Taubmann Jule, Böltz Sebastian, Hagen Melanie, Wirsching Andreas, Müller Fabian, Völkl Simon, Kharboutli Soraya, Spörl Silvia, Garantziotis Panagiotis, Aigner Michael, Grieshaber-Bouyer Ricardo, Mackensen Andreas, Schett Georg
Medizinische Klinik 3 - Rheumatologie und Immunologie, Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, Ulmenweg 18, 91054, Erlangen, Deutschland.
Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg und Universitätsklinikum Erlangen, Erlangen, Deutschland.
Z Rheumatol. 2025 Sep 4. doi: 10.1007/s00393-025-01705-0.
Chimeric antigen receptor T-cells (CAR T-cells) are an effective therapeutic approach in the treatment of B-cell driven malignancies. In addition to malignant B-cells, autoreactive B-cells are important targets for CD19 CAR T-cells, as they are a source of autoantibody production and support both the onset and progression of systemic lupus erythematosus (SLE). We and others have shown that their use in severe and therapy-refractory cases of SLE is effective and, moreover, safe.
The current status and an interim analysis of the efficacy and safety of CD19-CAR T‑cell therapy in SLE.
Patients with severe, treatment-refractory, and active SLE received autologous CD19-CAR T‑cell therapy (MB19.1, Miltenyi Biotec, Bergisch Gladbach, Germany) as part of an individual compassionate treatment attempt and are regularly followed up at our center.
11 patients with progressive, therapy-refractory SLE received an autologous CD19 CAR T-cell therapy as part of an individual treatment attempt. The median follow-up time is 2.5 years [0.5 - 4 years]. All patients achieved a DORIS remission within 6 months. Immunosuppressive therapy was completely discontinued in all patients. Five out of the 11 patients experienced grade 1 cytokine release syndrome (CRS). Grade 2 CRS was observed only once. No higher-grade CRS occurred in this cohort. So far, no neurotoxicity (immune effector cell-associated neurotoxicity syndrome, ICANS) has been observed in our SLE patients. All patients remain in a sustained and drug-free remission to date. One patient experienced an SLE flare. Initial data, despite similar CD19 CAR T-cell expansion and kinetics, suggest a better safety profile of CD19 CAR T-cell therapy in SLE compared to lymphoma cohorts. Additionally, adaptive immunity in SLE patients recovers rapidly after CD19 CAR T-cell therapy.
The use of CD19-CAR T‑cells in patients with severe SLE proved to be safe and effective.
嵌合抗原受体T细胞（CAR T细胞）是治疗B细胞驱动的恶性肿瘤的一种有效治疗方法。除恶性B细胞外，自身反应性B细胞也是CD19 CAR T细胞的重要靶点，因为它们是自身抗体产生的来源，并且支持系统性红斑狼疮（SLE）的发病和进展。我们和其他人已经表明，将其用于SLE的重症和治疗难治性病例是有效且安全的。
CD19 CAR T细胞疗法治疗SLE的疗效和安全性的现状及中期分析。
患有重症、治疗难治性和活动性SLE的患者接受了自体CD19 CAR T细胞疗法（MB19.1，德国米尔滕yi生物技术公司，伯格isch格拉德巴赫），作为个体化同情治疗尝试的一部分，并在我们中心定期随访。
11例进行性、治疗难治性SLE患者接受了自体CD19 CAR T细胞疗法，作为个体化治疗尝试的一部分。中位随访时间为2.5年[0.5 - 4年]。所有患者在6个月内实现了DORIS缓解。所有患者均完全停用免疫抑制治疗。11例患者中有5例出现1级细胞因子释放综合征（CRS）。仅观察到1次2级CRS。该队列中未发生更高级别的CRS。到目前为止，我们的SLE患者中未观察到神经毒性（免疫效应细胞相关神经毒性综合征，ICANS）。所有患者至今仍处于持续无药缓解状态。1例患者出现SLE复发。尽管CD19 CAR T细胞扩增和动力学相似，但初步数据表明，与淋巴瘤队列相比，CD19 CAR T细胞疗法在SLE中的安全性更好。此外，SLE患者的适应性免疫在CD19 CAR T细胞疗法后迅速恢复。
在重症SLE患者中使用CD19 CAR T细胞被证明是安全有效的。
