Local tumour irradiation enhances the anti-tumour effect of a double-suicide gene therapy system in a murine glioma model

Szilvia Desaknai, Katalin Lumniczky, Olga Esik, Hirofumi Hamada, Geza Safrany

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background: Gliomas are invasive malignant tumours with poor prognosis. Combination of gene directed enzyme pro-drug therapy with existing treatment modalities might open new therapeutic potentials. Methods: Murine glioma 261 (G1261) cells were transduced with an adenoviral vector (Adex-CAUPTK) encoding both uracil phosphoribosyltransferase and thymidine kinase genes which sensitise cells to 5-fluorouracil (5-FU) and ganciclovir (GC), respectively. Subcutaneous or intracranial tumours were established in C57Bl mice by transplanting drug-sensitising gene containing G1261 cells. In vitro growing cells or established tumours were treated with 5-FU, GC and ionising radiation either alone or in combinations. Finally, subcutaneous tumours were established with non-transduced cells, directly injected with Adex-CAUPTK, and mice were treated with combinations of 5-FU, GC and tumour irradiation. Results: In vitro treatment of transduced G1261 cells with both 5-FU and GC showed enhanced cytotoxic effect compared with single agents. Combination of drug treatments with irradiation greatly increased cytotoxicity. In subcutaneous and intracranial tumours double-agent treatment was more effective than a single drug. Combination with local irradiation highly improved the anti-tumour effect (90-100% survival) even when only part of the tumour cells carried drug-sensitising genes (40-50% survival at 10% rate). Treatment of established tumours with direct intra-tumour Adex-CAUPTK inoculations and intraperitoneal 5-FU, GC injections slowed down tumour progression that was further enhanced by local irradiation. Conclusion: The combination of double-suicide gene therapy with local irradiation is a promising tool to eradicate small, residual tumours.

Original languageEnglish
Pages (from-to)377-385
Number of pages9
JournalJournal of Gene Medicine
Volume5
Issue number5
DOIs
Publication statusPublished - May 1 2003

Keywords

  • 5-fluorouracil
  • GDEPT
  • Ganciclovir
  • Glioma
  • Irradiation

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery
  • Genetics(clinical)

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