Highly specific antiangiogenic therapy is effective in suppressing growth of experimental Wilms tumors

Background/Purpose: Pathologic angiogenesis in tumors is a potential target for novel therapies. Vascular endothelial growth factor (VEGF) is an angio genic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The au thors hypothesized that antagonism of VEGF165 by a specific aptamer would b lock tumor growth in an experimental model of Wilms tumor. Methods: VEGF isoform expression in clinical (n = 2) and experimental tumor s were evaluated by reverse transcription polymerase chain reaction (RT-PCR ). Tumors were induced in NCR nude mice (n = 32) by intrarenal injection of 10(6) cultured Wilms tumor cells. At 1 week, aptamer (n = 16) or vehicle ( n = 16) treatment was started and continued daily for 5 weeks. Results: At 6 weeks tumors weighed 84% less in treated versus control anima ls (0.69 v 4.41 g; P < .028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF anti body (94% to 96%). Conclusions: Anti-VEGF165 aptamer effectively suppressed primary tumor grow th in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to p ediatric patients. Copyright (C) 2001 by W.B. Saunders Company.