Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene

Tumors require ongoing angiogenesis to support their growth, Inhibition of angiogenesis by production of angiostatic factors should be a viable approa ch for cancer gene therapy. Endostatin, a potent angiostatic factor, was ex pressed in mouse muscle and secreted into the bloodstream for up to 2 weeks after a single intramuscular administration of the endostatin gene. The bi ological activity of the expressed endostatin was demonstrated by its abili ty to inhibit systemic angiogenesis. Moreover, the sustained production of endostatin by intramuscular gene therapy inhibited both the growth of prima ry tumors and the development of metastatic lesions. These results demonstr ate the potential utility of intramuscular delivery of an antiangiogenic ge ne for treatment of disseminated cancers.