VIRAL VECTOR-MEDIATED TRANSDUCTION OF A MODIFIED PLATELET FACTOR-4 CDNA INHIBITS ANGIOGENESIS AND TUMOR-GROWTH

Chronic systemic delivery of therapeutic proteins, such as inhibitors of angiogenesis, present a number of difficult pharmacological challen ges. To overcome these problems for one such protein, we constructed r etroviral and adenoviral vectors that express a novel, secretable form of the antiangiogenic protein, platelet factor 4 (sPF4). Vector-media ted sPF4 transduction selectively inhibits endothelial cell proliferat ion in vitro, and results in hypovascular tumors that grow slowly in v ivo. Additionally, tumor-associated angiogenesis is inhibited and anim al survival is prolonged, following transduction of established intrac erebral gliomas by an sPF4-expressing adenoviral vector. These data su pport the concept that targeted antiangiogenesis, using virally mediat ed gene transfer, represents a promising strategy for delivering antia ngiogenic therapy.