Immuno-engineering and Cellular Therapies
Sasha Gupta, MD
University of California, San Fransisco
San Francisco, California, United States
Milos Simic, PhD
University of California, San Fransisco
San Francisco, California, United States
Sharon Sagan, BS
University of California San Francisco
San Francisco, California, United States
Jason Duecker, BS
University of California San Francisco
San Francisco, California, United States
Chanelle Shepherd, BS
University of California San Francisco
San Francisco, California, United States
Stephen L. Hauser, n/a
University of California, San Francisco
San Francisco, California, United States
Wendell Lim, PhD
University of California San Francisco
San Francisco, California, United States
Michael R. Wilson, MD
Associate Professor, Neurology
University of California San Francisco
San Francisco, California, United States
Scott S. Zamvil, MD, PhD
University of California San Francisco
San Fransisco, California, United States
Chimeric antigen receptor (CAR)-T cells are T cells expressing non-MHC antigen specific receptor. We tested whether antiCD19 CAR-T cells could recapitulate the beneficial effects of B cell depletion in experimental autoimmune encephalomyelitis (EAE) mouse models.
Female wild-type C57BL/6 mice were treated with cyclophosphamide (preconditioning for CAR-T treatment) and anti-CD19 CAR-T cells or activated control T cells. EAE was induced by immunization with recombinant human (rh) myelin oligodendrocyte protein (MOG) (B cell-dependent) or MOG peptide (p) 35-55. Mice were evaluated daily for clinical signs of EAE and weekly for peripheral B/T cell counts. B cell levels, T cell immune modulation, and histopathology were assessed at termination.
In rhMOG-induced EAE, clinical scores were reduced in mice treated with cyclophosphamide and anti-CD19 CAR-T cells or control T cells in comparison to WT or cyclophosphamide alone treated mice. B cell depletion occurred only in the anti-CD19 CAR-T cell treated group, including within brain/spinal cord. There was no difference in T cell modulation including Th1, Th17, or Treg populations. Clinical scores did not differ between treatment groups in p35-55-induced disease. Histopathology is pending.
T cell therapy (CAR-T and control) resulted in less severe disease in B cell dependent EAE, but its effect was independent of B cell depletion or endogenous T cell. The mechanism for this observation has not been explained. The capability of anti-CD19 CAR-T cells to penetrate the CNS and more thoroughly deplete B cells than monoclonal antibodies suggest they may hold promise for depletion of CNS B cells implicated in progressive MS.
