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Gene therapy with Apoptin induces regression of xenografted human hepatomas

Cancer Gene Therapy volume 9, pages 53–61 (2002)Cite this article

Abstract

The chicken anemia virus–derived Apoptin protein shows remarkable specificity; namely, it induces apoptosis in tumor cells, but not in normal diploid cells. We have exploited the Apoptin gene for use in cancer gene therapy. Here we demonstrate that adenovirus-mediated intratumoral transfer and expression of the Apoptin gene results in regression or complete remission of human hepatomas grown as xenografts in immune-deficient mice, and significantly increases their survival long term. Early after intratumoral injection, Apoptin could be detected in significant quantities by Western blot analyses and immunohistochemistry. Furthermore, cell death and disruption of the tumor integrity were apparent in the transduced regions. This experimental gene therapeutic strategy constitutes a unique example of specific antitumor activity using a virus-derived gene with broad-spectrum applicability.

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Acknowledgements

The authors gratefully thank S Le Cessie (Department of Medical Statistics, Leiden University) for statistical analysis, and Dr. PM Voorhoeve and Dr. JL Rohn for critical review of the manuscript and stimulating discussions. This work was supported by a research Grant from the Netherlands Ministry of Economic Affairs.

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Author notes

  1. Marjolijn M van der Eb and Alexandra M Pietersen: Both authors contributed equally to this paper and should both be considered to be “first author.”

Authors and Affiliations

  1. Department of Molecular Cell Biology, Leiden University Medical Centre, Leiden, 2333, AL, The Netherlands

    Marjolijn M van der Eb, Alexandra M Pietersen, Mathieu HM Noteborn & Rob C Hoeben

  2. Department of Surgery, Leiden University Medical Centre, Leiden, 2333, AL, The Netherlands

    Marjolijn M van der Eb, Frank M Speetjens, Peter JK Kuppen & Cornelis JH van de Velde

  3. Leadd BV, Leiden, The Netherlands

    Alexandra M Pietersen & Mathieu HM Noteborn

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  1. Marjolijn M van der Eb
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Correspondence to Mathieu HM Noteborn.

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van der Eb, M., Pietersen, A., Speetjens, F. et al. Gene therapy with Apoptin induces regression of xenografted human hepatomas. Cancer Gene Ther 9, 53–61 (2002). https://doi.org/10.1038/sj.cgt.7700397

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