Gene therapy of rat C6 glioma using adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene: long-term follow-up by magnetic resonance imaging

The herpes simplex virus thymidine kinase gene was transferred into C6 glioma cells by infection with a recombinant adenovirus. In vitro, a 10 microM ganciclovir concentration was able to kill 100% of the infected cells. For in vivo experiments, brain tumors were established by stereotactic injectio...

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Published inGene therapy Vol. 3; no. 4; p. 315
Main Authors Maron, A, Gustin, T, Le Roux, A, Mottet, I, Dedieu, J F, Brion, J P, Demeure, R, Perricaudet, M, Octave, J N
Format Journal Article
LanguageEnglish
Published England 01.04.1996
Subjects
Adenoviridae - genetics
Animals
Brain Neoplasms - genetics
Brain Neoplasms - pathology
Brain Neoplasms - therapy
Ganciclovir - therapeutic use
Gene Transfer Techniques
Genes, Viral
Genetic Therapy - methods
Genetic Vectors
Glioma - genetics
Glioma - pathology
Glioma - therapy
Magnetic Resonance Imaging
Male
Rats
Rats, Wistar
Simplexvirus - genetics
Thymidine Kinase - genetics
Time Factors
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Summary:The herpes simplex virus thymidine kinase gene was transferred into C6 glioma cells by infection with a recombinant adenovirus. In vitro, a 10 microM ganciclovir concentration was able to kill 100% of the infected cells. For in vivo experiments, brain tumors were established by stereotactic injection of C6 glioma cells in the caudate nucleus of rats. Five days later, the recombinant adenovirus was inoculated into the tumors and the animals were treated by intraperitoneal injections of ganciclovir for 14 days. At the end of ganciclovir therapy, histological examination revealed a 28-fold decrease in tumor volumes in the treated animals, as compared with control animals. In long-term studies, the mean survival time of the treated animals were four-fold longer than that of control ones. Magnetic resonance imaging demonstrated an apparent complete tumor regression in 62% of the animals. However, late tumor recurrence was observed in the treated animals. Repeated inoculation of C6 glioma cells in the contralateral hemisphere of long-term surviving animals resulted in either tumor rejection or slowly growing tumors. These findings demonstrate the potential efficacy of adenovirus-mediated transfer of the herpes simplex virus thymidine kinase gene and ganciclovir administration in the treatment of rat gliomas.
ISSN:0969-7128