Abstract
With the introduction of sophisticated tools of molecular biology, prodrug activating gene therapies have evolved as a novel therapeutic option for high-grade malignant gliomas. Herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) is an extensively studied form of cytotoxic gene therapies. It is especially applicable for localized cancers, such as malignant glioma because of its restricted anatomical location and absence of metastasis. The early successes in the treatment of experimental malignant gliomas in the 1990s, gave impetus to further test this approach in this devastating disease. In malignant glioma, the recurrence after conventional therapy is inevitable, due to the residual cells in the tumor bed. The fascinating feature of adenoviral HSV-tk is that it attacks the residual dividing tumor cells without affecting the non-dividing neurons and furthermore, exploits them to destroy the malignant cells via so-called bystander- effect. Clinical Phase I and II studies have shown significant survival advantage and excellent safety profile when compared to conventional treatments. Thus, the adenoviral mediated HSV-tk gene therapy is a promising new adjuvant treatment for patients with operable high-grade glioma.
Keywords: Glioma, adenoviral vector, herpes simplex virus 1 -thymidine kinase, ganciclovir, gene therapy, bystander-effect
Current Gene Therapy
Title: Adenovirus Mediated Herpes Simplex Virus-Thymidine Kinase/Ganciclovir Gene Therapy for Resectable Malignant Glioma
Volume: 9 Issue: 5
Author(s): Ann-Marie Maatta, Haritha Samaranayake, Jere Pikkarainen, Thomas Wirth and Seppo Yla-Herttuala
Affiliation:
Keywords: Glioma, adenoviral vector, herpes simplex virus 1 -thymidine kinase, ganciclovir, gene therapy, bystander-effect
Abstract: With the introduction of sophisticated tools of molecular biology, prodrug activating gene therapies have evolved as a novel therapeutic option for high-grade malignant gliomas. Herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) is an extensively studied form of cytotoxic gene therapies. It is especially applicable for localized cancers, such as malignant glioma because of its restricted anatomical location and absence of metastasis. The early successes in the treatment of experimental malignant gliomas in the 1990s, gave impetus to further test this approach in this devastating disease. In malignant glioma, the recurrence after conventional therapy is inevitable, due to the residual cells in the tumor bed. The fascinating feature of adenoviral HSV-tk is that it attacks the residual dividing tumor cells without affecting the non-dividing neurons and furthermore, exploits them to destroy the malignant cells via so-called bystander- effect. Clinical Phase I and II studies have shown significant survival advantage and excellent safety profile when compared to conventional treatments. Thus, the adenoviral mediated HSV-tk gene therapy is a promising new adjuvant treatment for patients with operable high-grade glioma.
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Maatta Ann-Marie, Samaranayake Haritha, Pikkarainen Jere, Wirth Thomas and Yla-Herttuala Seppo, Adenovirus Mediated Herpes Simplex Virus-Thymidine Kinase/Ganciclovir Gene Therapy for Resectable Malignant Glioma, Current Gene Therapy 2009; 9 (5) . https://dx.doi.org/10.2174/156652309789753365
DOI https://dx.doi.org/10.2174/156652309789753365 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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