Abstract
The prognosis of patients diagnosed with malignant gliomas including glioblastoma multiforme (GBM) is poor and there is an urgent need to develop and translate novel therapies into the clinic. Neural stem cells display remarkable tropism toward GBMs and thus may provide a platform to deliver oncolytic agents to improve survival. First we provide a brief review of clinical trials that have used intra-tumoral herpes simplex virus thymidine kinase (HSV/tk) gene therapy to treat brain tumors. Then, we review recent evidence that neural stem cells can be used to deliver HSV/tk to GBMs in animal models. While previous clinical trials used viruses or non-migratory vector-producing cells to deliver HSV/tk, the latter approaches were not effective in humans, primarily because of satellite tumor cells that escaped surgical resection and survived due to low efficiency delivery of HSV/tk. To enhance delivery of HSV/tk to kill gliomas cells, recent animal studies have focused on the ability of neural stem cells, transduced with HSV/tk, to migrate efficiently and selectively to regions occupied by GBM cells. This approach holds the promise of targeting GBM cells that have infiltrated the brain well beyond the original site of the tumor epicenter.
Keywords: Glioblastoma multiforme, tropism, neural stem cells, bystander effect, Herpes Simplex Virus / thymidine kinase
Current Stem Cell Research & Therapy
Title: Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas
Volume: 4 Issue: 1
Author(s): Prakash Rath, Huidong Shi, Joel A. Maruniak, N. Scott Litofsky, Bernard L. Maria and Mark D. Kirk
Affiliation:
Keywords: Glioblastoma multiforme, tropism, neural stem cells, bystander effect, Herpes Simplex Virus / thymidine kinase
Abstract: The prognosis of patients diagnosed with malignant gliomas including glioblastoma multiforme (GBM) is poor and there is an urgent need to develop and translate novel therapies into the clinic. Neural stem cells display remarkable tropism toward GBMs and thus may provide a platform to deliver oncolytic agents to improve survival. First we provide a brief review of clinical trials that have used intra-tumoral herpes simplex virus thymidine kinase (HSV/tk) gene therapy to treat brain tumors. Then, we review recent evidence that neural stem cells can be used to deliver HSV/tk to GBMs in animal models. While previous clinical trials used viruses or non-migratory vector-producing cells to deliver HSV/tk, the latter approaches were not effective in humans, primarily because of satellite tumor cells that escaped surgical resection and survived due to low efficiency delivery of HSV/tk. To enhance delivery of HSV/tk to kill gliomas cells, recent animal studies have focused on the ability of neural stem cells, transduced with HSV/tk, to migrate efficiently and selectively to regions occupied by GBM cells. This approach holds the promise of targeting GBM cells that have infiltrated the brain well beyond the original site of the tumor epicenter.
Export Options
About this article
Cite this article as:
Rath Prakash, Shi Huidong, Maruniak A. Joel, Litofsky Scott N., Maria L. Bernard and Kirk D. Mark, Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas, Current Stem Cell Research & Therapy 2009; 4 (1) . https://dx.doi.org/10.2174/157488809787169138
DOI https://dx.doi.org/10.2174/157488809787169138 |
Print ISSN 1574-888X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-3946 |
- 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
- Announcements
Related Articles
-
Novel Agents Aiming at Specific Molecular Targets Increase Chemosensitivity and Overcome Chemoresistance in Hematopoietic Malignancies
Current Pharmaceutical Design ADAM19/Adamalysin 19 Structure, Function, and Role as a Putative Target in Tumors and Inflammatory Diseases
Current Pharmaceutical Design In Vivo Cellular Imaging for Translational Medical Research
Current Medical Imaging Circulating microRNAs in Hepatocellular Carcinoma: Potential Diagnostic and Prognostic Biomarkers
Current Pharmaceutical Design Active Tumor Targeting of Nanomaterials Using Folic Acid, Transferrin and Integrin Receptors
Current Drug Discovery Technologies Pharmacological Approaches to Targeting Muscarinic Acetylcholine Receptors
Recent Patents on CNS Drug Discovery (Discontinued) Editorial [ The Role of Epidermal Growth Factor Receptor (EGFR) Targeting Drugs in the Treatment of Cancer Guest Editor: Fortunato Ciardiello ]
Current Cancer Therapy Reviews Thioureas as Building Blocks for the Generation of Heterocycles and Compounds with Pharmacological Activity: An Overview
Mini-Reviews in Organic Chemistry Host Pharmacogenetics in the Treatment of HIV and Cancer
Current Drug Safety Functional Genomics Approaches in Cancer Research
Current Genomics Meet Our Editorial Board Member
Current Cancer Therapy Reviews Pyrimidine Nucleosides in Molecular PET Imaging of Tumor Proliferation
Current Medicinal Chemistry Thalidomide–A Notorious Sedative to a Wonder Anticancer Drug
Current Medicinal Chemistry Colorectal Cancer Classification and Survival Analysis Based on an Integrated RNA and DNA Molecular Signature
Current Bioinformatics Cancer Therapy: Targeting Cell Cycle Regulators
Anti-Cancer Agents in Medicinal Chemistry The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations
Current Cancer Drug Targets Recent Developments in Targeting Breast Cancer Stem Cells
Recent Patents on Regenerative Medicine An Agathokakological Tale of Δ<sup>9</sup>-THC: Exploration of Possible Biological Targets
Current Drug Targets Gene Regulation in Cancer Gene Therapy Strategies
Current Medicinal Chemistry Neuroprotection by Estrogen and Progesterone in Traumatic Brain Injury and Spinal Cord Injury
Current Neuropharmacology