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Computational identification of cross-reactive TCR epitopes with ARDitox

Cellular immunotherapies, such as those utilizing T lymphocytes expressing native or engineered T cell receptors (TCRs), have demonstrated therapeutic efficacy. However, some engineered high-affinity TCRs have caused fatal off-target immunotoxicity due to targeting epitopes later found to be express...

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Main Authors: Murcia Pienkowski, Victor (Author) , Boschert, Tamara (Author) , Skoczylas, Piotr (Author) , Sanecka-Duin, Anna (Author) , Jasiński, Maciej (Author) , Król-Józaga, Bartłomiej (Author) , Mazzocco, Giovanni (Author) , Stachura, Sławomir (Author) , Bunse, Lukas (Author) , Kaczmarczyk, Jan (Author) , Green, Edward W. (Author) , Blum, Agnieszka (Author)
Format: Article (Journal)
Language:English
Published: 01 November 2025
In: Journal of cancer research and clinical oncology
Year: 2025, Volume: 151, Issue: 12, Pages: 1-15
ISSN:1432-1335
DOI:10.1007/s00432-025-06330-7
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1007/s00432-025-06330-7
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Author Notes:Victor Murcia Pienkowski, Tamara Boschert, Piotr Skoczylas, Anna Sanecka-Duin, Maciej Jasiński, Bartłomiej Król-Józaga, Giovanni Mazzocco, Sławomir Stachura, Lukas Bunse, Jan Kaczmarczyk, Edward W. Green, Agnieszka Blum
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Summary:Cellular immunotherapies, such as those utilizing T lymphocytes expressing native or engineered T cell receptors (TCRs), have demonstrated therapeutic efficacy. However, some engineered high-affinity TCRs have caused fatal off-target immunotoxicity due to targeting epitopes later found to be expressed by both tumor cells and healthy tissues. Unfortunately, TCRs can be cross-reactive to epitopes with highly distinct sequences, making prediction difficult, and the exquisite sequence specificity of TCRs means that safety studies in mice miss human-specific epitopes.
Item Description:Gesehen am 09.12.2025
Physical Description:Online Resource
ISSN:1432-1335
DOI:10.1007/s00432-025-06330-7

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