Potential therapeutic use of anti-Flt1 antibodies

We describe the generation and intensive characterization of mAb AA98, including its functional properties, and its antigen identification. In our study, an enhanced mAb AA98-immunoreactivity was observed on stimulated human umbilical vein endothelial cells (HUVEC). In addition, mAb AA98 showed remarkably restricted immunoreactivity against intratumoral neovasculature compared to blood vessels of normal tissues. We identified the AA98-antigen as human CD146, an adhesion molecule belonging to the immunoglobulin superfamily. Data from in vitro experiments imply structural and signaling functions for endothelial CD146, however, the role of CD146 in vivo is largely unknown. Here, we show that mAb AA98 displays anti-angiogenic properties in vitro and in vivo. Proliferation and migration of HUVECs were inhibited by mAb AA98 as was angiogenesis in chicken chorioallantoic membrane (CAM) assays and tumor growth in three xenografted human tumor models in mice. Our data provide new insights into the function of CD146 on endothelial cells, validate CD146 as a novel target for antiangiogenic agents, and demonstrate that mAb AA98 has potential as a diagnostic and therapeutic agent in vascular and cancer biology.