VEGF-Trap: A VEGF blocker with potent antitumor effects

被引：1336

作者：

Holash, J ^{[1
]}

Davis, S ^{[1
]}

Papadopoulos, N ^{[1
]}

Croll, SD ^{[1
]}

Ho, L ^{[1
]}

Russell, M ^{[1
]}

Boland, P ^{[1
]}

Leidich, R ^{[1
]}

Hylton, D ^{[1
]}

Burova, E ^{[1
]}

Ioffe, E ^{[1
]}

Huang, T ^{[1
]}

Radziejewski, C ^{[1
]}

Bailey, K ^{[1
]}

Fandl, JP ^{[1
]}

Daly, T ^{[1
]}

Wiegand, SJ ^{[1
]}

Yancopoulos, GD ^{[1
]}

Rudge, JS ^{[1
]}

机构：

[1] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2002年 / 99卷 / 17期

关键词：

D O I：

10.1073/pnas.172398299

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Vascular endothelial growth factor (VEGF) plays a critical role during normal embryonic angiogenesis and also in the pathological angiogenesis that occurs in a number of diseases, including cancer. Initial attempts to block VEGF by using a humanized monoclonal antibody are beginning to show promise in human cancer patients, underscoring the importance of optimizing VEGF blockade. Previous studies have found that one of the most effective ways to block the VEGF-signaling pathway is to prevent VEGF from binding to its normal receptors by administering decoy-soluble receptors. The highest-affinity VEGF blocker described to date is a soluble decoy receptor created by fusing the first three Ig domains of VEGF receptor 1 to an Ig constant region; however, this fusion protein has very poor in vivo pharmacokinetic properties. By determining the requirements to maintain high affinity while extending in vivo half life, we were able to engineer a very potent high-affinity VEGF blocker that has markedly enhanced pharmacokinetic properties. This VEGF-Trap effectively suppresses tumor growth and vascularization in vivo, resulting in stunted and almost completely avascular tumors. VEGF-Trap-mediated blockade may be superior to that achieved by other agents, such as monoclonal antibodies targeted against the VEGF receptor.

引用

页码：11393 / 11398

页数：6

共 36 条

[1] INCREASED VASCULAR ENDOTHELIAL GROWTH-FACTOR LEVELS IN THE VITREOUS OF EYES WITH PROLIFERATIVE DIABETIC-RETINOPATHY [J].