Cell Res：我国学者首次使用现货通用型CAR-T疗法成功治疗系统性红斑狼疮

Core Viewpoint - The study demonstrates the safety and efficacy of allogeneic CD19-targeted CAR-T cell therapy (TyU19) in treating refractory systemic lupus erythematosus (SLE), marking a significant advancement in the application of CAR-T cell therapy for autoimmune diseases [2][3][16]. Group 1: Research Background - In 2021, researchers at Erlangen-Nuremberg University successfully treated a patient with refractory SLE using CAR-T cell therapy, leading to numerous clinical trials worldwide to evaluate its safety and efficacy in B cell-mediated autoimmune diseases [2]. - Allogeneic CAR-T cells offer advantages such as uniformity, rapid availability, and potential cost-effectiveness, but face limitations due to risks like graft-versus-host disease (GvHD) and gene editing-related toxicity [2][3]. Group 2: Study Details - The study, a single-center pilot trial (NCT05988216), assessed the safety and efficacy of TyU19 in patients with refractory SLE, utilizing CRISPR-Cas9 gene editing to modify CAR-T cells from healthy donors [6][12]. - Four young female patients aged 22-24 with a history of multiple organ involvement were included, all having baseline SELENA-SLEDAI scores between 14-26 [7]. Group 3: Treatment Protocol and Results - Patients underwent a lymphocyte-depleting chemotherapy regimen before receiving a dose of 1×10^6 CAR-T cells/kg [7]. - All patients showed sustained clinical improvement, achieving a SELENA-SLEDAI score of zero and a PGA score of less than 1 within 3-6 months post-treatment [9][11]. - Symptoms such as arthritis, hair loss, and finger vasculitis resolved, and levels of complement factors C3 and C4 normalized [9]. Group 4: Safety Profile - The most common grade 3 or 4 adverse events included neutropenia, lymphopenia, and liver dysfunction, attributed to the lymphocyte-depleting pre-treatment [11]. - No patients experienced severe adverse events like immune effector cell-associated neurotoxicity syndrome (ICANS) or GvHD, and no infections occurred during the study [11][12]. Group 5: Innovative Aspects - TyU19 demonstrated a significant innovation by requiring a less intensive lymphocyte-depleting regimen compared to traditional CAR-T therapies, even exploring a "no depletion" approach [12]. - The therapy showed potential for long-term efficacy by targeting both abnormal B cells and inhibiting plasma cell regeneration, as evidenced by the reduction of BCMA+ and CD19-BCMA+ plasma cells post-treatment [15][16]. Group 6: Conclusion and Future Directions - The study highlights the potential of allogeneic CD19-targeted CAR-T cell therapy as a promising treatment for refractory SLE, warranting further research to explore its long-term efficacy and optimize its application in challenging autoimmune diseases [16].