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Growth inhibition efficacy of an adenovirus expressing dual therapeutic genes, wild-type p53, and anti-erbB2 ribozyme, against human bladder cancer cells

Cancer Gene Therapy volume 13, pages 298–305 (2006)Cite this article

Abstract

The altered expression of both p53 and erbB2 is strongly related to the disease status and the outcome of bladder cancers. We examined the antitumor efficacy by the modulation of these genetic alterations with a newly designed dual-gene-expressing adenovirus (Ad-p53/erbB2Rz), which expresses p53 and anti-erbB2 ribozyme simultaneously in human bladder cancer cells. Cell growth inhibition efficacy along with biological responses of this virus was compared with other viral vectors (Ad-p53, which expresses wild-type p53 cDNA, and Ad-erbB2Rz, which expresses anti-erbB2 ribozyme, solely or in combination). Sufficient transgene expression in targeted cells and the altered expression of the targeted genes and their encoded proteins were obtained by each therapeutic vector. Each of the three therapeutic viral vectors inhibited bladder cancer cell growth, and the putative additive antitumor effect was shown by the combination of two of the therapeutic vectors. Furthermore, Ad-p53/erbB2Rz had superior therapeutic efficacy when the same titers of viruses were infected. Nonspecific vector-related toxicity was minimized by reducing the total amount of viral titers by using the dual-gene-expressing adenovirus. Modulation of multiple genetic abnormalities might enhance the therapeutic efficacy, and vector-related toxicity could be minimized when the total amount of viral titers are reduced.

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Acknowledgements

We thank David Y Bouffard, Olav Engebraaten, Toshiya Suzuki, and Weiqiang Chen for their important suggestions and technical supports.

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Authors and Affiliations

  1. Department of Urology, Kitasato University School of Medicine, Kanagawa, Japan

    A Irie, K Matsumoto, H Kuruma, T Uchida & S Baba

  2. Merz Pharmaceuticals, Frankfurt, Germany

    B Anderegg

  3. University of California San Francisco/Mt. Zion Cancer Center, CA, USA

    M Kashani-Sabet

  4. Keck Graduate Institute, CA, USA

    K J Scanlon

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  1. A Irie
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Correspondence to A Irie.

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Irie, A., Matsumoto, K., Anderegg, B. et al. Growth inhibition efficacy of an adenovirus expressing dual therapeutic genes, wild-type p53, and anti-erbB2 ribozyme, against human bladder cancer cells. Cancer Gene Ther 13, 298–305 (2006). https://doi.org/10.1038/sj.cgt.7700892

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  • DOI: https://doi.org/10.1038/sj.cgt.7700892

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