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恒常領域融合アーキテクチャを持つ工学双機能抗体
Juanjuan Du1,2, Yu Cao2, Yan Liu1
1California Institute for Biomedical Research , 11119 N. Torrey Pines Road, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|November 30, 2017
まとめ
研究者らは,抗体構造にタンパク質を挿入することで,二機能抗体を生成する新しい方法を開発しました. このアプローチにより,がん治療における有意な治療的可能性を持つ強力な Her2 × CD3 バイスペシフィック抗体が得られます.
科学分野:
- 免疫学
- バイオテクノロジー
- タンパク質工学
背景:
- 標的治療の開発には 抗体工学が不可欠です
- 多機能抗体を作るための現在の方法は,限界に直面しています.
- 多様な治療用途のための多機能な抗体プラットフォームが必要である.
研究 の 目的:
- タンパク質移植でバイ機能抗体を生成する新しい方法を開発する.
- エンジニアリングされた抗体の in vitro および in vivo の有効性を特徴づける.
- Her2 × CD3 バイスペシフィック抗体の治療的可能性を実証する.
主な方法:
- 全長タンパク質を抗体または抗原結合断片 (Fabs) の定常領域ループに移植する.
- アンチ-CD3 Fab にアンチ-Her2 単鎖変量断片 (ScFv) を挿入することによって Her2 × CD3 二固体抗体 (BsAb) を生成する.
- 細胞の活性,生理化学的特性,安定性を in vitro で評価する.
- マウスの異種移植モデルにおける in vivo 抗腫瘍活性評価
主要な成果:
- エンジニアリングされた二機能抗体は,優れた in vitro 活性,安定性,および生理化学的特性を示す.
- Her2 × CD3 BsAbは,ピコモラ以下濃度で効率的な標的細胞解離を示した.
- Her2 × CD3 BsAbは, Her2 を発現する異種移植モデルにおいて, in vivoで強力な抗腫瘍効果を示した.
- タンパク質挿入法により 多機能抗体が作られました
結論:
- 抗体定常領域ループへのタンパク質移植は,二機能抗体を生成するための実行可能な戦略です.
- 合成された多機能抗体は,がん治療において重要な治療的可能性を秘めています.
- このアプローチは,新しい抗体ベースの治療法の開発に多岐にわたるプラットフォームを提供します.
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