Researchers identified genetic red flags tied to toxicity risk in Yescarta (axi-cel) recipients, using patient data from Kite’s Zuma-1 and Zuma-7 clinical trials. The analysis, published in Science Immunology, highlighted syntaxin binding protein 2 (STXBP2) mutations in Zuma-1 patients, with all six mutation carriers experiencing toxicity after treatment. The work, led by Mark Leick at Massachusetts General Hospital with Marcela Maus’s lab, links patient inherited DNA features to CAR-T behavior—specifically drawing parallels between CAR-T toxicity and hemophagocytic lymphohistiocytosis (HLH) biology. Leick said the field has long suspected variability in toxicity across patients, but that the study aimed to isolate additional factors beyond tumor traits. The results suggest a path for engineering next-generation CAR-Ts and for refining patient selection or monitoring strategies by incorporating toxicity-associated genomic signatures.