The University of Nebraska’s Fred & Pamela Buffett Cancer Center pioneered the first administration of an allogeneic CD19-directed CAR T-cell therapy, azercabtagene zapreleucel (azer-cel), to a patient with progressive multiple sclerosis (MS). This off-the-shelf therapy targets CNS-resident immune cells implicated in MS neurodegeneration. Early reports from patient Jan Janisch-Hanzlik indicate improved gait and symptom relief. The Phase I trial aims to address treatment gaps in progressive MS forms, which currently lack effective disease-modifying therapies.