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工業技術研究院

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技術名稱: 抗人類輸鐵蛋白受體的單域抗體與其應用

技術簡介

由於惡性細胞多大量表現輸鐵蛋白受體,且此受體位於細胞表面上,具有易結合、偵測及為細胞內噬作用(endocytosis)媒介的特性,因此,輸鐵蛋白受體(transferrin receptor,TfR) 已被視為一對於癌症標靶治療之有效標的。我們從人類單域抗體庫中篩選出對人類輸鐵蛋白受體具結合力的單域抗體,分別為VHA3 和 VHD4。為增加抗原-抗體結合親合力,以基因重組方式融合人類IgG的Fc區域形成二價VH-Fc抗體,分別命名為VHA3Fc及VHD4Fc。藉由酵素免疫吸附分析法(ELISA)來測定二價抗體對人類輸鐵蛋白受體的結合親合力。VHA3Fc抗體與VHD4F對於人類輸鐵蛋白受體的解離平衡常數(KD)分別為約280與約330 nM 。此外,也證實該二價抗體具誘導K562細胞內噬作用能力,並發現可輕微的抑制腫瘤細胞株生長。

Abstract

The transferring receptor (TfR) has been explored as a target to deliver therapeutics into cancer cells due to its increased expression level on malignant cells, accessibility on the cell surface, and constitutive endocytosis. In this work, we have isolated anti-human TfR domain antibodies, VHA3 and VHD4, from a human single domain antibody library. To increase antigen-antibody binding affinity, we engineered bivalent antibody format (named VHA3Fc and VHD4Fc respectively) by adding a human fragment crystallizable region (Fc region). We determined the binding properties of bivalent antibodies to the hTfR by ELISA. The equilibrium constant (KD) values of approximately 280 and 330 nM were obtained for VHA3Fc and VHD4Fc. Moreover, we have confirmed the antibodies targeted to K562 cells and resulted in endocytosis by flow cytometry. We also found bivalent antibodies displayed slight inhibitory effect on the growth of cancer cell lines.

技術規格

為全人源抗體序列。 2.該抗體具有與人類輸鐵蛋白受體專一性結合的能力。 3.抗體可藉由一受體媒介內噬作用進入一細胞中。 4.VHA3Fc抗體與VHD4Fc對於人類輸鐵蛋白受體的解離平衡常數(KD)分別為約280與約330 nM。

Technical Specification

Fully human antibody sequence. 2.The anti-human transferrin receptor antibody is capable of specifically binding to a human transferrin receptor. 3.The anti-human transferrin receptor antibody is capable of entering a cell through receptor-mediated endocytosis. 4.The equilibrium constant (KD) values of VHA3Fc antibody and VHD4Fc antibody to human transferrin receptor were approximately 280 and 330 nM, respectively.

技術特色

1.本案人類輸鐵蛋白受體抗體在heavy chain variable region序列為獨有,與先前技術不同。 2.本案抗體序列來源為人類,先前技術為鼠源。人體易產生HAMA (Human anti-mouse antibodies) 來中和鼠源的抗體而使失去療效。 3.本案抗體可誘導人類血癌細胞內噬作用,未來可應用於腫瘤標靶治療方面,運輸藥物到癌細胞內。

應用範圍

可應用於生物醫學相關市場,如診斷試劑開發、治療用抗體開發等領域。

接受技術者具備基礎建議(設備)

1.哺乳類細胞培養設備。 2.蛋白質純化設備。

接受技術者具備基礎建議(專業)

1.分子生物學。 2.哺乳類細胞培養技術。 3.蛋白質純化技術。

技術分類 生物工程

聯絡資訊

聯絡人:楊明華 標靶藥物技術中心

電話:+886-3-5914932 或 Email:minghua@itri.org.tw

客服專線:+886-800-45-8899

傳真:+886-3-5910097

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