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

作者：Yang Yifei^*; Wysocki Emily; Antwi Kwasi; Niederkofler Eric; Leung Edward K Y; Lazar Molnar Eszter; Yeo Kiang Teck J

来源：Clinica Chimica Acta, 2018, 483: 308-314.

DOI：10.1016/j.cca.2018.05.015

• Bioavailable adalimumab
• Anti-drug antibodies
• Quantitative and targeted proteomics

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

• 出版日期2018-8