Wide spectrum of antitumor activity of a neutralizing monoclonal antibody to human vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) is known as an angiogenic factor for tumor angiogenesis. We developed a neutralizing anti-VEGF monoclonal an tibody (MAb), MV833, and examined its antitumor activity against 27 human t umor cell lines transplanted in nude mice. All the tumor cell Lines used in this study secreted various amounts of VEGF into culture medium in vitro. However, the growth of the cell lines, including three which expressed VEGF receptor, was not affected by exogenously added MV833 in vitro. All tumor cell lines including colon, lung, breast, pancreas, and melanoma, grew subc utaneously in nude mice. The growth of HeLa/v5, which had been transformed by human VEGF(121) gene and secreted large amounts of VEGF, was significant ly faster than that of the control vector transformant. Although the amount s of VEGF secreted from two HeLa transformants differed greatly, MV833 comp letely inhibited the growth of both tumors, Moreover, the growth of the oth er 25 human tumor cell lines transplanted into nude mice was also strongly suppressed by MV833. Neither the amount of VEGF secreted from each tumor ce ll line in vitro nor the expression of VEGF receptor correlated with the an titumor activity of MV833. MV833, administered when tumor volumes reached 4 00 mm(3), completely inhibited the growth of some tumor lines. The results show VEGF to be a critical angiogenic factor for many tumors. VEGF-neutrali zing antibody could be applicable as an antitumor agent for a wide range of tumors.