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The flt-1 Promoter for Transcriptional Targeting of Teratocarcinoma¹

Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, University of Alabama at Birmingham, Birmingham, Alabama 35294 [G. J. B., D. M. N., A. K., A. H., P. N. R., D. T. C.], and Department of Medicine and Therapeutics, University of Glasgow, Glasgow, GI1 GNT, Scotland, United Kingdom [A. H. B.]

Flt-1, a receptor for vascular endothelial growth factor, is known to display dysregulated expression in both tumor vasculature and tumor cells per se, suggesting that the flt-1 promoter might be a useful candidate to achieve tumor-specific transgene expression. In addition, adenoviral vectors containing transgenes under the control of the flt-1 promoter achieve very low levels of expression in the normal liver, the major organ responsible for blood clearance of adenoviruses and inadvertent transgene-related toxicity. Thus, we assessed the ability of adenoviral vectors containing the flt-1 promoter to achieve transgene expression in a range of gynecological and breast tumor lines. High transgene expression levels were detected in teratocarcinoma lines, correlating with levels of flt-1 mRNA. These results suggest that the flt-1 promoter could be useful for transcriptionally targeted gene expression to teratocarcinoma, and that evaluation in other flt-1-positive tumors is warranted.