Development and validation of a targeted affinity-enrichment and LC-MS/MS proteomics approach for the therapeutic monitoring of adalimumab.

作者: Yifei Yang , Emily Wysocki , Kwasi Antwi , Eric Niederkofler , Edward K.Y. Leung

DOI: 10.1016/J.CCA.2018.05.015

关键词: Tumor necrosis factor alphaRheumatoid arthritisPharmacologyTherapeutic effectDrugAdalimumabAntibodyProteomicsMonoclonal antibodyMedicine

摘要: Abstract Background The anti-tumor necrosis factor alpha (TNFα) therapeutic monoclonal antibodies (mAbs), such as adalimumab, are widely used in the treatment of rheumatoid arthritis, inflammatory bowel diseases, and other auto-immune diseases. administration adalimumab can elicit immune responses from some patients, resulting formation anti-drug (ADAbs). ADAbs diminish effects by neutralizing TNFα binding site or increasing its clearance circulation. Methods To effectively monitor concentrations we developed validated a targeted quantitative proteomic assay to determine circulating adalimumab. Since drug be attenuated ADAbs, method adopted an affinity-enrichment step selectively quantify bioavailable forms patient serum samples. Results performance LC–MS/MS based provides analytical measuring range precisions applicable for monitoring It also comparable results cell-based activity when evaluating samples with different Conclusion Our both sub-therapeutic This design alternative isotope-labeled peptides approach currently proteomics methods.

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