Abstract
Protein therapeutics, such as antibodies, enzymes and toxins, are very promising reagents for the treatment of human disease. However, many therapeutic proteins are known to elicit immune responses when administered to humans. Certain antibodies work by neutralization; others reduce drug efficacy. It is clear that helper T cells are an important factor in the development of class-switched and affinity-maturated anti-therapeutic protein antibodies. Elimination of the T cell epitope seems reasonable, but it is probably impossible to remove all T cell epitopes from protein drugs because T cell epitopes are closely related to the major histocompatibility complex (MHC) molecules, which are known to be highly polymorphic. Accordingly, a possible practical approach for reducing immunogenicity involves the removal of B cell epitopes. In this case, reducing the affinity between the antigen and the B cell receptor may reduce B cell activation, even though the T cell will still be activated. Also a B cell epitope is not restricted by MHC class II molecules. This review seeks to address the identification and the characterization of B cell epitopes, and reports on the development of strategies for reducing immune response with modified B cell epitopes.
Keywords: Toxin, antibody, B cell epitope, ELISA, conformational epitope
Current Drug Targets
Title: Reducing the Immunogenicity of Protein Therapeutics
Volume: 10 Issue: 2
Author(s): Masanori Onda
Affiliation:
Keywords: Toxin, antibody, B cell epitope, ELISA, conformational epitope
Abstract: Protein therapeutics, such as antibodies, enzymes and toxins, are very promising reagents for the treatment of human disease. However, many therapeutic proteins are known to elicit immune responses when administered to humans. Certain antibodies work by neutralization; others reduce drug efficacy. It is clear that helper T cells are an important factor in the development of class-switched and affinity-maturated anti-therapeutic protein antibodies. Elimination of the T cell epitope seems reasonable, but it is probably impossible to remove all T cell epitopes from protein drugs because T cell epitopes are closely related to the major histocompatibility complex (MHC) molecules, which are known to be highly polymorphic. Accordingly, a possible practical approach for reducing immunogenicity involves the removal of B cell epitopes. In this case, reducing the affinity between the antigen and the B cell receptor may reduce B cell activation, even though the T cell will still be activated. Also a B cell epitope is not restricted by MHC class II molecules. This review seeks to address the identification and the characterization of B cell epitopes, and reports on the development of strategies for reducing immune response with modified B cell epitopes.
Export Options
About this article
Cite this article as:
Onda Masanori, Reducing the Immunogenicity of Protein Therapeutics, Current Drug Targets 2009; 10 (2) . https://dx.doi.org/10.2174/138945009787354511
DOI https://dx.doi.org/10.2174/138945009787354511 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
Call for Papers in Thematic Issues
New drug therapy for eye diseases
Eyesight is one of the most critical senses, accounting for over 80% of our perceptions. Our quality of life might be significantly affected by eye disease, including glaucoma, diabetic retinopathy, dry eye, etc. Although the development of microinvasive ocular surgery reduces surgical complications and improves overall outcomes, medication therapy is ...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
-
Critical Review of Malondialdehyde Analysis in Biological Samples
Current Pharmaceutical Analysis Tubulins as Therapeutic Targets in Cancer: from Bench to Bedside
Current Pharmaceutical Design Macrophage-Assisted Inflammation and Pharmacological Regulation of the Cholinergic Anti-Inflammatory Pathway
Current Medicinal Chemistry Immune Response Manipulation: Recombinant Immunoreceptors Endow T-Cells with Predefined Specificity
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Protein & Peptide Science Bugs and Drugs: Oncolytic Virotherapy in Combination with Chemotherapy
Current Pharmaceutical Biotechnology Some Developments Regarding Functional Food Products (Functional Foods)
Current Nutrition & Food Science Nano Drug Delivery in Treatment of Oral Cancer, A Review of the Literature
Current Drug Targets Extracellular Vesicles Isolated from Mesenchymal Stromal Cells Primed with Hypoxia: Novel Strategy in Regenerative Medicine
Current Stem Cell Research & Therapy The Pro-Survival Function of Akt Kinase can be Overridden or Altered to Contribute to Induction of Apoptosis
Current Cancer Drug Targets Methylation Profile of miR-9-1 and miR-9-1/-9-3 as Potential Biomarkers of Diabetic Retinopathy
Current Diabetes Reviews Host Genetic Factors and Treatment of Hepatitis C
Current Molecular Pharmacology Antimetastatic Activities and Mechanisms of Bisdioxopiperazine Compounds
Anti-Cancer Agents in Medicinal Chemistry Vascular Endothelial Growth Factor (VEGF) Signaling in Tumour Vascularization: Potential and Challenges
Current Vascular Pharmacology Zinc, Metallothioneins and Longevity: Interrelationships with Niacin and Selenium
Current Pharmaceutical Design Development of Nanomedicines and Nano-Similars: Recent Advances in Regulatory Landscape
Current Pharmaceutical Design Condition Optimization and Production of Extracellular l-Arginine Deiminase from Vibrio Alginolyticus 1374
Current Biotechnology The Sleeping Beauty Transposon Vector System for Treatment of Rare Genetic Diseases: An Unrealized Hope?
Current Gene Therapy Recent Developments on 1,2,4-Triazole Nucleus in Anticancer Compounds: A Review
Anti-Cancer Agents in Medicinal Chemistry Role of Imaging in Testicular Cancer
Current Medical Imaging