Abstract
Primary brain tumors including anaplastic astrocytomas and glioblastoma multiforme are difficult to treat because of their locally invasive nature and chemoradioresistance. Novel therapies are needed. One class of therapeutics is fusion proteins consisting of peptide toxins fused to brain tumor selective ligands. DAB389EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). DAB389EGF is selectively toxic to EGF receptor (EGFR) overexpressing cells. Close to half of all high-grade primary brain tumors have EGFR gene amplification and EGFR overexpression. With the use of convection-enhanced delivery (CED), DAB389EGF may be delivered locally at high concentrations to the brain tumor. CED would avoid many of the pharmacologic and toxicologic barriers which have limited effective use of this agent including rapid clearance from the circulation, high anti-diphtheria toxin antibody titers in the blood and toxicities to the liver and kidney. Both cell lines and animal models are available to assess the potential of this agent for brain tumor therapy. Since significant amounts of clinical grade DAB389EGF are available, some careful additional preclinical efficacy work should lead to testing of this agent in patients within the next few years.
Keywords: dab389egf, epidermal growth factor, refractory glioblastoma multiforme, fusion protein, astrocytomas multiforme
Current Pharmaceutical Biotechnology
Title: DAB389EGF Fusion Protein Therapy of Refractory Glioblastoma Multiforme
Volume: 4 Issue: 1
Author(s): Kimberley A. Cohen, TieFu Liu, Reid Bissonette, Raj K. Puri and Arthur E. Frankel
Affiliation:
Keywords: dab389egf, epidermal growth factor, refractory glioblastoma multiforme, fusion protein, astrocytomas multiforme
Abstract: Primary brain tumors including anaplastic astrocytomas and glioblastoma multiforme are difficult to treat because of their locally invasive nature and chemoradioresistance. Novel therapies are needed. One class of therapeutics is fusion proteins consisting of peptide toxins fused to brain tumor selective ligands. DAB389EGF is a fusion protein composed of the catalytic and translocation domains of diphtheria toxin fused via a His-Ala linker to human epidermal growth factor (EGF). DAB389EGF is selectively toxic to EGF receptor (EGFR) overexpressing cells. Close to half of all high-grade primary brain tumors have EGFR gene amplification and EGFR overexpression. With the use of convection-enhanced delivery (CED), DAB389EGF may be delivered locally at high concentrations to the brain tumor. CED would avoid many of the pharmacologic and toxicologic barriers which have limited effective use of this agent including rapid clearance from the circulation, high anti-diphtheria toxin antibody titers in the blood and toxicities to the liver and kidney. Both cell lines and animal models are available to assess the potential of this agent for brain tumor therapy. Since significant amounts of clinical grade DAB389EGF are available, some careful additional preclinical efficacy work should lead to testing of this agent in patients within the next few years.
Export Options
About this article
Cite this article as:
Cohen A. Kimberley, Liu TieFu, Bissonette Reid, Puri K. Raj and Frankel E. Arthur, DAB389EGF Fusion Protein Therapy of Refractory Glioblastoma Multiforme, Current Pharmaceutical Biotechnology 2003; 4 (1) . https://dx.doi.org/10.2174/1389201033378039
DOI https://dx.doi.org/10.2174/1389201033378039 |
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
- 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
-
Preclinical Evidence on the Anticancer Properties of Food Peptides
Protein & Peptide Letters Patent Selections:
Recent Patents on CNS Drug Discovery (Discontinued) A Potencial Theranostic Agent for EGF-R Expression Tumors: 177Lu- DOTA-Nimotuzumab
Current Radiopharmaceuticals Chemotherapy and Delivery in the Treatment of Primary Brain Tumors
Current Clinical Pharmacology Purine Analogues as Kinase Inhibitors: A Review
Recent Patents on Anti-Cancer Drug Discovery Challenges and Strategies in Precision Medicine for Non-Small-Cell Lung Cancer
Current Pharmaceutical Design The Development of Epigenetics and Related Inhibitors for Targeted Drug Design in Cancer Therapy
Current Topics in Medicinal Chemistry Selenium Compounds and Apoptotic Modulation: A New Perspective in Cancer Therapy
Mini-Reviews in Medicinal Chemistry G-Quadruplex Interacting Agents Targeting the Telomeric G-Overhang Are More than Simple Telomerase Inhibitors
Current Medicinal Chemistry - Anti-Cancer Agents Functional Evaluation of Imatinib mesylate in Hepatocellular Carcinoma Cells
Recent Patents on Biomarkers Flavonoids as Anticancer Agents: Recent Progress and State of the Art?
Current Organic Chemistry Inventions Designed to Enhance Drug Delivery Across Epithelial and Endothelial Cells Through the Paracellular Pathway
Recent Patents on Drug Delivery & Formulation Stressed to Death: Targeting Endoplasmic Reticulum Stress Response Induced Apoptosis in Gliomas
Current Pharmaceutical Design A Rational Approach to Target the Epidermal Growth Factor Receptor in Glioblastoma
Current Cancer Drug Targets Pharmacological Approaches to Targeting Muscarinic Acetylcholine Receptors
Recent Patents on CNS Drug Discovery (Discontinued) Id-1B, an Alternatively Spliced Isoform of the Inhibitor of Differentiation-1, Impairs Cancer Cell Malignancy Through Inhibition of Proliferation and Angiogenesis
Current Molecular Medicine Exosomes and Lung Cancer: Roles in Pathophysiology, Diagnosis and Therapeutic Applications
Current Medicinal Chemistry Anti-Cancer Effects of a New Docosahexaenoic Acid Monoacylglyceride in Lung Adenocarcinoma
Recent Patents on Anti-Cancer Drug Discovery Redox Environment and its Meaning for Breast Cancer Cells Fate
Current Cancer Drug Targets Snake Venom L-Amino Acid Oxidases: Some Consideration About their Functional Characterization
Protein & Peptide Letters