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Efficacy of a single intravesical treatment with Ad-IFN/Syn 3 is dependent on dose and urine IFN concentration obtained: implications for clinical investigation

Cancer Gene Therapy volume 13, pages 125–130 (2006)Cite this article

Abstract

There is a need to improve the treatment of superficial bladder cancer. One area which holds promise is intravesical gene therapy. Recently, studies undertaken by us have shown that marked tumor regression of bladder cancers occurred after two daily intravesical administrations of an adenovirus encoding human interferon α (Ad-IFNα) using a mouse superficial bladder cancer model in which human bladder tumors are growing. A dose of 1 × 1011 particles/ml (P/ml) was used along with 1 mg/ml of Syn3, a gene transfer-enhancing agent. Since clinical studies are being planned using this approach, it became critical to determine if one exposure and lower particle number could be equally effective. We report that indeed a single dose of Ad-IFNα in Syn3 at doses of 1 × 1010–1 × 1011 P/ml is highly effective in reducing the size of the tumors, whereas 1 × 109 P/ml was not. Efficacy was also correlated with the level of IFN produced in the urine after treatment. Based on the results of the present studies, a Phase I trial is being planned for superficial bladder cancer, which will involve a single initial treatment with Ad-IFNα/Syn3 and measurement of IFN in the urine over time as an indicator of adequate gene transfer and expression.

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Acknowledgements

We thank Dr Daniel Maneval for his review of this manuscript and helpful comments. This work was supported by the GU SPORE Grant P50 CA091846 and the Cancer Center Support (Core) Grant CA16672 from the NIH.

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Authors and Affiliations

  1. Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Z Tao, F Ashoori & W F Benedict

  2. Canji, Incorporated, San Diego, CA, USA

    R J Connor & J A Philopena

  3. Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    C P N Dinney

  4. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Munsell

Authors
  1. Z Tao
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  2. R J Connor
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  3. F Ashoori
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  6. J A Philopena
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  7. W F Benedict
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Correspondence to W F Benedict.

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Tao, Z., Connor, R., Ashoori, F. et al. Efficacy of a single intravesical treatment with Ad-IFN/Syn 3 is dependent on dose and urine IFN concentration obtained: implications for clinical investigation. Cancer Gene Ther 13, 125–130 (2006). https://doi.org/10.1038/sj.cgt.7700865

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