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

Nat Biotechnol. 2025 Mar;43(3):323-328. doi: 10.1038/s41587-024-02232-0. Epub 2024 May 7.

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.

MeSH terms

  • Algorithms*
  • Animals
  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive* / methods
  • Mice
  • Neoplasms* / immunology
  • Neoplasms* / therapy
  • Precision Medicine* / methods
  • Receptors, Antigen, T-Cell* / genetics
  • Receptors, Antigen, T-Cell* / immunology
  • T-Lymphocytes* / immunology

Substances

  • Receptors, Antigen, T-Cell