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Tomato thymidine kinase-based suicide gene therapy for malignant glioma-an alternative for Herpes Simplex virus-1 thymidine kinase.

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Author

  • H Stedt
  • H Samaranayake
  • J Kurkipuro
  • G Wirth
  • Louise Slot Christiansen
  • T Vuorio
  • A-M Määttä
  • Jure Piskur
  • S Ylä-Herttuala

Summary, in English

Malignant gliomas (MGs) are the most common malignant primary brain tumors with a short life estimate accompanied by a marked reduction in the quality of life. Herpes Simplex virus-1 thymidine kinase ganciclovir (HSV-TK/GCV) system is the best characterized enzyme prodrug therapy in use. However, lipophobicity of GCV and low enzymatic activity of HSV-TK reduce the treatment efficacy. Tomato TK (ToTK) has shown high activity in combination with its specific substrate azidothymidine (AZT). The aim of this study was to evaluate whether ToTK/AZT could be used as an alternative to HSV-TK/GCV therapy. Both treatments demonstrated cytotoxicity in human MG cells in vitro. In vivo, both treatments decreased tumor growth and tumors were smaller in comparison with controls in mouse orthotopic MG model. Survival of ToTK/AZT-treated mice was significantly increased compared with control mice (*P<0.05) but not as compared with HSV-TK/GCV-treated mice. No significant differences were observed in clinical chemistry safety analyses. We conclude that both treatments showed a beneficial treatment response in comparison to controls on tumor growth and ToTK/AZT also on survival. There were no significant differences between these treatments. Therefore ToTK/AZT could be considered as an alternative treatment option for MG because of its favorable therapeutic characteristics.Cancer Gene Therapy advance online publication, 23 January 2015; doi:10.1038/cgt.2014.76.

Publishing year

2015

Language

English

Pages

130-137

Publication/Series

Cancer Gene Therapy

Volume

22

Issue

3

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Biological Sciences

Status

Published

ISBN/ISSN/Other

  • ISSN: 1476-5500