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 angiogenic promoter present in a wide variety of human tumors. VEGF is expressed as 4 isoforms; one of these, VEGF165, predominates in human tumors. The authors hypothesized that antagonism of VEGF165 by a specific aptamer would block tumor growth in an experimental model of Wilms tumor. Methods: VEGF isoform expression in clinical (n = 2) and experimental tumors 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 animals (0.69 v 4.41 g; P < .028), without observed adverse effects and similar to suppression previously reported using nonisoform-specific anti-VEGF antibody (94% to 96%). Conclusions: Anti-VEGF165 aptamer effectively suppressed primary tumor growth in experimental animals with no observed adverse effects. Development of highly specific antiangiogenic therapies may be of particular benefit to pediatric patients. Copyright (C) 2001 by W.B. Saunders Company.