Antibodies for angiogenesis inhibition, vascular targeting and endothelial cell transcytosis

The endothelium is increasingly recognized as a target for biomedical intervention, not only for its accessibility to molecular agents coming from the blood-stream, but also for the active role played by endothelial cell proliferation to support diseases such as cancer, blinding ocular disorders and chronic inflammatory conditions. The notion that solid tumors cannot grow beyond a size of few millimeters without inducing the proliferation of new blood vessels has stimulated the search for mediators of angiogenesis and for inhibitors of this process, culminating in the approval of a humanized monoclonal antibody to VEGF-A for oncology applications. In parallel, researchers have begun to consider imaging and therapeutic strategies based on the selective delivery of bioactive agents to the new blood vessels, mediated by monoclonal antibody derivatives. Recently, the field of vascular targeting research has been extended to the investigation of molecular agents that may mediate endothelial cell transcytosis, in the hope to overcome this body barrier for drug delivery. This article reviews some of the most significant advances in these areas, and outlines future challenges and opportunities. (c) 2006 Elsevier B.V. All rights reserved.