Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor
| العنوان: | Generation and characterization of tabalumab, a human monoclonal antibody that neutralizes both soluble and membrane-bound B-cell activating factor |
|---|---|
| المؤلفون: | Joseph Manetta, Niles Fox, Holly A. Bina, Paul J. Ryan, Kristine Kay Kikly, Derrick R. Witcher |
| المصدر: | Journal of Inflammation Research |
| بيانات النشر: | Dove Press, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | medicine.drug_class, Immunology, Monoclonal antibody, medicine.disease_cause, Immunoglobulin secretion, Autoimmunity, B-cell malignancies, stomatognathic system, immune system diseases, hemic and lymphatic diseases, medicine, Immunology and Allergy, B-cell activating factor, Receptor, skin and connective tissue diseases, Original Research, biology, business.industry, autoimmunity, B-cell survival factor, In vitro, Tabalumab, stomatognathic diseases, biology.protein, BAFF, Antibody, business, Journal of Inflammation Research |
| الوصف: | Joseph Manetta, Holly Bina, Paul Ryan, Niles Fox, Derrick R Witcher, Kristine Kikly Biotechnology Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA Abstract: B-cell activating factor (BAFF) is a B-cell survival factor with a key role in B-cell homeostasis and tolerance. Dysregulated BAFF expression may contribute to autoimmune diseases or B-cell malignancies via effects on abnormal B-lymphocyte activation, proliferation, survival, and immunoglobulin secretion. Monoclonal antibodies were generated against human BAFF, characterized for species specificity and affinity, and screened for the ability to neutralize both membrane-bound and soluble BAFF. In addition, studies were undertaken to determine the relative potency of membrane-bound and soluble BAFF. Tabalumab has a high affinity for human, cynomolgus monkey, and rabbit BAFF. No binding to mouse BAFF was detected. Tabalumab was able to neutralize soluble human, cynomolgus monkey, or rabbit BAFF with equal potency. Our data demonstrate that membrane-bound BAFF can be a more potent stimulus for B-cells than soluble BAFF, and tabalumab also neutralized membrane-bound BAFF. Tabalumab prevented BAFF from binding to BAFF receptors and demonstrated pharmacodynamic effects in human BAFF transgenic mice. Tabalumab is a high-affinity human antibody with neutralizing activity against membrane-bound and soluble BAFF. Given our findings that membrane-bound BAFF can have greater in vitro potency than soluble BAFF, neutralization of both forms of BAFF is likely to be important for optimal therapeutic effect. Keywords: autoimmunity, B-cell malignancies, B-cell survival factor, BAFF |
| وصف الملف: | text/html |
| اللغة: | English |
| تدمد: | 1178-7031 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97b82ab1bb15d44f8737a10cd309d605 https://www.dovepress.com/generation-and-characterization-of-tabalumab-a-human-monoclonal-antibo-peer-reviewed-article-JIR |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....97b82ab1bb15d44f8737a10cd309d605 |
| قاعدة البيانات: | OpenAIRE |
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