We are pleased to share our latest collaborative publication with researchers from the German Cancer Research Center (DKFZ) and Heidelberg University, titled “Computational identification of cross-reactive TCR epitopes with ARDitox.”
The study explores how AI-driven in silico methods can support the safety assessment of
T cell receptor (TCR)-based immunotherapies. Using ARDitox, our platform for predicting potential TCR off-target toxicities, the team analyzed several clinically relevant TCRs, including those known to cause adverse immunotoxic effects, and successfully identified previously confirmed cross-reactive epitopes.
The approach was also applied to a novel TCR targeting the tumor-associated antigen NLGN4X, frequently upregulated in gliomas, where ARDitox revealed a potential cross-reactive human peptide that would not have been detected in traditional animal models.
This work highlights the value of computational immunology in improving the safety of next-generation cellular therapies and demonstrates the impact of collaboration between industry and leading academic research centers.
This is not the first publication where ARDitox has proven its capabilities. While this study focuses on the methodology itself, a previous paper published earlier this year in Nature Communications showcased a successful application of ARDitox in a different therapeutic context: https://ardigen.com/advancing-tcr-t-therapy-for-glioblastoma/
ARDiTox was used to de-risk the vaccine-induced TCR therapy by predicting potential off-target peptide/MHC ligands and scoring their safety and presentation likelihood. These in-silico hits were then prioritized for experimental testing.
We would like to congratulate all co-authors on this achievement and thank everyone involved for their valuable contributions.
Victor Murcia Pienkowski1, Tamara Boschert2,3, Piotr Skoczylas1, Anna Sanecka-Duin1, Maciej Jasiński1, Bartłomiej Król-Józaga1, Giovanni Mazzocco1, Sławomir Stachura1, Lukas Bunse2,3,4,5, Jan Kaczmarczyk1, Edward W. Green2,3,4*, Agnieszka Blum1*
Affiliations:
- Ardigen S.A., AI Lab, Krakow, Poland
- Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- German Cancer Consortium (DKTK), DKFZ, core center Heidelberg, Heidelberg, Germany.
- DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.
- Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translation Neuroscience (MCTN), Heidelberg University, Mannheim, Germany.
* Authors contributed equally
