Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy
The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2025
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| In: |
Nature biotechnology
Year: 2025, Jahrgang: 43, Heft: 1, Pages: 134-142 |
| ISSN: | 1546-1696 |
| DOI: | 10.1038/s41587-024-02161-y |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41587-024-02161-y Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41587-024-02161-y |
| Verfasserangaben: | C.L. Tan, K. Lindner, T. Boschert, Z. Meng, A. Rodriguez Ehrenfried, A. De Roia, G. Haltenhof, A. Faenza, F. Imperatore, L. Bunse, J.M. Lindner, R.P. Harbottle, M. Ratliff, R. Offringa, I. Poschke, M. Platten & E.W. Green |
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| 245 | 1 | 0 | |a Prediction of tumor-reactive T cell receptors from scRNA-seq data for personalized T cell therapy |c C.L. Tan, K. Lindner, T. Boschert, Z. Meng, A. Rodriguez Ehrenfried, A. De Roia, G. Haltenhof, A. Faenza, F. Imperatore, L. Bunse, J.M. Lindner, R.P. Harbottle, M. Ratliff, R. Offringa, I. Poschke, M. Platten & E.W. Green |
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| 520 | |a The identification of patient-derived, tumor-reactive T cell receptors (TCRs) as a basis for personalized transgenic T cell therapies remains a time- and cost-intensive endeavor. Current approaches to identify tumor-reactive TCRs analyze tumor mutations to predict T cell activating (neo)antigens and use these to either enrich tumor infiltrating lymphocyte (TIL) cultures or validate individual TCRs for transgenic autologous therapies. Here we combined high-throughput TCR cloning and reactivity validation to train predicTCR, a machine learning classifier that identifies individual tumor-reactive TILs in an antigen-agnostic manner based on single-TIL RNA sequencing. PredicTCR identifies tumor-reactive TCRs in TILs from diverse cancers better than previous gene set enrichment-based approaches, increasing specificity and sensitivity (geometric mean) from 0.38 to 0.74. By predicting tumor-reactive TCRs in a matter of days, TCR clonotypes can be prioritized to accelerate the manufacture of personalized T cell therapies. | ||
| 650 | 4 | |a Tumour immunology | |
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