Tumors 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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The authors thank Karel Petrak, Michael Fons, Jeff Nordstrom, Federica Pericle, and Norman Hardman for helpful discussion and critical review of the manuscript; and the Department of Integrated Manufacturing and Quality Control for supplying the plasmids.
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Blezinger, P., Wang, J., Gondo, M. et al. Systemic inhibition of tumor growth and tumor metastases by intramuscular administration of the endostatin gene. Nat Biotechnol 17, 343–348 (1999). https://doi.org/10.1038/7895
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