Address of Corresponding Author

Oncology 2005;69:503-508 (DOI: 10.1159/000091032)

  Key Words

• Herpes simplex virus thymidine kinase
• Ganciclovir
• Bystander effect
• Neural stem cell
• Suicide gene therapy

  Abstract

Objective: The herpes simplex virus thymidine kinase (HSVtk)/ganciclovir suicide gene therapy system has been considered as one of the most promising therapeutic strategies for malignant gliomas. We have been using HSVtk gene-transduced neural stem cells (NSCtk) that possess an ability to migrate toward a tumor mass for the treatment of experimental brain tumors. In the present study, we evaluated the potency of anti-tumor effect mediated by the bystander effect between NSCtk and C6 glioma cells in the HSVtk/ganciclovir suicide gene therapy system. Methods: NSCtk and C6 glioma cells were mixed at various ratios (NSCtk:C6 cell ratios of 1:1 to 1:64) and the bystander effect was evaluated both under in vitro and in vivo conditions. Results: In vitro co-culture experiment showed a complete tumor growth inhibition at the NSCtk:C6 ratios as low as 1:16. In vivo co-implantation study in the rat brain showed no visible tumors at the NSCtk:C6 ratios as low as 1:16 and all those rats survived more than 100 days. Conclusion: The results clearly demonstrated an extremely potent bystander effect between NSCtk and C6 cells, and the minimum number of NSCtk cells needed for the treatment of tumors was roughly estimated.

Copyright © 2005 S. Karger AG, Basel

  Author Contacts

Hiroki Namba, MD
Department of Neurosurgery, Hamamatsu University School of Medicine
1-20-1 Handayama
Hamamatsu, 431-3192 (Japan)
Tel. +81 53 435 2281, Fax +81 53 435 2282, E-Mail hnamba@hama-med.ac.jp

  Article Information

Received: June 21, 2005
Accepted after revision: October 15, 2005
Published online: January 16, 2006
Number of Print Pages : 6
Number of Figures : 3, Number of Tables : 0, Number of References : 17