Characterization and Application of a Unique Panel of Monoclonal Antibodies Generated against Etanercept
| Autor: | Nick Geukens, Kurt de Vlam, Ann Gils, Els Brouwers, Miet Peeters, Iris Detrez |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
medicine.drug_class
Immunology Enzyme-Linked Immunosorbent Assay Monoclonal antibody Severity of Illness Index Etanercept 03 medical and health sciences 0302 clinical medicine Pharmacokinetics medicine Humans Immunology and Allergy Spondylitis Ankylosing Antibodies Blocking Spondylitis Monitoring Physiologic Observer Variation 030203 arthritis & rheumatology Ankylosing spondylitis Hybridomas medicine.diagnostic_test biology Tumor Necrosis Factor-alpha business.industry Antibodies Monoclonal medicine.disease Therapeutic drug monitoring biology.protein Hybridoma technology 030211 gastroenterology & hepatology Antibody business medicine.drug |
| Zdroj: | The Journal of Immunology. 196:2879-2884 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | The clinical response in ankylosing spondylitis (AS) patients treated with biologic agents can be influenced by pharmacokinetic variability among and within these patients. Therapeutic drug monitoring is seen as a valuable tool to improve patient care. The aim of this study was to generate a panel of mAbs toward etanercept (ETN) and to determine ETN and anti-ETN concentrations in AS patients. mAbs against ETN (MA-ETN) were generated using hybridoma technology. For quantification of ETN concentrations, a mAb-based TNF-coated ELISA and a mAb/mAb-based sandwich-type ELISA were developed. For evaluation of the anti-ETN Ab response, a bridging ELISA, as well as a functional cell-based assay, were constructed. Disease activity of the AS patients was measured with the AS Disease Activity Score (ASDAS). Active disease was defined as ASDAS ≥ 2.1. A total of 59 of 76 generated mAbs were ETN specific and were characterized further. Fifty-one mAbs revealed inhibitory properties in a cell-based assay. Analysis of serum concentrations of 21 ETN-treated AS patients with the TNF/MA-ETN68C5-HRP ELISA and the MA-ETN63C8/MA-ETN61C1-HRP ELISA revealed a good Pearson’s r (+0.974) but a poor intraclass correlation coefficient (+0.528) as the result of underestimation of the values in the former ELISA. At 24 wk, ETN concentrations were similar in patients with ASDAS < 2.1 and ≥ 2.1. Anti-ETN Abs were not detected in any of the patient samples tested. In conclusion, highly sensitive mAb-based immunoassays were developed for quantification of ETN and anti-ETN concentrations. The impact of these methods needs to be evaluated further in clinical practice. |
| Databáze: | OpenAIRE |
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