scientists took T-cells from the lupus patients and modified them so that, on re-infusion, they attacked the patients’ B cells. In lupus, B cells churn out autoantibodies, which instead of defending the body against invading pathogens, attack healthy tissues instead. The therapy in effect wiped out the patients’ aberrant B cells and dramatically improved their condition. The disease affected multiple organs in all five patients, but after the therapy severe symptoms including arthritis, fatigue, fibrosis of the heart valves, and lung inflammation all cleared up.
Blood tests on the patients showed that their B cells recovered about four months after the treatment, but they no longer produced aberrant antibodies and the patients remained disease-free. The authors speculate that the therapy led to a “rebooting of the immune system.”
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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. 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.
— Read on www.nature.com/articles/s41591-022-02017-5