Over the course of several decades, NCI scientists laid extensive groundwork for a novel treatment that would eventually go on to become axicabtagene ciloleucel (Yescarta), a CAR T-cell therapy for adults with lymphoma. While the therapy can lead to long-lasting remissions for some patients with very advanced cancer, it can also cause neurologic side effects such as speech problems, tremors, delirium, and seizures. Some side effects can be severe or fatal. So, in 2017, NCI researchers tweaked their original CAR T-cell design with the goal of creating a safer and more effective therapy. Now results from the first clinical trial of the remodeled CAR T cells suggest that they may have achieved part of their goal. The new therapy caused far fewer neurologic side effects than the original therapy did in an earlier trial, yet it was equally effective. The findings were reported January 20 in Nature Medicine. “It’s remarkable that out of 20 patients in this trial, only one had severe neurologic side effects,” said associate investigator Jennifer Brudno, M.D., of NCI’s Center for Cancer Research. “This appears to be a significant advance in our current understanding of how CAR T cells work and how to make a safer CAR T [-cell therapy],” said David Maloney, M.D., Ph.D., medical director of cellular immunotherapy for Fred Hutchinson Cancer Research Center, who was not involved in the study. However, the study is limited by the small number of patients involved and the relatively short amount of time patients’ outcomes have been tracked, he added.