ヘルセプチン抗体の変種は,抗原結合部位でHER2とVEGFと相互作用する
Jenny Bostrom1, Shang-Fan Yu, David Kan
1Department of Protein Engineering, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
まとめ
研究者らは,ヒトの表皮成長因子受容体2 (HER2) と血管内皮成長因子 (VEGF) となる2つの異なるタンパク質に結合できる新しい抗体を設計した. この"two-in-one"抗体は,新たな治療戦略の有望性を示しています.
科学分野:
- 免疫学 免疫学とは
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- 抗体と抗原の相互作用は,通常,一つの抗体が単一の抗原に結合するロック&キーモデルに従って特異的です.
- モノクローナル抗体は高度に特異的な治療薬であり,ヒトの表皮成長因子受容体2 (HER2) を標的にするハーセプチンはその例です.
研究 の 目的:
- 2つの異なる抗原を同時に結合する能力を有する抗体を設計し,特徴づけること.
- 二重抗原結合の構造的基礎とその治療的可能性を調査する.
主な方法:
- 二重結合能力を持つハーセプチン変異体の分離.
- 結晶学と変異性研究により,結合界面を明らかにする.
- マウスにおける細胞増殖アッセイ in vitroおよび腫瘍進行モデル in vivo.
主要な成果:
- 新しい抗体であるbH1が開発され,HER2と血管内皮成長因子 (VEGF) の両方を高親和性で結合する.
- 構造分析により,各抗原に結合する異なったアミノ酸残基が検出され,抗体の結合表面が著しく重なり合っていた.
- 強化されたbH1変種は,前臨床モデルにおいて,HER2およびVEGF駆動の細胞増殖と腫瘍増殖の両方を効果的に抑制した.
結論:
- この研究は,
- ツー・イン・ワンです.
- 伝統的なモノクローナル抗体パラダイムに挑戦する抗体.
- この二重標的抗体プラットフォームは,複数のシグナル伝達経路を含む疾患に対する新しい治療の機会を提供します.
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