Metabolon's Platform Reveals CAR T-cell Neurotoxicity Pathways

Metabolon, Inc. announced that its metabolomics platform was used by researchers from Gilead Sciences===Kite Pharma, a Gilead Sciences company, for the most extensive metabolomic study ever conducted in CAR T-cell therapy. The study analyzed over 3,800 samples from patients treated with FDA-approved CAR T-cell therapies, axicabtagene ciloleucel and brexucabtagene autoleucel. Investigators uncovered metabolic pathways strongly associated with severe neurological events (NEs), a significant toxicity of CAR T-cell therapy. Key findings include elevated tryptophan breakdown, increased arginine pathway activity, and metabolic disruptions in cerebrospinal fluid, all linked to higher neurotoxicity risk. Metabolite-based scores outperformed traditional inflammatory markers in predicting neurotoxicity, and these metabolites also tracked with worse disease progression. This research provides new biomarkers and potential therapeutic targets to mitigate severe neurotoxicity, enhancing cell therapy design and clinical outcomes.