CAR-T Cell-Mediated B Cell Depletion in Central Nervous System Autoimmunity

Objective Evaluate chimeric antigen receptor (CAR)-T cell mediated B depletion in experimental autoimmune encephalomyelitis (EAE). Background CAR-T cells are autologous T expressing a non-MHC target specific receptor. We tested whether anti-CD19 cells, which more thoroughly deplete human populations than monoclonal antibodies (mAbs), recapitulated the beneficial effects of EAE. Design/Methods Anti-CD19 or control that overexpressed green fluorescent protein were transferred into female wild-type C57BL/6 mice had been pretreated with cyclophosphamide. EAE was induced by immunization either recombinant (rh) myelin oligodendrocyte (MOG) (B cell-dependent) MOG peptide (p) 35-55 cell-independent). Mice evaluated daily for clinical signs and weekly peripheral counts. levels, immune modulation histology assessed at peak disease termination. Results In rhMOG-induced EAE, scores histologic lymphocyte infiltration reduced treated cyclophosphamide cells. observed lymphoid tissue central nervous system (CNS) CAR similar to anti-CD20 mAbs. There no difference including Th1 Th17 populations, but there trend towards increase Treg periphery CNS animals. Clinical did not differ among treatment groups p35-55-induced disease. Conclusions peripherally within CNS. Treatment also results less severe disease, it independent depletion. Our consistent data indicating across compartments, suggesting they may hold promise progressive MS.