Vasculaturespecific Promoters

Targeting the endothelium of tumors may be amenable to gene therapy. This tissue may be independent of tumor type and is easily accessible to intravascular vector administration. Also, endothelial cells (ECs) are not malignant, and thus are less sensitive to selection pressure and rarely gain resistance to treatment. E-selectin expression is minimal in normal blood vessels but high in the capillaries of tumors, and the promoter was used for driving gene expression in an Ad. Upon infection, EC cell lines expressed high levels of reporter gene expression, whereas non-EC cell lines showed low expression. The addition of TNF-a, an inducer of the promoter, further increased the E-selectin's activity (85). The murine preproendo-thelin-1 (PPE-1) promoter was also used as a TSP for adenovi-ral-mediated delivery to EC cells. Systemic administration to lung tumor-bearing mice resulted in gene expression in the new vasculature of primary tumors (86).

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