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Cancer Lett. 2016 Jul 28;377(2):164-73. doi: 10.1016/j.canlet.2016.04.036. Epub 2016 Apr 26.

Dual blockade of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2) exhibits potent anti-angiogenic effects.

Author information

1
School of Life Sciences and Technology, Tongji University, Shanghai, China.
2
Yantai RC Biotechnologies, Ltd., Yantai, Shandong, China.
3
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.

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.

KEYWORDS:

Angiogenesis; Anti-angiogenic therapy; Cancer therapy; Dual decoy receptor; FGF-2; VEGF

PMID:
27130666
DOI:
10.1016/j.canlet.2016.04.036
[Indexed for MEDLINE]

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