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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Yoshida J, Kobayashi T, Kageyama N . Multimodality treatment of malignant glioma: effect of chemotherapy with ACNU and immunotherapy with N-CWS Neurol Med Chir 1984 24: 19–26
Muller H, Brock M, Ernest H . Long-term survival and recurrence-free interval in combined surgical, radio- and chemotherapy of malignant brain gliomas Clin Neurol Neurosurg 1985 87: 167–171
Ram Z et al. Therapy of malignant brain tumors by intratumoral implantation of retroviral vector-producing cells Nature Med 1997 3: 1354–1361
Lundblad D, Lundgren E . Block of a glioma cell line in S by interferon Int J Cancer 1981 27: 749–754
Cook AW, Carter WA, Nidzgorski F, Akhtar L . Human brain tumor-derived cell lines: growth rate reduced by human fibroblast interferon Science 1983 219: 881–883
Yoshida J et al. Antitumor activity of interferon-β against malignant glioma in combination with chemotherapeutic agent of nitrosourea (ACNU) In: Cantell K, Schellekens H (eds) The Biology of the Interferon System Martinus Nijhoff: Boston 1986 pp 399–406
Yoshida J, Kajita Y, Wakabayashi T, Sugita K . Long-term follow-up results of 175 patients with malignant glioma: importance of radical tumour resection and postoperative adjuvant therapy with interferon, ACNU and radiation Acta Neurochir 1994 127: 55–59
Wells V, Mallucci L . Cell cycle regulation (G1) by autocrine interferon and dissociation between autocrine interferon and 2′, 5′-oligoadenylate synthetase expression J Interferon Res 1988 8: 793–802
Larsson I et al. Interferon production in glia and glioma cell lines Infect Immun 1978 22: 786–789
James D et al. Chromosome 9 deletion mapping reveals interferon α and interferon β-1 gene deletions in human glial tumors Cancer Res 1991 51: 1684–1688
Mizuno M et al. Growth inhibition of glioma cells transfected with the human β-interferon gene by liposomes coupled with a monoclonal antibody Cancer Res 1990 50: 7826–7829
Mizuno M, Yoshida J, Sugita K, Yagi K . Growth inhibition of glioma cells of different cell lines by human interferon-β produced in the cells transfected with its gene by means of liposomes J Clin Biochem Nutr 1990 9: 73–77
Yagi K et al. Interferon-β endogenously produced by intratumoral injection of cationic liposome-encapsulated gene: cytocidal effect on glioma transplanted into nude mouse brain Biochem Mol Biol Int 1994 32: 167–171
Yoshida J, Mizuno M, Yagi K . Antitumor effect of endogenous human β-interferon on malignant glioma and augmentation of the effect by tumor necrosis facter-α J Clin Biochem Nutr 1992 12: 153–160
Yoshida J, Mizuno M, Yagi K . Secretion of human β-interferon into the cystic fluid of glioma transfected with the interferon gene J Clin Biochem Nutr 1991 11: 123–128
Mizuno M, Yoshida J . Effect of human interferon-β gene transfer upon human glioma, transplanted into nude mouse brain, involves induced natural killer cells Cancer Immunol Immunother 1998 47: 227–232
Mori T et al. A consideration on pharmacokinetics of a new water-soluble anti-tumor nitrosourea, ACNU, in patients with malignant brain tumor Brain Nerve 1979 31: 601–606
Takakura K et al. Effect of ACNU and radiotherapy on a malignant glioma J Neurosurg 1986 64: 53–57
Yoshida J, Mizuno M, Yagi K . Cytotoxity of human β-interferon produced in human glioma cells transfected with its gene by means of liposomes Biochem Int 1992 28: 1055–1061
von Hoegen P . Synergistic role of type I interferons in the induction of protective cytotoxic T lymphocytes Immun Lett 1995 47: 157–162
Chamberlain RS et al. Costimulation enhances the active immunotherapy effect of recombinant anticancer vaccines Cancer Res 1996 56: 2832–2836
Kuroki M et al. Antitumor effect of recombinant murine interferon-beta against mouse malignant glioma J Interferon Res 1987 7: 301–311
Watanabe Y, Kawade Y . Induction, production and purification of natural mouse IFN-α and -β In: Clemens MJ, Morris AG, Gearing AJH (eds) Lymphokines and Interferons: A Practical Approach IRL: Oxford 1987 pp 1–14
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.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gt.3300990
Keywords
This article is cited by
-
Interferon-beta inhibits human glioma stem cell growth by modulating immune response and cell cycle related signaling pathways
Cell Regeneration (2022)
-
Liposomal formulations of carboplatin injected by convection-enhanced delivery increases the median survival time of F98 glioma bearing rats
Journal of Nanobiotechnology (2018)
-
Interferon-β gene-modified human bone marrow mesenchymal stem cells attenuate hepatocellular carcinoma through inhibiting AKT/FOXO3a pathway
British Journal of Cancer (2013)
-
Curative one-shot systemic virotherapy in murine myeloma
Leukemia (2012)
-
Gene therapy in interventional pulmonology: Interferon gene delivery with focus on thoracic malignancies
Current Respiratory Care Reports (2012)