Coelectrotransfer to skeletal muscle of three plasmids coding for antiangiogenic factors and regulatory factors of the tetracycline-inducible system: tightly regulated expression, inhibition of transplanted tumor growth, and antimetastatic effect.

We describe an approach employing intramuscular plasmid electrotransfer to deliver secretable forms of K1-5 and K1-3-HSA (a fusion of K1-3 with human serum albumin), which span, respectively, five and three of the five kringle domains of plasminogen. A tetracycline-inducible system (Tet-On) composed of three plasmids coding, respectively, for the transgene, the tetracycline transcriptional activator rtTA, and the silencer tTS was employed. K1-3-HSA and K1-5, produced from C2C12 muscle cells, were found to inhibit endothelial cell (HMEC-1) proliferation by 30 and 51%, respectively.

Combined effects of docetaxel and angiostatin gene therapy in prostate tumor model.

The anti-tumor effects of adenovirus-delivered angiostatin (AdK3) in association with docetaxel (Taxotere) have been evaluated in a human-origin prostate tumor model. In vitro, human endothelial cells were 50- to 100-fold more sensitive to docetaxel than prostate cell lines (PC3, LNCaP, and DU145), and the combination regimen of docetaxel and AdK3 was significantly more cytotoxic for endothelial cells than either treatment alone. PC3 cells, which display the highest sensitivity to docetaxel, were then grafted onto athymic mice for an evaluation of the combined regimen as a therapy.