A new analysis of Kite’s Yescarta (axi-cel) trial data linked patient genetics to toxicity risk in CAR-T therapy. Researchers reporting in Science Immunology found that mutations in STXBP2 correlated with toxicity in six Zuma-1 participants, pointing to a potential biological marker for cytokine-release syndrome–like hyperinflammation. The work, led by Mark Leick at Massachusetts General Hospital and originating from studies with Marcela Maus’s lab, also highlighted a gene signal tied to CAR-T replication capability in vivo, which the team is now pursuing to improve engineering strategies. By using Zuma-1 and Zuma-7 datasets as comparison cohorts, the authors suggested the association may depend on baseline disease severity, adding nuance to how risk biology might translate across trial populations.