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 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
Latest Advancements in Biotherapeutics
The scope of this thematic issue is to comprehensively explore the rapidly evolving landscape of biotherapeutics, emphasizing breakthroughs in precision medicine. Encompassing diverse therapeutic modalities, the issue will delve into the latest developments in monoclonal antibodies, CRISPR/Cas gene editing, CAR-T cell therapies, and innovative drug delivery systems, such as nanoparticle-based ...read more
- 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
-
Discovery of Structurally Diverse Nonsteroidal SPRMs Based on a Screening Hit, 1,2-Dihydro-2,2,4-Trimethyl-6-Phenylquinolinone
Current Topics in Medicinal Chemistry A New Series of Antileukemic Agents: Design, Synthesis, <i>In Vitro</i> and <i>In Silico</i> Evaluation of Thiazole-Based ABL1 Kinase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Anticancer Effect of a Curcumin Derivative B63: ROS Production and Mitochondrial Dysfunction
Current Cancer Drug Targets Microenvironmental Interactions in Chronic Lymphocytic Leukemia: Hints for Pathogenesis and Identification of Targets for Rational Therapy
Current Pharmaceutical Design Viral Origins of Human Cancer
Current Medicinal Chemistry A Structural Insight into Hydroxamic Acid Based Histone Deacetylase Inhibitors for the Presence of Anticancer Activity
Current Medicinal Chemistry Novel Chiral LC Methods for the Enantiomeric Separation of Bicalutamide and Thalidomide on Amylose Based Immobilized CSP
Current Pharmaceutical Analysis Should the Status of the Pathway Mediated by BRCA1 and BRCA2 be Evaluated Before Selecting Cancer Chemotherapy Drugs?
Current Pharmacogenomics Perspectives in Engineered Mesenchymal Stem/Stromal Cells Based Anti- Cancer Drug Delivery Systems
Recent Patents on Anti-Cancer Drug Discovery Structure-Activity Relationship Analyses of Glycyrrhetinic Acid Derivatives as Anticancer Agents
Mini-Reviews in Medicinal Chemistry The Ubiquitin Proteasome System as a Potential Target for the Treatment of Neurodegenerative Diseases
Current Pharmaceutical Design Preferentially Expressed Antigen in Melanoma (PRAME) and the PRAME Family of Leucine-Rich Repeat Proteins
Current Cancer Drug Targets Molecular Targeted Agents Combined with Chemo-Radiation in the Treatment of Locally Advanced Cervix Cancer
Reviews on Recent Clinical Trials Inhibition of Polo-Like Kinase 1 by BI2536 Reverses the Multidrug Resistance of Human Hepatoma Cells In Vitro and In Vivo
Anti-Cancer Agents in Medicinal Chemistry Signaling Pathways Responsible for Cancer Cell Invasion as Targets for Cancer Therapy
Current Cancer Drug Targets The Medicinal Chemistry of Peptides
Current Medicinal Chemistry Metalloprotein Inhibitors for the Treatment of Human Diseases
Current Topics in Medicinal Chemistry MicroRNAs in Lymphoma: Regulatory Role and Biomarker Potential
Current Genomics Second Generation Proteasome Inhibitors in Multiple Myeloma
Anti-Cancer Agents in Medicinal Chemistry Synthetic 2-Methoxyestradiol Derivatives: Structure-Activity Relationships
Current Medicinal Chemistry