A new analysis of patients treated with Kite Pharma’s CAR-T therapy Yescarta (axi-cel) has identified genetic signatures linked to toxicity risk, pointing to potential biomarkers and engineering targets for safer CAR-T designs. The results, published in Science Immunology, were led by Mark Leick, M.D., at Massachusetts General Hospital and conducted with Marcela Maus, M.D., Ph.D. Using data from the Zuma-1 and Zuma-7 trials, researchers reported that mutations in STXBP2 were present in six Zuma-1 patients and correlated with observed toxicity, while the association did not appear in the Zuma-7 cohort. The work ties CAR-T toxicity biology to pathways resembling hemophagocytic lymphohistiocytosis (HLH) and cytokine release syndrome. For CAR-T developers, the study adds a patient-genomics layer to toxicity risk stratification—potentially supporting both clinical monitoring approaches and next-generation CAR-T engineering strategies.