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 challenges. To overcome these problems for one such protein, we constructed retroviral and adenoviral vectors that express a novel, secretable form of the antiangiogenic protein, platelet factor 4 (sPF4). Vector-mediated sPF4 transduction selectively inhibits endothelial cell proliferation in vitro, and results in hypovascular tumors that grow slowly in vivo. Additionally, tumor-associated angiogenesis is inhibited and animal survival is prolonged, following transduction of established intracerebral gliomas by an sPF4-expressing adenoviral vector. These data support the concept that targeted antiangiogenesis, using virally mediated gene transfer, represents a promising strategy for delivering antiangiogenic therapy.
Tanaka
T
T
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Manome
Y
Y
Wen
P
P
Kufe
D W
DW
Fine
H A
HA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010978:Platelet Factor 4 / Q000235:genetics / Q000627:therapeutic use*; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D016019:Survival Analysis; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D010978:Platelet Factor 4