Retroviral vector-producer cell mediated angiogenesis inhibition restrictsneuroblastoma growth in vivo

Background. The purpose of this study was to determine whether gene therapy -mediated delivery of an angiogenesis inhibitor, a truncated, soluble vascu lar endothelial growth factor receptor (Flk-1/KDR, VEGFR-2), could suppress tumor growth in a murine model of neuroblastoma. Methods. Murine fibroblas ts producing a replication-defective retrovirus encoding this mutant form o f flk-1 were made. These producer cells were mixed with neuroblastoma cells and injected subcutaneously into SCID mice. Subsequent tumor growth was th en measured. Results. Murine neuroblastoma growth was decreased by 95% afte r 25 days. Similar tumor growth inhibitory effects were observed when the f lk-1 producer cells were co-injected with cells from two different human ne uroblastoma cell lines. Conclusions. Neuroblastoma growth can be significan tly restricted in vivo with a single injection of cells that produce a retr oviral Vector encoding the gene for an angiogenesis inhibitor. This suggest s that gene therapy-mediated delivery can be an effective alternative to ch ronic administration of these cytostatic anticancer agents. Med. Pediatr. O ncol. 35:638-640, 2000. (C) 2000 Wiley-Liss. Inc.