化学的に定義された抗体と小分子薬の結合体における腫瘍標的化:比較分析

Samuele Cazzamalli¹, Alberto Dal Corso¹, Fontaine Widmayer¹

¹Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH Zürich) , Vladimir-Prelog-Weg 4, CH-8093 Zurich, Switzerland.

Journal of the American Chemical Society

|January 18, 2018

まとめ

この研究では,抗体-薬剤併用剤と小分子-薬剤併用剤をがん治療に比較しています. 腫瘍低酸素症と腎臓細胞癌のマーカーである炭酸アンヒドラゼIXを標的とする薬剤です.

科学分野:

腫瘍学
薬理学について
生物化学

背景:

炭酸水素 IX (CA IX) は腫瘍低酸素症の有効なバイオマーカーである.
CA IXは,クリアセル腎臓がん (ccRCC) で高度に発現する.
有効ながん治療には標的型療法が不可欠です

研究の目的:

抗体-薬物結合体 (ADC) と小分子-薬物結合体 (SMDC) の有効性を直接比較する.
炭酸アンヒドラゼIX (CA IX) を標的とするこれらの結合体を評価する.
特に腎臓細胞がんの治療薬としての可能性を評価する.

主な方法:

CA IXを標的とした化学的に定義されたADCとSMDCの開発.
インビトロとインビボの比較研究
結合親和性と治療効果の評価

主要な成果:

ADCとSMDCの両方がCA IXに高親和性結合を示した.
ADCとSMDCの治療効果を比較したデータを作成した.
この研究は,これらの2つの結合型の直接的な評価を提供します.

結論:

抗体-薬剤結合体と小分子-薬剤結合体は,CA IXを標的とした有効な治療戦略を表しています.
この比較評価は新しい標的型がん治療法の開発に役立つ.
腎臓細胞癌および他のCA IX発現腫瘍における臨床適用のためにこれらの結合体を最適化するためにさらなる研究が必要である.

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