Clinicians at the University of Nebraska’s Fred & Pamela Buffett Cancer Center administered a pioneering allogeneic CAR T-cell therapy, azercabtagene zapreleucel (azer-cel), to a 49-year-old patient with progressive multiple sclerosis (MS). This off-the-shelf CD19-directed therapy aims to eliminate aberrant B cells implicated in the neurodegenerative autoimmune condition. The intervention, conducted in a Phase I clinical trial sponsored by TG Therapeutics, represents a world first and holds promise for addressing the significant unmet medical need in progressive MS forms poorly responsive to existing disease-modifying therapies. Trial leads Professor Rana Zabad and Professor Matthew Lunning highlighted the therapeutic potential to cross the blood-brain barrier and modify disease activity. With an estimated 2.9 million people affected worldwide, progressive MS urgently necessitates innovative treatments that can prevent neurodegeneration and disability progression.