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マウス脳内グリオーマモデルにおけるマウスβ型インターフェロン遺伝子による抗腫瘍効果と宿主腫瘍免疫の検討：夏目敦至、水野正明、立家康至、吉田　純（名大・脳外）

Antitumor effect and cellular immunity activation by murine interferon-β gene transfer against intracerebral glioma in mouse: Atsushi NATSUME, Masaaki MIZUNO, Yasushi RYUKE, Jun YOSHIDA (Dept. of Neurosurg., Nagoya Univ., Sch. of Med.)

We have developed novel approaches toward malignant glioma using cationic liposomes as an in vivo gene-transfer system. Cationic liposomes containing the interferon-β (IFN-β) gene induce marked growth inhibition in human glioma cells. In vivo experiments using an human glioma implanted into the brains of nude mice have demonstrated a definite growth-inhibitory effect, achieving complete tumor regression with multiple intratumoral injections of the gene. However, nude mouse studies are inadequate to fully evaluate antitumor effects, especially those related to activation of the host immune response. The present study aimed to investigate antitumor effects and immune response activation by murine IFN-β gene transfer in syngeneic mice. In vitro experiments demonstrated a stronger growth-inhibitory effect of liposomes containing the murine IFN-b gene on a GL261 mouse glioma cell line than exogenously added murine IFN-β. In in vivo experiments, intratumoral administration of liposomes containing the murine IFN-β gene resulted in an 18-fold reduction in the mean volume of residual gliomas in the brains of C57BL/6 mice and massive infiltration of cytotoxic T lymphocytes within the residual tumor. These findings indicated that activation of cellular immunity participates in antitumor effects in vivo together with direct effects of the IFN-β gene. Currently we have been determining whether the treatment-associated CTL we demonstrated have specific antitumor effect.