Fig. 1: Clinical safety and efficacy of CD19/aIL-6/aTNFα CAR T-cells in RA.

a Design of chimeric antigen receptor (CAR) construct and sequences of anti-IL-6 single chain variable fragments (scFv) and anti-TNFα scFv. b Schematic illustration of CAR T-cells depleting CD19 B cells and secreting scFv of immunoglobulins against IL-6 and TNFα (CD19/aIL-6/aTNFα CAR T-cells). c Body temperature, heart rate and respiratory rate taken at the same time of the day after treatment with CAR T-cells. d Numbers of circulating CD19+ B cells in the patients’ peripheral blood. e Effects of CAR T-cells on tender and swollen joint counts (TJC, SJC). f Physician global assessment of disease activity using visual analog scale (VAS). g Effects of erythrocyte sedimentation rates (ESR) and C-reactive protein (CRP) levels. Disease activity scores-28 (DAS28) based on ESR and CRP (h) and clinical disease activity index (CDAI) and simplified disease activity index (SDAI) (i). j Serum levels of rheumatoid factor (RF) and antibodies against cyclic citrullinated peptide (CCP) at baseline and during 6-month follow-up. k Representative images of ultrasound Power Doppler (PD) signal (arrowheads) in the knee joint before and 3 months after CAR T-cell therapy (patient 2). Scale bars, 1 cm. l Representative MRI scans showing improved synovitis (arrowheads) of the hands and metacarpophalangeal joint (MCP) at baseline and 3 months after CAR T-cell treatment (patient 2). Scale bars, 1 cm. m Effects of CAR T-cell therapy on serum levels of immunoglobulins G (IgG), A (IgA), and M (IgM). Dotted lines, cut-off values.