Nature Biotechnology
17, 343 - 348 (1999)
doi:10.1038/7895
Systemic inhibition of tumor growth and tumor metastases by intramuscular
administration of the endostatin genePaul Blezinger, Jijun Wang, Margaret Gondo, Abraham Quezada, Dorothy Mehrens, Martha French, Arun Singhal, Sean Sullivan, Alain Rolland, Rob Ralston
& Wang Min
GeneMedicine, Inc., 8301 New Trails Dr.
, The Woodlands, TX 77381-4248.
Correspondence should be addressed to Wang Min minw@genemedicine.comangiogenesisendostatingene therapycancerintramuscular deliveryTumors require ongoing angiogenesis to support their growth. Inhibition
of angiogenesis by production of angiostatic factors should be a viable approach
for cancer gene therapy. Endostatin, a potent angiostatic factor, was expressed
in mouse muscle and secreted into the bloodstream for up to 2 weeks after
a single intramuscular administration of the endostatin gene. The biological
activity of the expressed endostatin was demonstrated by its ability to inhibit
systemic angiogenesis. Moreover, the sustained production of endostatin by
intramuscular gene therapy inhibited both the growth of primary tumors and
the development of metastatic lesions. These results demonstrate the potential
utility of intramuscular delivery of an antiangiogenic gene for treatment
of disseminated cancers.
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