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融合蛋白:阿柏西普(VEGF Trap-Eye)。

Fusion Proteins: Aflibercept (VEGF Trap-Eye).

作者信息

Sarwar Salman, Bakbak Berker, Sadiq Mohammad Ali, Sepah Yasir J, Shah Syed Mahmood, Ibrahim Mohamed, Do Diana V, Nguyen Quan Dong

出版信息

Dev Ophthalmol. 2016;55:282-94. doi: 10.1159/000439008. Epub 2015 Oct 26.

Abstract

Vascular endothelial growth factor (VEGF) inhibitors currently used to treat eye diseases have included monoclonal antibodies, antibody fragments, and an aptamer. A different method of achieving VEGF blockade in retinal diseases includes the concept of a cytokine trap. Cytokine traps are being evaluated for the treatment of various diseases that are driven by excessive cytokine levels. Traps, such as VEGF Trap, consist of two extracellular cytokine receptor domains fused together to form a human IgG. Aflibercept (VEGF Trap-Eye) is a soluble fusion protein which combines ligand-binding elements taken from the extracellular components of VEGF receptor (VEGFR)-1 and VEGFR-2 fused to the Fc portion of IgG. This protein contains all human amino-acid sequences, which minimizes the potential for immunogenicity in human patients. The chapter will summarize the chemical properties of aflibercept and the various studies that have demonstrated a role of aflibercept in the management of retinal vascular diseases such as neovascular age-related macular degeneration, diabetic retinopathy, macular edema, and retinal vein occlusion.

摘要

目前用于治疗眼部疾病的血管内皮生长因子(VEGF)抑制剂包括单克隆抗体、抗体片段和适配体。在视网膜疾病中实现VEGF阻断的另一种方法包括细胞因子陷阱的概念。细胞因子陷阱正在被评估用于治疗由细胞因子水平过高驱动的各种疾病。诸如VEGF Trap之类的陷阱由两个融合在一起形成人IgG的细胞外细胞因子受体结构域组成。阿柏西普(VEGF Trap-Eye)是一种可溶性融合蛋白,它结合了取自血管内皮生长因子受体(VEGFR)-1和VEGFR-2细胞外成分的配体结合元件,并与IgG的Fc部分融合。这种蛋白质包含所有人类氨基酸序列,从而将人类患者产生免疫原性的可能性降至最低。本章将总结阿柏西普的化学性质以及各种证明阿柏西普在治疗视网膜血管疾病(如新血管性年龄相关性黄斑变性、糖尿病性视网膜病变、黄斑水肿和视网膜静脉阻塞)中作用的研究。

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