Combined VEGF and alphavbeta3 targeting in ovarian carcinoma

281 Objectives: Based on mechanistic studies, we tested the efficacy of dual targeting of Vascular Endothelial Growth Factor (VEGF) and the alphavbeta3 integrin (αvβ3) in orthotopic mouse models of ovarian cancer.
 Methods: In vivo therapy experiments were carried out in chemo-sensitive (SKOV3ip1, HeyA8) and -resistant (SKOV3TRip2) ovarian cancer cell lines. VEGF was targeted with bevacizumab (Avastin, Genentech) and αvβ3 with the fully humanized monoclonal antibody MEDI-522 (Abegrin, MedImmune, Inc.). Mice were treated with each agent alone, together, or combined with paclitaxel for assessment of tumor growth. Tumor specimens were also tested for proliferative index by proliferative nuclear cell antigen (PCNA), microvessel density by CD31, and tumor cell apoptosis by TUNEL.
 Results: We have previously characterized VEGF production and alphavbeta3 expression in these cell lines. In the SKOV3ip1 model, both single-agent bevacizumab and MEDI-522 reduced tumor growth by 52-63% (p