title: Dual blockade of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) exhibits potent anti-angiogenic effects.
abstract: Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF or FGF-2) are potent pro-angiogenic factors and play a critical role in cancer development and progression. Clinical anti-VEGF therapy trials had a major challenge due to upregulated expression of other pro-angiogenic factor, like FGF-2. This study developed a novel chimeric decoy receptor VF-Trap fusion protein to simultaneously block activity of both VEGF and FGF pathways in order to achieve an additive or synergistic anti-tumor effect. Our in vitro data showed that VF-Trap potently blocked proliferation and migration of both VEGF- and FGF-2-induced vascular endothelial cells. In animal models, treatment of xenograft tumors with VF-Trap resulted in significant inhibition of tumor growth compared to blockage of the single molecule, like VEGF or FGF blocker. In addition, VF-Trap was also more potent in inhibition of ocular angiogenesis in a mouse oxygen-induced retinopathy (OIR) model. These data demonstrated the potent anti-angiogenic effects of this novel VF-Trap fusion protein on blockage of VEGF and FGF-2 activity in vitro and in animal models. Further study will assess its effects in clinic as a therapeutic agent for angiogenesis-related disorders, such as cancer and ocular vascular diseases.
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Xie
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Longzhen
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Xuejing
authors.initials: X
authors.lastname: Yao
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Hongwen
authors.initials: H
authors.lastname: Li
authors.affiliation: Yantai RC Biotechnologies, Ltd., Yantai, Shandong, China.
authors.forename: Qiaoyu
authors.initials: Q
authors.lastname: Xu
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Yantai RC Biotechnologies, Ltd., Yantai, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jiang
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai, China; Yantai RC Biotechnologies, Ltd., Yantai, Shandong, China; Tongji University Suzhou Institute, Suzhou, Jiangsu, China; Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, China. Electronic address: jfang@tongji.edu.cn.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
mesh_terms: D000072283:A549 Cells; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D016466:CHO Cells; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003412:Cricetulus; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D018496:Hyperoxia / Q000150:complications; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D015861:Retinal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D020533:Angiogenesis Inhibitors; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D016222:Fibroblast Growth Factor 2
keywords: Angiogenesis; Anti-angiogenic therapy; Cancer therapy; Dual decoy receptor; FGF-2; VEGF