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Antitumor effect and cellular immunity activation by murine interferon-β gene transfer against intracerebral glioma in mouse

Gene Therapy volume 6, pages 1626–1633 (1999)Cite this article

Abstract

Cationic liposomes containing the human 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 evaluate antitumor effects fully, especially those related to activation of the host immune response. This article 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-β 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 a 16-fold reduction in the mean volume of residual gliomas in the brains of C57BL/6 mice and massive infiltration of cytotoxic T lymphocytes (CTL) within the residual tumor, while few CTL were infiltrated in controls including murine IFN-β, empty liposomes, naked plasmid expressing murine IFN-β, and liposomes containing β-galactosidase gene. In addition, 40% of mice treated with liposomes containing the murine IFN-β gene were completely cured. These findings indicated that activation of cellular immunity participates in antitumor effects in vivo together with direct effects of the IFN-β gene.

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Acknowledgements

We thank Mr Nobuaki Misawa and Ms Yoshie Ieda in the First Department of Pathology at the Nagoya University School of Medicine, Ms Miwako Nisizawa in the Department of Biochemistry at Aichi Cancer Center, and all participants in the Department of Clinical Pathology at the Kariya General Hospital for technical assistance.

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  1. Department of Neurosurgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    A Natsume, M Mizuno, Y Ryuke & J Yoshida

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  1. A Natsume
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  2. M Mizuno
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  3. Y Ryuke
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  4. J Yoshida
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Natsume, A., Mizuno, M., Ryuke, Y. et al. Antitumor effect and cellular immunity activation by murine interferon-β gene transfer against intracerebral glioma in mouse. Gene Ther 6, 1626–1633 (1999). https://doi.org/10.1038/sj.gt.3300990

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