T. Tanaka et al., VIRAL VECTOR-MEDIATED TRANSDUCTION OF A MODIFIED PLATELET FACTOR-4 CDNA INHIBITS ANGIOGENESIS AND TUMOR-GROWTH, Nature medicine, 3(4), 1997, pp. 437-442
Citations number
30
Categorie Soggetti
Medicine, Research & Experimental",Biology,"Cell Biology
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.