوغرافية
العنوان: Complement deficiencies limit CD20 monoclonal antibody treatment efficacy in CLL.
المؤلفون: Middleton O; Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK., Cosimo E; Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK., Dobbin E; Department of Haematology, Western General Hospital, Edinburgh, UK., McCaig AM; 1] Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK [2] Department of Haematology, Royal Alexandra Hospital, Paisley, UK., Clarke C; GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex, UK., Brant AM; GlaxoSmithKline UK Ltd, Stockley Park West, Uxbridge, Middlesex, UK., Leach MT; Department of Haematology, West of Scotland Cancer Centre, Gartnavel General Hospital, Glasgow, UK., Michie AM; Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK., Wheadon H; Paul O'Gorman Leukaemia Research Centre, Institute of Cancer Sciences, College of Medicine, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
المصدر: Leukemia [Leukemia] 2015 Jan; Vol. 29 (1), pp. 107-14. Date of Electronic Publication: 2014 May 02.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group, Specialist Journals Country of Publication: England NLM ID: 8704895 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5551 (Electronic) Linking ISSN: 08876924 NLM ISO Abbreviation: Leukemia Subsets: MEDLINE
أسماء مطبوعة: Publication: 2000- : London : Nature Publishing Group, Specialist Journals
Original Publication: [Baltimore, Md.] : Williams & Wilkins, [c1987-
مواضيع طبية MeSH: Antibodies, Monoclonal/*therapeutic use , Antigens, CD20/*immunology , Complement System Proteins/*deficiency , Leukemia, Lymphocytic, Chronic, B-Cell/*therapy, Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal, Humanized ; Cells, Cultured ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/blood
مستخلص: Monoclonal antibodies (MAbs) form a central part of chronic lymphocytic leukaemia (CLL) treatment. We therefore evaluated whether complement defects in CLL patients reduced the induction of complement-dependent cytotoxicity (CDC) by using anti-CD20 MAbs rituximab (RTX) and ofatumumab (OFA). Ofatumumab elicited higher CDC levels than RTX in all CLL samples examined, particularly in poor prognosis cohorts (11q- and 17p-). Serum sample analyses revealed that 38.1% of patients were deficient in one or more complement components, correlating with reduced CDC responses. Although a proportion of patients with deficient complement levels initially induced high levels of CDC, on secondary challenge CDC activity in sera was significantly reduced, compared with that in normal human serum (NHS; P<0.01; n=52). In addition, a high CLL cell number contributed to rapid complement exhaustion. Supplementing CLL serum with NHS or individual complement components, particularly C2, restored CDC on secondary challenge to NHS levels (P<0.0001; n=9). In vivo studies revealed that complement components were exhausted in CLL patient sera post RTX treatment, correlating with an inability to elicit CDC. Supplementing MAb treatment with fresh-frozen plasma may therefore maintain CDC levels in CLL patients with a complement deficiency or high white blood cell count. This study has important implications for CLL patients receiving anti-CD20 MAb therapy.
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معلومات مُعتمدة: G0701354 United Kingdom MRC_ Medical Research Council
المشرفين على المادة: 0 (Antibodies, Monoclonal)
0 (Antibodies, Monoclonal, Humanized)
0 (Antigens, CD20)
9007-36-7 (Complement System Proteins)
M95KG522R0 (ofatumumab)
تواريخ الأحداث: Date Created: 20140503 Date Completed: 20150324 Latest Revision: 20220129
رمز التحديث: 20231215
DOI: 10.1038/leu.2014.146
PMID: 24787488
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5551
DOI:10.1038/leu.2014.146