Anti-VEGF antibody treatment of glioblastoma prolongs survival but results in increased vascular cooption

Neoplasia. Jul-Aug 2000;2(4):306-14. doi: 10.1038/sj.neo.7900102.

Abstract

Vascular endothelial growth factor (VEGF) is an important mediator of the intense angiogenesis which is characteristic of glioblastoma. While genetic manipulation of VEGF/VEGF receptor expression has previously been shown to inhibit glioblastoma growth, to date, no study has examined the efficacy of pharmacologic blockade of VEGF activity as a means to inhibit intracranial growth of human glioblastoma. Using intraperitoneal administration of a neutralizing anti-VEGF antibody, we demonstrate that inhibition of VEGF significantly prolongs survival in athymic rats inoculated in the basal ganglia with G55 human glioblastoma cells. Systemic anti-VEGF inhibition causes decreased tumor vascularity as well as a marked increase in tumor cell apoptosis in intracranial tumors. Although intracranial glioblastoma tumors grow more slowly as a consequence of anti-VEGF treatment, the histologic pattern of growth suggests that these tumors adapt to inhibition of angiogenesis by increased infiltration and cooption of the host vasculature.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies / therapeutic use*
  • Brain Neoplasms / blood supply*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Endothelial Growth Factors / antagonists & inhibitors*
  • Endothelial Growth Factors / immunology
  • Female
  • Glioblastoma / blood supply*
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Humans
  • In Situ Nick-End Labeling
  • Lymphokines / antagonists & inhibitors*
  • Lymphokines / immunology
  • Neovascularization, Pathologic / prevention & control*
  • Rats
  • Rats, Nude
  • Survival Rate
  • Time Factors
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Antibodies
  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors