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Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study

Gene Therapy volume 6, pages 1030–1037 (1999)Cite this article

Abstract

Contradictory experimental results and human trials have questioned the clinical relevance of the HSVtk/ganciclovir system. To bypass the problem of transfection efficiency, we used a glioma cell line stably expressing the HSVtk gene, which was also fully characterized from gene to protein. We also designed a more clinically relevant experimental protocol, consisting of late GCV delivery on large tumor formations. In short-term studies, histological examination revealed a significant decrease in tumor volume in GCV-treated animals from day 1 or from day 10 after cell inoculation. We observed that late GCV delivery is as efficient as early delivery, probably because GCV can reach tumor cells more easily when neoangiogenesis occurs. In long-term experiments, the survival of treated rats bearing 15-day tumors was improved by 60% compared with C6 control animals. Surprisingly, a 30% survival rate was observed in C6TK control animals. Nuclear magnetic resonance imaging demonstrated, in all surviving animals, a complete regression of tumors without mass effect. These results clearly demonstrate that the HSVtk/GCV system remains a potent therapeutic strategy, even when tested in large tumors, in contrast with the microscopic tumor formations previously reported.

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Acknowledgements

We would like to thank Dr J Janicot (Rhone-Poulenc Rorer Gencell) for the polyclonal rabbit-anti-HSV/TK serum and Dr R Barnoud for the Factor VIII immunological study. This work was supported by grants from the Centre d’application et Réseau de Thérapie Génique (Ministère de la Santé, Fondation pour la Recherche Médicale, Association Française de lutte contre les Myopathies, Ligue Contre le Cancer), ARC and Espoir.

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Authors and Affiliations

  1. Laboratoire de Neurobiologie Préclinique, INSERM U 318, Institut Féderatif de Recherche No. 1, CHU, Grenoble, France

    R Bouali-Benazzouz, M Lainé, J M Vicat, S Boisseau, F Thomas, M F Nissou, A L Benabid & F Berger

  2. Laboratoire de RMN Bioclinique, INSERM U 438, Institut Féderatif de Recherche No. 1, CHU, Grenoble, France

    C Rémy & N Fouilhé

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  1. R Bouali-Benazzouz
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Bouali-Benazzouz, R., Lainé, M., Vicat, J. et al. Therapeutic efficacy of the thymidine kinase/ganciclovir system on large experimental gliomas: a nuclear magnetic resonance imaging study. Gene Ther 6, 1030–1037 (1999). https://doi.org/10.1038/sj.gt.3300921

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