| abstract |
The present invention relates to methods and vectors for gene therapy of tumors. Intratumoral, adenovirus-mediated administration of antiangiogenic factors achieves potential antitumor effects by targeting angiogenesis. The present invention is based on the gene therapy targeting of a urokinase amino-terminal fragment (ATF) and angiostatin. To determine its role in tumor growth and spread, a defective adenovirus (AdmATF) capable of expressing murine ATF under the control of a CMV promoter is produced. A single intratumoral injection of AdmATF inhibited the growth of a previously formed tumor in two different rodent models and delayed tumor spread, inhibiting aneovascularization at the injection site and its immediate vicinity. Rodent-derived ATF was able to inhibit angiogenesis of human tumors. In addition, a defective adenovirus (AdK3) capable of expressing the N-terminal fragment of human plasminogen is generated and its activity in vitro and in vivo in various rodent tumor models. The AdK3 vector inhibited tumor growth, tumor angiogenesis, and induced tumor cell apoptosis. SHE |