Engineering Dual-Targeted CD19/BCMA CAR-T Cells for the Treatment of Multiple Sclerosis in a Preclinical Model
Andre Tran
Department of Biology
Faculty Supervisor: Lily Chen
Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy with potential to treat multiple sclerosis (MS). In MS, autoreactive B cells drive inflammation and disease progression, and current B-cell–depleting therapies do not fully eliminate pathogenic populations within the central nervous system (CNS). Anti-CD19 CAR T cells can traffic to the CNS and deplete a broad range of B cells, but may spare late-stage populations. In contrast, B-cell maturation antigen (BCMA) is expressed on late-stage B cells, including plasma cells, that continue producing pathogenic antibodies. Moreover, recombinant human myelin oligodendrocyte glycoprotein (rhMOG)-induced experimental autoimmune encephalomyelitis (EAE), a B-cell–dependent model of MS, anti-CD19 CAR T cells have previously been shown to improve disease, supporting the therapeutic potential of B-cell–targeted approaches. We hypothesize that dual targeting of CD19 and BCMA will enhance clearance of late-stage B-cell populations and result in more durable B-cell depletion compared with CD19-targeted CAR T cells alone. This approach may represent a promising therapeutic strategy and supports further evaluation of dual-targeted CAR T-cell therapies.