4.6 Article

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

Journal

CANCER GENE THERAPY
Volume 13, Issue 2, Pages 125-130

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cgt.7700865

Keywords

bladder cancer; intravesical therapy; interferon

Funding

  1. NCI NIH HHS [CA16672, P50 CA091846] Funding Source: Medline

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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 alpha (Ad-IFN alpha) using a mouse superficial bladder cancer model in which human bladder tumors are growing. A dose of 1 x 10(11) 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-IFNa in Syn3 at doses of 1 x 10(10)-1 x 10(11) P/ml is highly effective in reducing the size of the tumors, whereas 1 x 10(9) 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-IFN alpha/Syn3 and measurement of IFN in the urine over time as an indicator of adequate gene transfer and expression.

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