Antitumor Effect of an Adeno‐associated Virus Vector Containing the Human Interferon‐β Gene on Experimental Intracranial Human Glioma

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Abstract
We constructed an adeno‐associated virus (AAV) vector containing the human interferon‐β(HuIFN‐β) gene (AAV‐IFN‐β) and investigated its antitumor effect against human glioma cells (U251‐SP) inoculated into the brain of nude mice. Prior to this, we examined human glioma cells transduced with AAV‐IFN‐β using video‐enhanced contrast differential interference contrast (VEC‐DIC) microscopy. Infection of AAV‐IFN‐β induced apoptosis and secondary necrosis in human glioma cells. In in vivo experiments, we confirmed production of HuIFN‐β and induction of heat‐shock protein (HSP) in glioma cells transduced with AAV‐IFN‐β. Growth of the experimental gliomas was completely inhibited by six injections of AAV‐IFN‐β, starting 7 days after transplantation of glioma cells. In addition, the survival of mice treated with AAV‐IFN‐β was remarkably prolonged. These results indicate that AAV‐IFN‐β induces apoptosis of glioma cells and has a strong antitumor effect in this experimental glioma model.