Selective killing of glioma cell lines using an astrocyte-specific expression of the herpes simplex virus-thymidine kinase gene

Gene therapy using the herpes simplex virus thymidine kinase gene (HSV-TK) is a promising new approach for the treatment of gliomas, a tumor type with a poor prognosis. To limit the toxic effects of this procedure, it is desirable to restrict expression of the HSV-TK gene to the target cells. This c...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1998-10, Vol.58 (20), p.4577-4580
Main Authors: VANDIER, D, RIXE, O, BRENNER, M, GOUYETTE, A, BESNARD, F
Format: Article
Language:English
Subjects:
Antineoplastic agents
Astrocytes - metabolism
Biological and medical sciences
Chemotherapy
Ganciclovir - pharmacology
Genetic Therapy
Glial Fibrillary Acidic Protein - analysis
Glial Fibrillary Acidic Protein - genetics
Glioma - pathology
Glioma - therapy
Humans
Medical sciences
Pharmacology. Drug treatments
Promoter Regions, Genetic
Simplexvirus - enzymology
Thymidine Kinase - genetics
Tumor Cells, Cultured
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Summary:Gene therapy using the herpes simplex virus thymidine kinase gene (HSV-TK) is a promising new approach for the treatment of gliomas, a tumor type with a poor prognosis. To limit the toxic effects of this procedure, it is desirable to restrict expression of the HSV-TK gene to the target cells. This can be accomplished by use of the promoter of the glial fibrillary acidic protein gene, an intermediate filament protein expressed primarily in astrocytes. A plasmid containing the HSV-TK gene, driven by the human glial fibrillary acidic protein promoter gfa2, was lipofected into glioma cell lines and into an ovarian cancer cell line. Treatment with ganciclovir showed efficient killing of glioma cells, with no effect on the ovarian cells. Thus, the gfa2 promoter is a promising candidate for directing expression of toxic genes to gliomas.
ISSN:0008-5472
1538-7445