Potent bystander effect in suicide gene therapy using neural stem cells transduced with herpes simplex virus thymidine kinase gene.

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.