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West Ashley Library
9 a.m. – 7 p.m.
Phone: (843) 766-6635
Main Library
9 a.m. - 8 p.m.
Phone: (843) 805-6930
Folly Beach Library
Closed for renovations
Phone: (843) 588-2001
John L. Dart Library
9 a.m. – 7 p.m.
Phone: (843) 722-7550
St. Paul's/Hollywood Library
9 a.m. - 8 p.m.
Phone: (843) 889-3300
Mt. Pleasant Library
9 a.m. – 8 p.m.
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Dorchester Road Library
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Edgar Allan Poe/Sullivan's Island Library
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John's Island Library
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Edisto Library
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Wando Mount Pleasant Library
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Phone: (843) 884-9741
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The Type II Anti‐CD20 Antibody Obinutuzumab (GA101) Is More Effective Than Rituximab at Depleting B Cells and Treating Disease in a Murine Lupus Model.
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- Author(s): Marinov, Anthony D.; Wang, Haowei; Bastacky, Sheldon I.; Puijenbroek, Erwin; Schindler, Thomas; Speziale, Dario; Perro, Mario; Klein, Christian; Nickerson, Kevin M.; Shlomchik, Mark J.
- Source:
Arthritis & Rheumatology; May2021, Vol. 73 Issue 5, p826-836, 11p- Subject Terms:
- Source:
- Additional Information
- Abstract: Objective: Depleting pathogenic B cells could treat systemic lupus erythematosus (SLE). However, depleting B cells in an inflammatory setting such as lupus is difficult. This study was undertaken to investigate whether a type II anti‐CD20 monoclonal antibody (mAb) with a different mechanism of action, obinutuzumab (GA101), is more effective than a type I anti‐CD20 mAb, rituximab (RTX), in B cell depletion in lupus, and whether efficient B cell depletion results in amelioration of disease. Methods: We treated lupus‐prone MRL/lpr mice expressing human CD20 on B cells (hCD20 MRL/lpr mice) with either RTX or GA101 and measured B cell depletion under various conditions, as well as multiple clinical end points. Results: A single dose of GA101 was markedly more effective than RTX in depleting B cells in diseased MRL/lpr mice (P < 0.05). RTX overcame resistance to B cell depletion in diseased MRL/lpr mice with continuous treatments. GA101 was more effective in treating hCD20 MRL/lpr mice with early disease, as GA101‐treated mice had reduced glomerulonephritis (P < 0.05), lower anti‐RNA autoantibody titers (P < 0.05), and fewer activated CD4+ T cells (P < 0.0001) compared to RTX‐treated mice. GA101 also treated advanced disease, and continual treatment prolonged survival. Using variants of GA101, we also elucidated B cell depletion mechanisms in vivo in mice with lupus. Conclusion: Albeit both anti‐CD20 antibodies ameliorated early disease, GA101 was more effective than RTX in important parameters, such as glomerulonephritis score. GA101 proved beneficial in an advanced disease model, where it prolonged survival. These data support clinical testing of GA101 in SLE and lupus nephritis. [ABSTRACT FROM AUTHOR]
- Abstract: Copyright of Arthritis & Rheumatology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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