[Efficacy and safety of fourth-generation CAR-T cells targeting CD19 and BCMA with anti-IL-6 antibody secretion in refractory systemic lupus erythematosus].

Clinical data of 3 patients with refractory systemic lupus erythematosus (rSLE) who received chimeric antigen receptor T-cell (CAR-T) therapy at the Department of Rheumatology and Immunology, the First Affiliated Hospital of University of Science and Technology of China, from June to September 2024 was prospectively enrolled. After lymphodepleting preconditioning with cyclophosphamide combined with fludarabine, 2 patients received a low dose (0.5×10⁶/kg) and 1 patient received a medium dose (1.0×10⁶/kg) of a 4th-generation CAR-T cells (SCAR02) targeting cluster of differentiation 19 (CD19) and B-cell maturation antigen (BCMA) and secreting interleukin-6 (IL-6) antibodies. Follow-up was conducted at day 14 and months 1, 2, 3, 6, 9, and 12 post-infusion to systematically evaluate safety (including treatment-related adverse events, cytokines, and immunoglobulin levels) and efficacy (including cellular kinetics, clinical efficacy, and serological markers). All 3 patients were females, aged 37, 25, and 41 years, respectively. During the follow-up period, no cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or other serious adverse events occurred. CAR-T cells expanded well in all patients; peripheral blood CD19⁺ B cells were completely depleted on days 9-13 and gradually recovered over 3-5 months. By month 12, the SLE Disease Activity Index 2000 (SLEDAI-2K) scores of patients 1 to 3 decreased from 8, 8, and 9 at baseline to 0, 4, and 0, respectively; anti-double-stranded DNA antibodies all turned negative, and complement levels returned to normal. Two patients achieved drug-free complete remission based on the Definitions of Remission in SLE (DORIS) criteria, and 1 patient achieved an SLE Responder Index-4 (SRI-4) response. This study demonstrates that SCAR02 exhibits a good safety profile and preliminary efficacy in rSLE patients, and its function of secreting IL-6 antibodies may help alleviate CRS.