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Manufacturing Chimeric Antigen Receptor CAR T Cells for Adoptive Immunotherapy
Published on: December 17, 2019
CD19-Directed CAR T-Cells in a Patient With Refractory MOGAD: Clinical and Immunologic Follow-Up for 1 Year
Jose Maria Cabrera-Maqueda1, Maria Sepulveda1, Raquel Ruiz García1
1From the Neuroimmunology and Multiple Sclerosis Unit (J.M.C.-M., M.S., R.R.G., M.G., S.L., E.M.-H., T.A., E.G.F., M.T.A.-I., A.S., Y.B.), Service of Neurology, Hospital Clinic de Barcelona, and Universitat de Barcelona; Neuroimmunology Program (J.M.C.-M., M.S., R.R.G., M.G., S.L., E.M.-H., T.A., E.G.F., M.T.A.-I., J.D., A.S., Y.B.), Fundació de Recerca Clínic Barcelona- Institut d'Investigacions Biomèdiques August Pi i Sunyer; Department of Immunology (R.R.G., G.M.-S., D.L.-A., M.J.), Hospital Clínic de Barcelona, Fundació de Recerca Clínic Barcelona-Institut d'Investigacions Biomèdiques August Pi i Sunyer, Universitat de Barcelona; Department of Hematology (N.M.-C., V.O.-M., J.D.), Hospital Clínic de Barcelona; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS); Pediatric Neuroimmunology Unit (T.A.), Department of Neurology, Sant Joan de Déu (SJD) Children's Hospital, University of Barcelona; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) (J.D.); University of Barcelona; Caixa Research Institute (J.D.), Barcelona; and Joint Platform for Immunotherapy of Sant Joan de Deu - Hospital Clinic de Barcelona (M.J.), Spain.
Objectives:
In MOG antibody-associated disease (MOGAD), relapse prevention and the treatment approach to refractory symptoms are unknown. We report a patient with refractory MOGAD treated with CD19-directed CAR T-cells.
Methods:
CD19-directed CAR T-cells (ARI-0001) were produced in-house by lentiviral transduction of autologous fresh leukapheresis and infused after a conventional lymphodepleting regimen.
Results:
A 18-year-old man developed 2 episodes of myelitis associated with serum MOG-IgG, which were followed by 6 episodes of left optic neuritis (ON) and sustained the presence of MOG-IgG over 6 years despite multiple immunotherapies. After the sixth episode of ON, accompanied by severe residual visual deficits, CAR T-cell treatment was provided without complications. Follow-up of cell counts showed complete depletion of CD19+ B cells at day +7; reconstituted B cells at day +141 showing a naïve B-cell phenotype, and low or absent memory B cells and plasmablasts for 1 year. MOG-IgG titers have remained undetectable since CAR T-cell infusion. The patient had an early episode of left ON at day +29, when MOG-IgG was already negative, and since then he has remained free of relapses without immunotherapy for 1 year.
Discussion:
This clinical case shows that CD19-directed CAR T-cell therapy is well-tolerated and is a potential treatment for patients with refractory MOGAD.
Classification Of Evidence:
This provides Class IV evidence. It is a single observational study without controls.

