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Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms
Nature Biotechnology ( IF 46.9 ) Pub Date : 2024-05-07 , DOI: 10.1038/s41587-024-02232-0
Rémy Pétremand , Johanna Chiffelle , Sara Bobisse , Marta A. S. Perez , Julien Schmidt , Marion Arnaud , David Barras , Maria Lozano-Rabella , Raphael Genolet , Christophe Sauvage , Damien Saugy , Alexandra Michel , Anne-Laure Huguenin-Bergenat , Charlotte Capt , Jonathan S. Moore , Claudio De Vito , S. Intidhar Labidi-Galy , Lana E. Kandalaft , Denarda Dangaj Laniti , Michal Bassani-Sternberg , Giacomo Oliveira , Catherine J. Wu , George Coukos , Vincent Zoete , Alexandre Harari

A central challenge in developing personalized cancer cell immunotherapy is the identification of tumor-reactive T cell receptors (TCRs). By exploiting the distinct transcriptomic profile of tumor-reactive T cells relative to bystander cells, we build and benchmark TRTpred, an antigen-agnostic in silico predictor of tumor-reactive TCRs. We integrate TRTpred with an avidity predictor to derive a combinatorial algorithm of clinically relevant TCRs for personalized T cell therapy and benchmark it in patient-derived xenografts.



中文翻译:

使用组合算法识别临床相关 T 细胞受体以进行个性化 T 细胞治疗

开发个性化癌细胞免疫疗法的一个核心挑战是肿瘤反应性 T 细胞受体 (TCR) 的识别。通过利用肿瘤反应性 T 细胞相对于旁观者细胞的独特转录组学特征,我们构建并基准化了 TRTpred,这是一种肿瘤反应性 TCR 的计算机模拟预测因子,与抗原无关。我们将 TRTpred 与亲和力预测器相结合,得出用于个性化 T 细胞治疗的临床相关 TCR 的组合算法,并在患者来源的异种移植物中对其进行基准测试。

更新日期:2024-05-07
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