Bicistronic-CD19/22 Chimeric Antigen Receptor T-Cell Therapy for Childhood Refractory Lupus Nephritis.

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disease and approximately 40% of patients with SLE progress to lupus nephritis (LN). The treatment of refractory SLE and LN remains challenging. This clinical study aimed to evaluate the efficacy and safety of bicistronic-CD19/22 targeted chimeric antigen receptor T-cell (CAR-T) therapy in pediatric patients with refractory LN. Methods: Three pediatric patients (aged 14-17 years) with refractory class IV ± III/V LN were enrolled in the study. These patients had previously failed multiple immunosuppressive therapies. Following lymphodepleting chemotherapy with fludarabine and cyclophosphamide, patients underwent autologous bicistronic-CD19/22 CAR-T therapy. Clinical responses were analyzed. Results: All patients achieved significant clinical remission within 3 months. During the 9- to 15-month follow-up period, all patients were maintained drug-free SLE or LN remission. Two patients developed grade 1 cytokine release syndrome (CRS). Another patient experienced grade 4 CRS complicated by hemophagocytic lymphohistiocytosis (HLH) and thrombotic microangiopathy (TMA), which was controlled with combination therapy of methylprednisolone, etoposide, and eculizumab. Deep B-cell depletion was achieved within 1 week following CAR-T infusion. The mean time to peripheral B-cell reconstitution was 89 ± 32 days, with the reconstituted B-cell population predominantly composed of CD27-negative naïve B cells, only minimal numbers of memory B cells and CD38+CD20- plasmablasts. Conclusion: Bicistronic-CD19/22 CAR-T therapy has induced sustained remission in pediatric patients with refractory LN. Although the treatment triggered severe complications-HLH/TMA. These complications were manageable with aggressive supportive therapy, underscoring the importance of meticulous patient screening before CAR-T administration. This therapy offers a promising treatment strategy for refractory LN.