Identification of clinically relevant T cell receptors for personalized T cell therapy using combinatorial algorithms.

Pétremand, Rémy; Chiffelle, Johanna; Bobisse, Sara; Perez, Marta A S; Schmidt, Julien; Arnaud, Marion; Barras, David; Lozano-Rabella, Maria et al. · Nat Biotechnol · 2025

basic_science · Level V

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Abstract

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.

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