Abstract
The expanding field of monoclonal antibody-based pharmaceuticals has triggered increased interest in analytical characterization of these large proteins and in understanding of their heterogeneity and degradation pathways. As a result, a large number of enzymatic modifications as well as chemical and physical degradations have been reported in monoclonal antibodies in recent years. Most heterogeneity is related to changes in the surface charge of the antibody, either directly, as a change in the number of charged residues, or indirectly as a chemical or physical alteration that changes surface-charge distribution. This review presents an overview of the sources of charge-related heterogeneity in monoclonal antibodies and the methods used for their detection. A detailed section is dedicated to deamidation of asparagine and isomerization of aspartic acid residues, two ubiquitous degradation pathways detected in antibodies and other proteins as well. Finally, kinetic modeling of the accumulation of antibody variants is presented as a tool to determine the expected fraction of molecules that have undergone one or more degradation reactions.
Keywords: Monoclonal antibody, charge heterogeneity, degradation, chromatography, deamidation, isomerization
Current Pharmaceutical Biotechnology
Title: Heterogeneity of Monoclonal Antibodies Revealed by Charge-Sensitive Methods
Volume: 9 Issue: 6
Author(s): J. Vlasak and R. Ionescu
Affiliation:
Keywords: Monoclonal antibody, charge heterogeneity, degradation, chromatography, deamidation, isomerization
Abstract: The expanding field of monoclonal antibody-based pharmaceuticals has triggered increased interest in analytical characterization of these large proteins and in understanding of their heterogeneity and degradation pathways. As a result, a large number of enzymatic modifications as well as chemical and physical degradations have been reported in monoclonal antibodies in recent years. Most heterogeneity is related to changes in the surface charge of the antibody, either directly, as a change in the number of charged residues, or indirectly as a chemical or physical alteration that changes surface-charge distribution. This review presents an overview of the sources of charge-related heterogeneity in monoclonal antibodies and the methods used for their detection. A detailed section is dedicated to deamidation of asparagine and isomerization of aspartic acid residues, two ubiquitous degradation pathways detected in antibodies and other proteins as well. Finally, kinetic modeling of the accumulation of antibody variants is presented as a tool to determine the expected fraction of molecules that have undergone one or more degradation reactions.
Export Options
About this article
Cite this article as:
Vlasak J. and Ionescu R., Heterogeneity of Monoclonal Antibodies Revealed by Charge-Sensitive Methods, Current Pharmaceutical Biotechnology 2008; 9 (6) . https://dx.doi.org/10.2174/138920108786786402
DOI https://dx.doi.org/10.2174/138920108786786402 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Efficacy and Mechanism of Proteasome Inhibitors in Solid Tumor Treatment
Recent Patents on Anti-Cancer Drug Discovery Natural Bio-Drugs as Matrix Metalloproteinase Inhibitors: New Perspectives on the Horizon?
Recent Patents on Anti-Cancer Drug Discovery Growth Factor Signaling and Resistance to Cancer Chemotherapy
Current Topics in Medicinal Chemistry Chemistry and Health Effects of Bioactive Compounds in Selected Culinary Aromatic Herbs
Current Nutrition & Food Science Natural Product Inhibitors of the Ubiquitin-Proteasome Pathway
Current Drug Targets Polyphenols: Biological Activities, Molecular Targets, and the Effect of Methylation
Current Molecular Pharmacology Chronic Inflammation and Cancer: The Role of Endothelial Dysfunction and Vascular Inflammation
Current Pharmaceutical Design CXCR4 Receptor as a Promising Target for Oncolytic Drugs
Mini-Reviews in Medicinal Chemistry Use of N-acetyl-cysteine to Prevent Nephrotoxicity Associated with Iodinated Contrast Agents
Current Drug Therapy Deubiquitinating Enzyme Inhibitors and their Potential in Cancer Therapy
Current Cancer Drug Targets Ruxolitinib Regulates the Autophagy Machinery in Multiple Myeloma Cells
Anti-Cancer Agents in Medicinal Chemistry The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies
Anti-Cancer Agents in Medicinal Chemistry Sympathetic Signaling in Angiogenesis: Implications for Cancer Progression
Current Cancer Therapy Reviews Stem Cell Transplantation and MBL Replacement Therapy
Current Stem Cell Research & Therapy Recent Advances in Computer-Assisted Structure-Based Identification and Design of Histone Deacetylases Inhibitors
Current Topics in Medicinal Chemistry New Molecules and Strategies in the Field of Anticancer Agents
Current Medicinal Chemistry - Anti-Cancer Agents A Review on Novel Breast Cancer Therapies: Photodynamic Therapy and Plant Derived Agent Induced Cell Death Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Promising Targets in Anti-cancer Drug Development: Recent Updates
Current Medicinal Chemistry Recognition of Leishmania Parasites by Innate Immunity
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) The Dark Side of Stem Cells: Triggering Cancer Progression by Cell Fusion
Current Molecular Medicine