The Potential Role of CAR-T Cell Therapy in Multiple Sclerosis

A satellite symposium titled ‘CAR T Therapy: The NEX-T Frontier in MS’ was held at the 40th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS). The symposium discussed current unmet needs and future advances in the management of multiple sclerosis (MS). Underlying the symposium was the importance of early intervention with disease-modifying therapy (DMT) in people with MS. As revealed by evidence from clinical trials and real-world studies, the layering of relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA) dictates how an individual with MS may develop disability as it accumulates through different mechanistic pathways over their disease course. Considering the ‘next frontier’ in MS, the critical role of B cells in chronic CNS inflammation was described. While anti-CD20 therapies have proven efficacy for relapsing forms of MS, they have failed to prevent long-term disability in progressive MS and their chronic use is associated with increased infection risk. High doses may have greater penetrance/benefit, but a high cumulative dose of anti-CD20 therapy may be associated with increased safety concerns. CD19 or B cell maturation antigen (BCMA) CAR-T cell therapy can cross the blood–brain barrier and may allow for a deep but non-sustained B cell depletion with immune reset. Efficacy and safety results available thus far support further investigation of CAR-T cell treatments in controlled clinical trials in people with MS.