Abstract
The potential of antibodies as “magic bullets” for cancer therapy has been appreciated for nearly a century. During the past 25 years, various scientific developments have made possible the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies (MoAbs). Intact, unconjugated MoAbs may: [1] produce anticancer effects through the immune system on the basis of interactions between the Fc portion of antibody and complement proteins and/or effector cells; [2] induce regulatory effects by neutralizing circulating ligands or blocking cell membrane receptors, thereby interfering with ligand/receptor interactions and signal transduction; [3] serve as immunogens for anti-cancer vaccines through the anti-idiotype-network cascade. Conjugated MoAbs can serve as carriers of other agents such as radioisotopes, natural toxins, chemotherapy drugs, cytokines, and immune cells. Important aspects of the antigenic target are the degree to which it is tumor-specific or tumor-associated, whether it internalizes or not, whether it is shed, the density of expression, and the physiologic significance of the antigen to the target cell. The clinical foundation for antibody-mediated therapy was laid in the 1980s when investigators established the safety of antibody administration, defined certain predictable antibody-mediated toxicities, and confirmed that antibodies could reach tumor targets and produce antitumor effects. A major limitation of these early mouse monoclonal antibodies was overcome with the production of antibodies with varying degrees of humanization. In 1997 rituximab (Rituxan®), a mouse-human chimeric anti-CD20, became the first MoAb approved by regulatory agencies for the treatment of a human malignancy.
Current Pharmaceutical Biotechnology
Title: The History and Rationale for Monoclonal Antibodies in the Treatment of Hematologic Malignancy
Volume: 2 Issue: 4
Author(s): R.O. Dillman
Affiliation:
Abstract: The potential of antibodies as “magic bullets” for cancer therapy has been appreciated for nearly a century. During the past 25 years, various scientific developments have made possible the production of unlimited quantities of clinical-grade murine, chimeric, and humanized monoclonal antibodies (MoAbs). Intact, unconjugated MoAbs may: [1] produce anticancer effects through the immune system on the basis of interactions between the Fc portion of antibody and complement proteins and/or effector cells; [2] induce regulatory effects by neutralizing circulating ligands or blocking cell membrane receptors, thereby interfering with ligand/receptor interactions and signal transduction; [3] serve as immunogens for anti-cancer vaccines through the anti-idiotype-network cascade. Conjugated MoAbs can serve as carriers of other agents such as radioisotopes, natural toxins, chemotherapy drugs, cytokines, and immune cells. Important aspects of the antigenic target are the degree to which it is tumor-specific or tumor-associated, whether it internalizes or not, whether it is shed, the density of expression, and the physiologic significance of the antigen to the target cell. The clinical foundation for antibody-mediated therapy was laid in the 1980s when investigators established the safety of antibody administration, defined certain predictable antibody-mediated toxicities, and confirmed that antibodies could reach tumor targets and produce antitumor effects. A major limitation of these early mouse monoclonal antibodies was overcome with the production of antibodies with varying degrees of humanization. In 1997 rituximab (Rituxan®), a mouse-human chimeric anti-CD20, became the first MoAb approved by regulatory agencies for the treatment of a human malignancy.
Export Options
About this article
Cite this article as:
R.O. Dillman , The History and Rationale for Monoclonal Antibodies in the Treatment of Hematologic Malignancy, Current Pharmaceutical Biotechnology 2001; 2 (4) . https://dx.doi.org/10.2174/1389201013378617
DOI https://dx.doi.org/10.2174/1389201013378617 |
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
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Novel Immunosuppressive Strategies for Bone Marrow Failure Syndromes: A Focus on Alemtuzumab
Mini-Reviews in Medicinal Chemistry Histone Deacetylase Inhibitors: An Attractive Strategy for Cancer Therapy
Current Medicinal Chemistry Functional and Clinical Significance of the Integrin Alpha Chain CD49d Expression in Chronic Lymphocytic Leukemia
Current Cancer Drug Targets MicroRNA Regulation of Programmed Cell Death Pathways in Cancer
Current Chemical Biology Natural Products as Exquisitely Potent Cytotoxic Payloads for Antibody- Drug Conjugates
Current Topics in Medicinal Chemistry Role of Nutrients and Phyto-compounds in the Modulation of Antimicrobial Resistance
Current Drug Metabolism Proteomic Analysis of Liver Preservation Solutions Prior to Liver Transplantation
Current Proteomics Gain-of-Function Mutations of Receptor Tyrosine Kinases in Gastrointestinal Stromal Tumors
Current Genomics Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design HIV-Related Lymphoproliferative Diseases in the Era of Combination Antiretroviral Therapy
Cardiovascular & Hematological Disorders-Drug Targets Advancement in Infection Control of Opportunistic Pathogen (Aspergillus spp.): Adjunctive Agents
Current Pharmaceutical Biotechnology Hypocholesterolemia
Current Vascular Pharmacology <sup>177</sup>Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay
Current Radiopharmaceuticals Disulfiram's Anticancer Activity: Evidence and Mechanisms
Anti-Cancer Agents in Medicinal Chemistry AKT-pathway Inhibition in Chronic Lymphocytic Leukemia Reveals Response Relationships Defined by TCL1
Current Cancer Drug Targets The Efficacy of Vitamin K, A Member Of Naphthoquinones in the Treatment of Cancer: A Systematic Review and Meta-Analysis
Current Cancer Drug Targets Platelet Function in Inflammatory Diseases: Insights from Clinical Studies
Inflammation & Allergy - Drug Targets (Discontinued) Immunotherapeutic Approaches in MS: Update on Pathophysiology and Emerging Agents or Strategies 2006
Endocrine, Metabolic & Immune Disorders - Drug Targets Novel and Emerging Drugs for Acute Myeloid Leukemia: Pharmacology and Therapeutic Activity
Current Medicinal Chemistry Exploiting Novel Cell Cycle Targets in the Development of Anticancer Agents
Current Cancer Drug Targets