Journal Article

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus

Kharboutli, Soraya, Munoz, Luis, Herrmann, Martin, Völkl, Simon, Habenicht, Katharina Marie, Schett, Georg, Buettner, Christian, Winkler, Thomas H., Uderhardt, Stefan, Bang, Holger, Mougiakakos, Dimitrios, Kleyer, Arnd, Böltz, Sebastian, Wilhelm, Artur, Reimann, Hannah, Aigner, Michael, Rösler, Wolf, Ekici, Arif Bülent, Mackensen, Andreas, Simon, David, Kretschmann, Sascha, Müller, Fabian, Gary, Regina, Krönke, Gerhard

2022

Overview

Systemic lupus erythematosus (SLE) is a life-threatening autoimmune disease characterized by adaptive immune system activation, formation of double-stranded DNA autoantibodies and organ inflammation. Five patients with SLE (four women and one man) with a median (range) age of 22 (6) years, median (range) disease duration of 4 (8) years and active disease (median (range) SLE disease activity index Systemic Lupus Erythematosus Disease Activity Index: 16 (8)) refractory to several immunosuppressive drug treatments were enrolled in a compassionate-use chimeric antigen receptor (CAR) T cell program. Autologous T cells from patients with SLE were transduced with a lentiviral anti-CD19 CAR vector, expanded and reinfused at a dose of 1 × 10 6 CAR T cells per kg body weight into the patients after lymphodepletion with fludarabine and cyclophosphamide. CAR T cells expanded in vivo, led to deep depletion of B cells, improvement of clinical symptoms and normalization of laboratory parameters including seroconversion of anti-double-stranded DNA antibodies. Remission of SLE according to DORIS criteria was achieved in all five patients after 3 months and the median (range) Systemic Lupus Erythematosus Disease Activity Index score after 3 months was 0 (2). Drug-free remission was maintained during longer follow-up (median (range) of 8 (12) months after CAR T cell administration) and even after the reappearance of B cells, which was observed after a mean (±s.d.) of 110 ± 32 d after CAR T cell treatment. Reappearing B cells were naïve and showed non-class-switched B cell receptors. CAR T cell treatment was well tolerated with only mild cytokine-release syndrome. These data suggest that CD19 CAR T cell transfer is feasible, tolerable and highly effective in SLE. Results from a study of five patients with refractory systemic lupus erythematosus, who were treated with anti-CD19 CAR T cell therapy under a compassionate-use program, demonstrate remission of SLE disease with follow-up of up to 17 months.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 692/699/1670/1613 / 692/699/249/1313/1613 / Adaptive systems / Antibodies / Antigens / Antigens, CD19 / Autoantibodies / Autoimmune diseases / Biomedical and Life Sciences / Biomedicine / Body weight / Cancer Research / CD19 antigen / Cell therapy / Child / Chimeric antigen receptors / Chronic conditions / Cyclophosphamide / Cytokines / Deoxyribonucleic acid / Depletion / DNA / Dosage / Female / Fludarabine / Health services / Humans / Immune system / Immunosuppressive agents / Immunotherapy, Adoptive / Infectious Diseases / Lupus / Lupus Erythematosus, Systemic - drug therapy / Lymphocytes / Lymphocytes B / Lymphocytes T / Male / Metabolic Diseases / Molecular Medicine / Neurosciences / Patients / Receptors / Receptors, Antigen, B-Cell / Receptors, Chimeric Antigen - genetics / Remission / Remission (Medicine) / Seroconversion / Signs and symptoms / Systemic lupus erythematosus