耐火性がん患者のCRISPR技術によるT細胞

Edward A Stadtmauer^1,2, Joseph A Fraietta^2,3,4,5,6, Megan M Davis^5,6

¹Division of Hematology-Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. edward.stadtmauer@pennmedicine.upenn.edu cjune@upenn.edu.

Science (New York, N.Y.)

|February 8, 2020

まとめ

CRISPR-Cas9の遺伝子編集により T細胞ががんと闘うように設計されましたこのアプローチは安全性と実用性を示し,改変したT細胞は耐性がんの患者で最大9ヶ月持続しました.

科学分野:

免疫学
遺伝学
腫瘍学

背景:

CRISPR-Cas9遺伝子編集は T細胞媒介のがん免疫療法を強化する有望な戦略です
エンジニアリングT細胞はがん細胞を標的にし排除する能力を向上させることを目的としています

研究の目的:

癌治療のためのヒトT細胞におけるマルチプレックスCRISPR- Cas9遺伝子編集の安全性と実現可能性を評価する.
合成T細胞受容体 (TCR) を発現し,PD-1 を欠く人工T細胞の有効性を評価する.

主な方法:

3人の耐火性がん患者の臨床試験です
マルチプレックスCRISPR- Cas9編集は,内生的なTCR遺伝子 (TRAC,TRBC) とPDCD1を削除し,がん特有のTCRトランスゲン (NY- ESO- 1) を導入するために使用されました.
遺伝子組み換えT細胞の養子移植と移植,持続性,安全性の監視

主要な成果:

遺伝子組み換えT細胞の耐久的な移植は,対象となる3つのゲノムロケーションすべてで成功しました.
染色体の転位が検出されたが,その頻度は時間とともに減少した.
エンジニアリングされたT細胞は最大9ヶ月持続し,最小限の免疫性を示した.

結論:

マルチプレックスCRISPR-Cas9遺伝子編集は,がんの免疫療法のためのT細胞の設計のための実現可能なアプローチです.
改変したT細胞の持続は,耐久的な抗腫瘍反応の可能性を示唆する.
この研究は,CRISPRベースのがん治療のさらなる臨床開発のための基盤を提供します.

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