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Treatment of intracranial glioma with in situ interferon-gamma and tumor necrosis factor-alpha gene transfer

Cancer Gene Therapy volume 9, pages 925–934 (2002)Cite this article

Abstract

Interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα) are potent immunostimulatory cytokines with demonstrated tumoricidal effects in a variety of cancers. With the aim of investigating their ability to generate antitumor immune responses in malignant brain tumors, we describe the use of in situ adenoviral-mediated IFNγ and TNFα gene transfer in glioma-bearing rodents. Survival was prolonged in mice treated with AdmIFNγ or AdTNFα compared to AdLacZ- and saline-inoculated controls, and AdmIFNγ- or AdTNFα-treated animals revealed significantly smaller tumors. These effects were accompanied by significant up-regulation of tumor MHC-I expression in AdmIFNγ-inoculated animals, and of MHC-II in AdTNFα-treated tumors. Significantly enhanced intratumoral infiltration with CD4+ and CD8+ T cells was visible in animals treated with AdmIFNγ, AdTNFα, or a combination of AdmIFNγ and AdTNFα. In addition, AdTNFα therapy down-regulated the expression of endothelial Fas ligand, a cell membrane protein implicated as a contributor to immune privilege in cancer. These findings demonstrate the effectiveness of local IFNγ and TNFα gene transfer as a treatment strategy for glioma and illustrate possible physiological pathways responsible for the therapeutic benefit observed.

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Acknowledgements

This work was supported, in part, by NIH Grant NS02232 to John S Yu.

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Authors and Affiliations

  1. Maxine Dunitz Neurosurgical Institute, Cedars-Sinai Medical Center, Los Angeles, 90048, California, USA

    Moneeb Ehtesham, Ken Samoto, Peter Kabos, Frank L Acosta, Mervin AR Gutierrez, Keith L Black & John S Yu

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  1. Moneeb Ehtesham
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Correspondence to John S Yu.

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Ehtesham, M., Samoto, K., Kabos, P. et al. Treatment of intracranial glioma with in situ interferon-gamma and tumor necrosis factor-alpha gene transfer. Cancer Gene Ther 9, 925–934 (2002). https://doi.org/10.1038/sj.cgt.7700516

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