SCAR02 CAR-T cells targeting CD19 and BCMA induce drug-free remission in refractory SLE patients

For patients with Systemic Lupus Erythematosus (SLE), particularly those with refractory disease, current immunosuppressive therapies often fail to achieve sustained remission, leading to cumulative organ damage and reduced quality of life. B cells play a central role in SLE pathogenesis by producing autoantibodies and acting as antigen-presenting cells. While B-cell depletion therapies exist, they may not be sufficient for severe, refractory cases. Chimeric Antigen Receptor T-cell (CAR-T) therapy, which genetically engineers T cells to target specific B-cell markers like CD19 and BCMA, offers a potent strategy for deep and sustained B-cell depletion, potentially resetting immune tolerance in these challenging patients.

This prospective case series enrolled 3 female patients (aged 25, 37, 41 years) with refractory systemic lupus erythematosus (rSLE). Following lymphodepleting preconditioning with cyclophosphamide and fludarabine, patients received a single infusion of 4th-generation SCAR02 CAR-T cells. Two patients received a low dose (0.5×10⁶/kg) and one patient received a medium dose (1.0×10⁶/kg). SCAR02 CAR-T cells target both CD19 and BCMA and are engineered to secrete anti-IL-6 antibodies. Patients were followed for 12 months to assess safety (treatment-related adverse events, cytokines, immunoglobulin levels) and efficacy (cellular kinetics, clinical efficacy, serological markers like anti-double-stranded DNA antibodies and complement levels).

All 3 patients exhibited good CAR-T cell expansion, with no occurrence of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or other serious adverse events. Peripheral blood CD19⁺ B cells were completely depleted in all patients by days 9-13 post-infusion, with gradual recovery observed over 3-5 months. By month 12, significant clinical improvements were noted:

The SLE Disease Activity Index 2000 (SLEDAI-2K) scores decreased from baseline values of 8, 8, and 9 to 0, 4, and 0, respectively, for patients 1, 2, and 3. Anti-double-stranded DNA antibodies all turned negative, and complement levels returned to normal ranges. Based on the Definitions of Remission in SLE (DORIS) criteria, two patients achieved drug-free complete remission. The remaining one patient achieved an SLE Responder Index-4 (SRI-4) response, indicating a significant clinical improvement. The secretion of anti-IL-6 antibodies by SCAR02 cells is hypothesized to have contributed to the favorable safety profile.