Computational identification of cross-reactive TCR epitopes with ARDitox.

ABSTRACT:

Background

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.

Methods

To address this issue, we developed ARDitox, a novel in silico method based on computational immunology and artificial intelligence (AI) for predicting and analyzing potential TCR off-target toxic

SUBMITTER: Murcia Pienkowski V 

PROVIDER: S-EPMC12579651 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature