Measurement of serum levels of natalizumab, an immunoglobulin G4 therapeutic monoclonal antibody
| Autor: | Rob C. Aalberse, Lucien A. Aarden, Joep Killestein, Astrid van Leeuwen, Anke Vennegoor, Gerrit Jan Wolbink, Theo Rispens |
|---|---|
| Přispěvatelé: | Neurology, CCA - Immuno-pathogenesis, NCA - Multiple Sclerosis and Other Neuroinflammatory Diseases, Landsteiner Laboratory |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Multiple Sclerosis
medicine.drug_class Biophysics Enzyme-Linked Immunosorbent Assay Antibodies Monoclonal Humanized Monoclonal antibody Biochemistry Subclass law.invention Natalizumab In vivo law parasitic diseases medicine Animals Humans Molecular Biology integumentary system biology Chemistry Multiple sclerosis fungi Antibodies Monoclonal Cell Biology medicine.disease In vitro Immunoglobulin Fc Fragments Immunoglobulin G Immunology biology.protein Recombinant DNA Rabbits Antibody Protein Binding medicine.drug |
| Zdroj: | Rispens, T, van Leeuwen, A, Vennegoor, A, Killestein, J, Aalberse, R C, Wolbink, G J & Aarden, L A 2011, ' Measurement of serum levels of natalizumab, an immunoglobulin G4 therapeutic monoclonal antibody ', Analytical Biochemistry, vol. 411, no. 2, pp. 271-276 . https://doi.org/10.1016/j.ab.2011.01.001 Analytical Biochemistry, 411(2), 271-276. Academic Press Inc. Analytical biochemistry, 411(2), 271-276. Academic Press Inc. |
| ISSN: | 0003-2697 |
| DOI: | 10.1016/j.ab.2011.01.001 |
| Popis: | Human immunoglobulin G4 (IgG4) is a poor trigger of effector functions and, therefore, is the preferred subclass for therapeutic monoclonal antibodies that merely aim to block their in vivo targets. An example is natalizumab, a recombinant IgG4 antibody directed against alpha 4-integrin and used for treatment of multiple sclerosis. Efficient treatment requires that the pharmacokinetics of therapeutic monoclonal antibodies can be accurately monitored. For natalizumab, this requires special precautions due to recently reported structural peculiarities of human IgG4. Here we describe the development of an assay to determine serum levels of natalizumab. Compared with other IgG subclasses, human IgG4 possesses unique structural properties that influence its interactions in both in vivo and in vitro settings. Thus. IgG4 undergoes Fab arm exchange in vivo, resulting in effectively monovalent antibodies. Furthermore, IgG4 is able to bind to other human and nonhuman IgG via Fc interactions. We demonstrate how these features can interfere with measurement of specific IgG4 and describe how we addressed these issues, resulting in an assay that is not sensitive to Fab arm exchange by natalizumab or to IgG4 Fc interactions. (C) 2011 Elsevier Inc. All rights reserved |
| Databáze: | OpenAIRE |
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