Retroviral vector-producer cell mediated angiogenesis inhibition restricts neuroblastoma growth in vivo

Med Pediatr Oncol. 2000 Dec;35(6):638-40. doi: 10.1002/1096-911x(20001201)35:6<638::aid-mpo33>3.0.co;2-q.

Abstract

Background: The purpose of this study was to determine whether gene therapy-mediated delivery of an angiogenesis inhibitor, a truncated, soluble vascular endothelial growth factor receptor (Flk-1/KDR, VEGFR-2), could suppress tumor growth in a murine model of neuroblastoma.

Methods: Murine fibroblasts producing a replication-defective retrovirus encoding this mutant form of flk-1 were made. These producer cells were mixed with neuroblastoma cells and injected subcutaneously into SCID mice. Subsequent tumor growth was then measured.

Results: Murine neuroblastoma growth was decreased by 95% after 25 days. Similar tumor growth inhibitory effects were observed when the flk-1 producer cells were co-injected with cells from two different human neuroblastoma cell lines.

Conclusions: Neuroblastoma growth can be significantly restricted in vivo with a single injection of cells that produce a retroviral vector encoding the gene for an angiogenesis inhibitor. This suggests that gene therapy-mediated delivery can be an effective alternative to chronic administration of these cytostatic anticancer agents.

Publication types

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

MeSH terms

  • Animals
  • Cell Division
  • Genetic Vectors*
  • Humans
  • Mice
  • Neovascularization, Pathologic*
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology*
  • Neuroblastoma / therapy
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptors, Growth Factor / genetics*
  • Receptors, Mitogen / genetics*
  • Receptors, Vascular Endothelial Growth Factor
  • Retroviridae*
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Receptors, Growth Factor
  • Receptors, Mitogen
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor