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

Mackensen A, Müller F, Mougiakakos D, Böltz S, Wilhelm A, Aigner M, Völkl S, Simon D, Kleyer A, Munoz LE, Kretschmann S, Kharboutli S, Gary R, Reimann H, Rösler W, Uderhardt S, Bang H, Herrmann M, Ekici AB, Büttner C, Habenicht KM, Winkler T, Krönke G, Schett G (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Nature Medicine Nature Publishing Group

DOI: 10.1038/s41591-022-02017-5

Abstract

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 × 106 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.

Authors with CRIS profile

Andreas Mackensen Lehrstuhl für Innere Medizin V Fabian Müller Department of Medicine 5 – Haematology and Oncology Dimitrios Mougiakakos Medizinische Fakultät Sebastian Böltz Department of Medicine 5 – Haematology and Oncology Artur Wilhelm Department of Medicine 3 – Rheumatology and Immunology Simon Völkl Department of Medicine 5 – Haematology and Oncology David Simon Department of Medicine 3 – Rheumatology and Immunology Arnd Kleyer Department of Medicine 3 – Rheumatology and Immunology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Soraya Kharboutli Medizinische Fakultät Hannah Reimann Department of Medicine 5 – Haematology and Oncology Wolf Rösler Department of Medicine 5 – Haematology and Oncology Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Arif Bülent Ekici Institute of Human Genetics Christian Büttner Lehrstuhl für Humangenetik Katharina Marie Habenicht Professur für Genetik Thomas Winkler Professur für Genetik Gerhard Krönke Professur für Translationale Immunologie Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

ORGENTEC Diagnostika GmbH DE Germany (DE)

How to cite

APA:

Mackensen, A., Müller, F., Mougiakakos, D., Böltz, S., Wilhelm, A., Aigner, M.,... Schett, G. (2022). Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nature Medicine. https://dx.doi.org/10.1038/s41591-022-02017-5

MLA:

Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022).

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