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Generation of Multivirus-specific T Cells to Prevent/treat Viral Infections after Allogeneic Hematopoietic Stem Cell Transplant
Published on: May 27, 2011
Adenovirus-mediated targeted gene therapy for breast cancer and for purging hematopoietic stem-cell sources
1Department of Human Genetics, Merck Research Laboratories, West Point, PA.
Abstract:
Gene therapy provides a potentially powerful approach for cancer treatment. One strategy is based on direct transfer of a suicide gene, which encodes enzymes that can activate a prodrug within tumor cells and thereby render the tumor cells sensitive to agents that are otherwise nontoxic to the cell. For example, introduction of the herpes simplex virus thymidine kinase gene (HSV-tk) or the bacterial cytosine deaminase (CD) gene, which respectively render mammalian cells sensitive to the otherwise nontoxic antiviral agent ganciclovir (1,2) and to the antifungal drug 5-fluorocytosine (3,4). Another novel prodrug activation system is the activation of conventional anticancer prodrug cyclo-phosphamide and ifosphamide by intratumor expression of mammalian cyto-chrome P450, such as rat 2B1 or human 2B6 to further sensitize cancer cells (5,6). Whereas gene therapy may provide a new therapeutic approach, clinical efficacy will require gene delivery systems, which possess both high gene-transduction efficiency and target-cell specificity.
Insights
Gene therapy offers a promising cancer treatment strategy using suicide genes to activate prodrugs, enhancing tumor cell sensitivity. Effective clinical use depends on efficient and specific gene delivery systems.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Gene therapy presents a novel strategy for cancer treatment.
- Suicide gene therapy involves transferring genes that activate prodrugs within tumor cells, increasing their sensitivity to non-toxic agents.
- Examples include herpes simplex virus thymidine kinase (HSV-tk) and bacterial cytosine deaminase (CD) genes.
Purpose of the Study:
- To explore the potential of gene therapy as a cancer treatment modality.
- To discuss prodrug activation systems utilizing suicide genes for enhanced cancer cell sensitization.
- To highlight the necessity of efficient and specific gene delivery systems for clinical efficacy.
Main Methods:
- Review of existing gene therapy strategies for cancer treatment.
- Discussion of suicide gene systems, including HSV-tk and CD gene therapy.
- Exploration of cytochrome P450-mediated prodrug activation systems.
Main Results:
- Suicide gene therapy can sensitize cancer cells to specific prodrugs like ganciclovir and 5-fluorocytosine.
- Mammalian cytochrome P450 enzymes can activate anticancer prodrugs like cyclophosphamide and ifosfamide.
- Gene therapy holds promise for cancer treatment by enabling targeted drug activation.
Conclusions:
- Gene therapy, particularly suicide gene therapy, offers a powerful approach to cancer treatment.
- Successful clinical application hinges on the development of gene delivery systems with high transduction efficiency and target-cell specificity.
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