Retroviral vector-producer cell mediated angiogenesis inhibition restricts neuroblastoma growth in vivo.
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.
Davidoff
A M
AM
Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. andrew.davidoff@stjude.org
Leary
M A
MA
Ng
C Y
CY
Vanin
E F
EF
D000818:Animals; D002455:Cell Division; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D017978:Receptors, Growth Factor / Q000235:genetics*; D011975:Receptors, Mitogen / Q000235:genetics*; D040262:Receptors, Vascular Endothelial Growth Factor; D012190:Retroviridae; D013997:Time Factors; D014407:Tumor Cells, Cultured
D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor