Antiangiogenic gene therapy of cancer utilizing a recombinant adenovirus to elevate systemic endostatin levels in mice

Gene therapy represents a possible alternative to the chronic delivery of r ecombinant antiangiogenic proteins to cancer patients. Inducing normal host tissues to produce high circulating levels of these proteins may be more e ffective than targeting antiangiogenic genes to tumor tissue specifically. Previously reported gene therapy approaches in mice have achieved peak circ ulating endostatin levels of 8-33 ng/ml. Here we report plasma endostatin l evels of 1770 ng/ml after administration of a recombinant adenovirus. Growt h of MC38 adenocarcinoma, which is relatively resistant to adenoviral infec tion, was inhibited by 40%. These findings encourage gene delivery approach es that use the host as a "factory" to produce high circulating levels of a ntiangiogenic agents.