Cancer metastasis accounts for a significant proportion of morbidity and mortality in patients. Effective means of treating disseminated disease remains elusive. The purpose of this study was to determine whether genetically modified endothelial cells ( GMEC ) can selectively target and deliver recombinant therapeutic molecules to sites of tumor metastases. Following the establishment of lung metastases of 4T1 mammary tumor in mice, intravenously ( i.v. ) administered, lacZ transgene -expressing endothelial cells ( lacZ -GMEC ) accumulated at the tumor sites. An average of 32% and 90% of the pulmonary metastases were X -gal stained following one and three tail vein injections of 10 5 lacZ -GMEC, respectively. The linear pattern of X -gal staining seen within the tumor sites and the histological appearance of the tumor vasculature were consistent with the incorporation of lacZ -GMEC into blood vessels. In C57Bl / 6 mice harboring lung metastases of melanoma, the administration of three sequential i.v. injections of 10 5 endothelial cells expressing a human interleukin 2 transgene abrogated the tumor metastases and prolonged survival of the animals. These results demonstrate that i.v. -administered GMEC can selectively accumulate, survive, and stably express exogenous genes at multiple tumor sites. These findings support a role for i.v. -administered GMEC as a potential therapeutic strategy for the systemic treatment of cancer metastases. Cancer Gene Therapy ( 2001 ) 8, 636 -648
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