多数の受容体をトランスクリプションでリンクすることで設計された正確なT細胞認識プログラム
Jasper Z Williams1,2,3, Greg M Allen1,2,3,4, Devan Shah1,2,3
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
Science (New York, N.Y.)
|November 27, 2020
まとめ
エンジニアリングされたT細胞は,合成のノッチ受容体を使って複数の抗原信号を統合することで,標的細胞を正確に認識します. この多受容体系は 選択的に腫瘍を標的にし 優れた細胞認識能力を発揮します
科学分野:
- 合成生物学
- セルラーエンジニアリング
- 免疫学
背景:
- 細胞認識は複数の受容体からの信号を 統合することで精度が向上します
- 個々の分子相互作用には 複雑な生物学的認識の作業に必要な精度が 欠けていることが多い.
- 合成生物学では 新しい細胞機能を設計するツールが提供されます
研究 の 目的:
- 合成のノッチ受容体を使って 多受容体細胞認識回路を設計する
- 合成T細胞が複数の抗原認識イベントを統合できるように
- 調節可能なロジックで 精密で頑丈なセルラー認識を実現します
主な方法:
- 合成ノッチ受容体のライブラリを設計し,トランスクリプションの相互接続を作成しました.
- 統合された細胞外および細胞内抗原認識経路
- 陽性と負の論理ゲートを導入した.
- 3つの抗原とゲート回路をテストした
主要な成果:
- 3つの異なる抗原を統合できる 合成回路を開発しました
- 細胞の異質性に対する強度を示した.
- エンジニアリングされたT細胞は 統合された抗原信号に基づいて 精密な認識を示しました
- 3つの抗原とゲートは選択的に3つの抗原の腫瘍を in vivoで除去し,2つの抗原の腫瘍を保存した.
結論:
- 合成ノッチ受容体ベースの回路は,複雑な,多受容体媒介の細胞間認識を可能にします.
- 細胞の行動を設計する強力な戦略です 細胞の行動を設計する強力な戦略です
- このアプローチは,特に癌の治療のために,エンジニアリングされた細胞療法における特異性と精度を高める.
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