PD-1チェックポイントブロックベースの免疫療法のための全腫瘍ゲノムバイオマーカー
Razvan Cristescu1, Robin Mogg2, Mark Ayers2
1Merck & Co., Kenilworth, NJ 07033, USA. razvan_cristescu@merck.com.
まとめ
腫瘍変異負荷 (TMB) とT細胞炎症性遺伝子発現プロファイル (GEP) は,ペンブロリズマブのようなPD-1免疫療法に対する反応を予測する. これらの独特のバイオマーカーは,免疫療法から恩恵を受ける可能性のある患者を特定し,臨床試験の設計を支援します.
科学分野:
- 免疫療法
- 腫瘍学
- ゲノミクス
背景:
- プログラム細胞死タンパク質-1 (PD-1) とプログラム細胞死リガンド-1 (PD- L1) のチェックポイント阻害免疫療法は,耐久的な抗腫瘍効果を提供します.
- しかし,すべてのがん患者がこの治療に反応するわけではありません.
研究 の 目的:
- ペンブロリズマブに対する腫瘍変異負荷 (TMB) とT細胞炎症遺伝子発現プロファイル (GEP) の予測的有用性を評価する.
- TMB と GEP の間の相関を調査し,応答者と非応答者を特定する.
主な方法:
- 4つのKEYNOTE臨床試験の22種類の腫瘍から300人の患者のサンプルを分析した.
- バイオマーカーの相関性に関する癌ゲノムアトラス (TCGA) データベースの評価.
- バイオマーカーで定義された耐性パターンを特定するための関節層化分析
主要な成果:
- TMBとT細胞炎症によるGEPは,PD- 1抗体ペムブロリズマブに対する反応を共同で予測した.
- TMBとGEPはそれぞれ独立して反応を予測した.
- TMBとGEPの相関は低いため 異なる生物学的特徴を捉えていることが示された.
結論:
- TMBとGEPはPD-1封鎖免疫療法に反応する患者を特定するための貴重なバイオマーカーです.
- これらのバイオマーカーは,適切な免疫療法 (単独療法または併用療法) を選択するための臨床試験の設計に情報を与えることができます.
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