Abstract
Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only in dividing cells and have shown potential for the treatment of malignant disease, including glioma. Phase I trials have demonstrated the safety of these viruses in various clinical settings but it is envisaged that for full efficacy they will be used in combination with other therapeutic modalities. To enhance virus-induced tumour cytotoxicity, we have engineered an ICP34.5 null mutant (HSV1716) of HSV1 which expresses the noradrenaline transporter gene (NAT). This virus is designated HSV1716/NAT. We have shown previously that introduction of the NAT gene into a range of tumour cells, via plasmid-mediated transfection, conferred the capacity for active uptake of the radiopharmaceutical [131I]MIBG and resulted in dosedependent toxicity. In this study, combination therapy utilising HSV1716/NAT and [131I]MIBG was assessed in vitro by the MTT assay. We demonstrate that the NAT gene, introduced by HSV1716/NAT into cultured glioma cells, was expressed 1 h after viral infection, enabling active uptake of [131I]MIBG. The combination of viral oncolysis and induced radiopharmaceutical uptake resulted in significantly enhanced cytotoxicity compared to either agent alone and the response was dose- and time-dependent. These studies show that the combination of oncolytic HSV therapy with targeted radiotherapy has the potential for effective tumour cell kill and warrants further investigation as a treatment for malignant glioma.
Keywords: hsv, glioma, gene therapy, targeted radiotherapy, oncolytic viral therapy
Medicinal Chemistry
Title: Assessment In Vitro of a Novel Therapeutic Strategy for Glioma, Combining Herpes Simplex Virus HSV1716-mediated Oncolysis with Gene Transfer and Targeted Radiotherapy
Volume: 1 Issue: 5
Author(s): M. Quigg, R. J. Mairs, S. M. Brown, J. Harland, P. Dunn, R. Rampling, A. Livingstone, L. Wilson and M. Boyd
Affiliation:
Keywords: hsv, glioma, gene therapy, targeted radiotherapy, oncolytic viral therapy
Abstract: Genetically engineered herpes simplex virus ICP34.5 null mutants replicate only in dividing cells and have shown potential for the treatment of malignant disease, including glioma. Phase I trials have demonstrated the safety of these viruses in various clinical settings but it is envisaged that for full efficacy they will be used in combination with other therapeutic modalities. To enhance virus-induced tumour cytotoxicity, we have engineered an ICP34.5 null mutant (HSV1716) of HSV1 which expresses the noradrenaline transporter gene (NAT). This virus is designated HSV1716/NAT. We have shown previously that introduction of the NAT gene into a range of tumour cells, via plasmid-mediated transfection, conferred the capacity for active uptake of the radiopharmaceutical [131I]MIBG and resulted in dosedependent toxicity. In this study, combination therapy utilising HSV1716/NAT and [131I]MIBG was assessed in vitro by the MTT assay. We demonstrate that the NAT gene, introduced by HSV1716/NAT into cultured glioma cells, was expressed 1 h after viral infection, enabling active uptake of [131I]MIBG. The combination of viral oncolysis and induced radiopharmaceutical uptake resulted in significantly enhanced cytotoxicity compared to either agent alone and the response was dose- and time-dependent. These studies show that the combination of oncolytic HSV therapy with targeted radiotherapy has the potential for effective tumour cell kill and warrants further investigation as a treatment for malignant glioma.
Export Options
About this article
Cite this article as:
Quigg M., Mairs J. R., Brown M. S., Harland J., Dunn P., Rampling R., Livingstone A., Wilson L. and Boyd M., Assessment In Vitro of a Novel Therapeutic Strategy for Glioma, Combining Herpes Simplex Virus HSV1716-mediated Oncolysis with Gene Transfer and Targeted Radiotherapy, Medicinal Chemistry 2005; 1 (5) . https://dx.doi.org/10.2174/1573406054864124
DOI https://dx.doi.org/10.2174/1573406054864124 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Drug-Loaded Nanocarriers in Tumor Targeted Drug Delivery
Current Biotechnology Functionalized Nanocarriers for Enhanced Bioactive Delivery to Squamous Cell Carcinomas: Targeting Approaches and Related Biopharmaceutical Aspects
Current Pharmaceutical Design Dendrimers as Novel Systems for Delivery of Neuropharmaceuticals to the Brain
CNS & Neurological Disorders - Drug Targets Effect of O6-Substituted Guanine Analogs on O6-methylguanine DNA-methyltransferase Expression and Glioblastoma Cells Viability
Medicinal Chemistry microRNA as Biomarkers and Regulator of Cardiovascular Development and Disease
Current Pharmaceutical Design Nanoparticles in Melanoma
Current Medicinal Chemistry Impaired Expression and Function of Cancer-Related Enzymes by Anthocyans: An Update
Current Enzyme Inhibition Patent Selections
Recent Patents on Biotechnology Pentacyclic Triterpenoids and Their Saponins with Apoptosis-Inducing Activity
Current Topics in Medicinal Chemistry NGR-based Strategies for Targeting Delivery of Chemotherapeutics to Tumor Vasculature
Anti-Cancer Agents in Medicinal Chemistry Design of New Improved Curcumin Derivatives to Multi-targets of Cancer and Inflammation
Current Drug Targets Inducers of Heme Oxygenase-1
Current Pharmaceutical Design Tumor Protein p63/microRNA Network in Epithelial Cancer Cells
Current Genomics Recent Progress in the Development of ATP-Competitive and Allosteric Akt Kinase Inhibitors
Current Topics in Medicinal Chemistry Inhibition of Glycolysis and Glutaminolysis: An Emerging Drug Discovery Approach to Combat Cancer
Current Topics in Medicinal Chemistry Lactate Transporters and pH Regulation: Potential Therapeutic Targets in Glioblastomas
Current Cancer Drug Targets Interaction and Structural Modification of Topoisomerase IIα by Peptidyl Prolyl Isomerase, pin1: An In Silico Study
Protein & Peptide Letters Purinergic Receptors and Pain
Current Pharmaceutical Design Suicide Gene Therapy Mediated by the Herpes Simplex Virus Thymidine Kinase Gene / Ganciclovir System: Fifteen Years of Application
Current Gene Therapy VEGF in Tumor Progression and Targeted Therapy
Current Cancer Drug Targets