TY - JOUR
T1 - Development and validation of a targeted affinity-enrichment and LC–MS/MS proteomics approach for the therapeutic monitoring of adalimumab
AU - Yang, Yifei
AU - Wysocki, Emily
AU - Antwi, Kwasi
AU - Niederkofler, Eric
AU - Leung, Edward K.Y.
AU - Lazar-Molnar, Eszter
AU - Yeo, Kiang Teck J.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/8
Y1 - 2018/8
N2 - 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. 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 TNFα 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.
AB - 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. 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 TNFα 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.
KW - Anti-drug antibodies
KW - Bioavailable adalimumab
KW - Quantitative and targeted proteomics
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U2 - 10.1016/j.cca.2018.05.015
DO - 10.1016/j.cca.2018.05.015
M3 - Article
C2 - 29752913
AN - SCOPUS:85047065500
SN - 0009-8981
VL - 483
SP - 308
EP - 314
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
ER -