Retroviral vector-producer cell mediated angiogenesis inhibition restricts neuroblastoma growth in vivo |
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Authors: | Davidoff A M Leary M A Ng C Y Vanin E F |
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Affiliation: | Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. andrew.davidoff@stjude.org |
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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. |
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