Viral vector-mediated transduction of a modified platelet factor 4 cDNA inhibits angiogenesis and tumor growth

Nat Med. 1997 Apr;3(4):437-42. doi: 10.1038/nm0497-437.


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.

Publication types

  • Comparative Study

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / mortality
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Glioblastoma / drug therapy
  • Glioblastoma / mortality
  • Glioma / drug therapy*
  • Glioma / mortality
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Neovascularization, Pathologic / drug therapy*
  • Platelet Factor 4 / genetics
  • Platelet Factor 4 / therapeutic use*
  • Rats
  • Retroviridae / genetics
  • Survival Analysis
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Platelet Factor 4