Abstract
Graft versus host disease (GVHD) is a T cell mediated phenomenon that arises following allogeneic haematopoietic stem cell transplantation, and may be particularly severe in the context of human leukocyte antigen (HLA) mismatched procedures. Although GVHD can be largely abrogated through T cell depletion, such measures result in loss of graft potency and reduced anti-viral and anti-leukaemic effects. The genetic modification of T cells to carry a suicide gene mechanism has been advocated as means of allowing T cells to be harnessed for their beneficial effects, and safely eliminated in the event of significant GVHD. The feasibility of the strategy has been demonstrated in clinical studies using T cells modified by retroviral transduction to encode the herpes simplex thymidine kinase (HSVTK) gene to treat patients with haematological malignancies. However, a number of limitations associated with current protocols have become apparent. Most notably, the process of retroviral transduction, which requires pre-activation of T cells, appears to impair subsequent functional potential. Efforts are now directed towards circumventing the pre-activation requirements of retroviral vectors by using alternative lentiviral systems, in association with improved suicide gene / prodrug combinations.
Keywords: suicide gene, graft versus host disease, retroviral vectors, stem cell transplantation
Current Gene Therapy
Title: T Cell Suicide Gene Therapy to Aid Haematopoietic Stem Cell Transplantation
Volume: 5 Issue: 1
Author(s): W. Qasim, H. B. Gaspar and A. J. Thrasher
Affiliation:
Keywords: suicide gene, graft versus host disease, retroviral vectors, stem cell transplantation
Abstract: Graft versus host disease (GVHD) is a T cell mediated phenomenon that arises following allogeneic haematopoietic stem cell transplantation, and may be particularly severe in the context of human leukocyte antigen (HLA) mismatched procedures. Although GVHD can be largely abrogated through T cell depletion, such measures result in loss of graft potency and reduced anti-viral and anti-leukaemic effects. The genetic modification of T cells to carry a suicide gene mechanism has been advocated as means of allowing T cells to be harnessed for their beneficial effects, and safely eliminated in the event of significant GVHD. The feasibility of the strategy has been demonstrated in clinical studies using T cells modified by retroviral transduction to encode the herpes simplex thymidine kinase (HSVTK) gene to treat patients with haematological malignancies. However, a number of limitations associated with current protocols have become apparent. Most notably, the process of retroviral transduction, which requires pre-activation of T cells, appears to impair subsequent functional potential. Efforts are now directed towards circumventing the pre-activation requirements of retroviral vectors by using alternative lentiviral systems, in association with improved suicide gene / prodrug combinations.
Export Options
About this article
Cite this article as:
Qasim W., Gaspar B. H. and Thrasher J. A., T Cell Suicide Gene Therapy to Aid Haematopoietic Stem Cell Transplantation, Current Gene Therapy 2005; 5 (1) . https://dx.doi.org/10.2174/1566523052997497
DOI https://dx.doi.org/10.2174/1566523052997497 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- 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
-
Scorpion Toxin Polyptides as Therapeutic Agents: An Overview
Protein & Peptide Letters The Use of SIFT-MS to Investigate Headspace Aldehydes as Markers of Lipid Peroxidation
Current Analytical Chemistry Editorial [Hot Topic: Designing New Drugs For High Grade Gliomas (Executive Guest Editor: Guido Frosina)]
Current Pharmaceutical Design Deciphering the Systems Biology of mTOR Inhibition by Integrative Transcriptome Analysis
Current Pharmaceutical Design Methods to Assess Tissue-Specific Distribution and Metabolism of Drugs
Current Drug Metabolism Cancer Vaccines: Emphasis on Pediatric Cancers
Current Pharmaceutical Design The Role of Natural Products in the Discovery of New Drug Candidates for the Treatment of Neurodegenerative Disorders I: Parkinsons Disease
CNS & Neurological Disorders - Drug Targets TRAIL-Based Therapeutic Approaches for the Treatment of Pediatric Malignancies
Current Medicinal Chemistry Inhibition of Angiogenesis as a Treatment Strategy for Neuroblastoma
Current Cancer Therapy Reviews Use of E. coli Purine Nucleoside Phosphorylase in the Treatment of Solid Tumors
Current Pharmaceutical Design The Interactions of the 5-HT3 Receptor with Quipazine-Like Arylpiperazine Ligands. The Journey Track at the End of the First Decade of the Third Millennium
Current Topics in Medicinal Chemistry Studies on Target Genes of General Anesthetics-Version 2
Medicinal Chemistry Reviews - Online (Discontinued) Recent Advances in Use of Topoisomerase Inhibitors in Combination Cancer Therapy
Current Topics in Medicinal Chemistry Neuropilin-1 (NRP-1) and Magnetic Nanoparticles, a Potential Combination for Diagnosis and Therapy of Gliomas
Current Pharmaceutical Design Role of Gap Junction Channel in the Development of Beat-to-Beat Action Potential Repolarization Variability and Arrhythmias
Current Pharmaceutical Design CD133+ Glioblastoma Stem-Like Cells Induce Vascular Mimicry in Vivo
Current Neurovascular Research Role of EGFR Inhibitors in the Treatment of Central Nervous System Metastases from Non-Small Cell Lung Cancer
Current Cancer Drug Targets Tumour Gene Therapy Monitoring Using Magnetic Resonance Imaging and Spectroscopy
Current Gene Therapy Antigenic Differences Between Normal and Malignant Cells as a Basis for Treatment of Intracerebral Neoplasms Using a DNA-Based Vaccine
Current Genomics Single-Photon Emission Computed Tomography Tracers for Predicting and Monitoring Cancer Therapy
Current Pharmaceutical Biotechnology