M200, an integrin α5β1 antibody, promotes apoptosis in proliferating endothelial cells

Abstract

3187 Background: The role of VEGF in mediating angiogenesis is well documented, but recent evidence indicates that integrins such as αvβ3 are also important. We identified α5 integrin using a proprietary gene array. The α5β1 integrin mediates the binding of endothelial cells to fibronectin in the extracellular matrix. The growth factors VEGF and bFGF also promote the recruitment of new blood vessels into expanding tumors. We assessed the relative roles of these factors in vitro and in vivo to elucidate the validity of inhibiting integrin α5β1. Methods: We measured affinity of a chimeric antibody, M200, against α5β1 integrin by BIAcore, and assessed the role of α5β1 using an in vitro angiogenesis model and in vivo in a laser-induced model of choroidal neovascularisation (CNV) in cynomolgus monkeys. We compared M200 to an anti-VEGF mAb for effects on endothelial cell survival and proliferation in vitro. Results: M200, and its derivative Fab F200, inhibit binding of fibronectin to α5β1. M200 and F200 have si...