VEGF-VEGF receptor complexes as markers of tumor vascular endothelium

Vascular endothelial growth factor (VEGF) is a primary stimulant of the vas cularization of solid tumors and has therefore been the focus of intense re search aimed at blocking its activity in solid tumors. VEGF production by t umor cells is induced by oncogenic gene mutations and hypoxic conditions in side the tumor mass. VEGF receptor expression on endothelial cells lining b lood vessels in the tumor is also induced by hypoxia and the increased loca l concentration of VEGF. Therefore in the tumor microenvironment there is a n upregulation of both VEGF and its receptor leading to a high concentratio n of occupied receptor on tumor vascular endothelium. The VEGF-VEGF recepto r complex (VEGF-VEGFR) presents an attractive target for the specific deliv ery of drugs or other effectors to tumor endothelium. Herein we review the development of monoclonal antibodies that selectively bind to the VEGF-VEGF R and their use as targeting agents that selectively bind to VEGF activated blood vessels. Additionally, we summarize the properties of 2C3, a novel m onoclonal anti-VEGF antibody that blocks VEGF from binding to VEGFR2 but no t VEGFR1. 2C3 may be utilized as both an anti-angiogenic agent by inhibitin g VEGFR2 activity and potentially as a vascular targeting agent by binding to blood vessels that express the VEGF-VEGFR1 complex. (C) 2001 Elsevier Sc ience B.V. All rights reserved.