P. Blezinger et al., Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene, NAT BIOTECH, 17(4), 1999, pp. 343-348
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.