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Background: Lately, autologus CD19-targeting chimeric antigen receptor (CAR) T cells have shown excellent efficacy in treatment of autoimmune diseases, but with great safety concerns, such as infections. In this study, we aimed to evaluate the safety, tolerability and efficacy of allogeneic CD19 CAR-NK cell therapy in patients with relapsed or refractory systemic lupus erythematosus (SLE).
Objectives: To evaluate the safety and efficacy of allogenic CD19-targeting CAR-nature killing (NK) cells in 18 patients with severe and refractory SLE.
Methods: In this open-label, single arm, prospective and first-in-human trial, we evaluated allogeneic CD19 CAR-NK cell therapy in adult patients with relapsed or refractory SLE. Patients who had received at least two previous standard systemic therapies and continued to exhibit moderate-to-severe disease activity were eligible for inclusion. This study consisted of schedule- and dose-escalation. All subjects received one 3 doses treatment cycle consisted of 3 doses after conditioning chemotherapy with fludarabine (25 mg/m²) and cyclophosphamide (300 mg/m²) intravenously on days –5 to –3. Dose-limiting adverse events were monitored in patients for 28 days. The primary endpoints of this study were safety and tolerability, including the incidence of dose-limiting toxicities and severe adverse events (SAE) according to National Cancer Institute Common Toxicity Criteria and Adverse Events version 5·0. The secondary endpoint was the efficacy assessed by Physician Global Assessment, SLEDAI-2000 score, definition of low disease activity state (LLDAS) and definition of remission in SLE (DORIS 2021). This trial was registered with ClinicalTrials.gov, NCT06010472.
Results: 26 relapsed or refractory SLE patients with moderate-to-severe disease activity were enrolled. Of the 24 patients, 22 (82%) were female; the median age was 38 years, and the median disease duration was 8.5 years. Patients had received at least two standard systemic therapies, including 18 (75%) of 24 patients treated with biological agents (Belimumab and Telitacicept), and 1 who underwent plasmapheresis. The maximum tolerated dose was not reached. Cytokine release syndrome (CRS) was reported in 2 (8%) (grade 1) of 18 patients, neurotoxicity and other CAR-NK therapy related severe adverse events were not observed. Of the 12 patients with more than 12 months follow-up, 66.7 % (8/12) achieved DORIS remission and 75 % (9/12) achieved LLDAS.
Conclusion: This study supports that Allogeneic CAR-NK cell therapy is a potent option for autoimmune diseases treatment and indicates that such a therapy might address limitations of currently autologous CAR-T cell therapy, including manufacturing scale and time, access, safety and cost.
REFERENCES: [1] Muller F, Taubmann J, Bucci L, et al. CD19 CAR T-Cell Therapy in Autoimmune Disease - A Case Series with Follow-up. N Engl J Med 2024; 390 (8): 687-700.
[2] Mackensen A, Muller F, Mougiakakos D, et al. Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Nat Med 2022; 28 (10): 2124-32.
[3] Wang W, He S, Zhang W, et al. BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial. Ann Rheum Dis 2024.
Acknowledgements: NIL.
Disclosure of Interests: Jie Gao: None declared, Yiyi Yu: None declared, Ruina Kong: None declared, Xia Xu: None declared, Suxuan Liu: None declared, Qian Chen: None declared, Xiaofang Li: None declared, Yang Wu I am employed by Rui Therapeutics, Enshun Xu I am employed by Rui Therapeutics, Ming Sun Employed by Rui Therapeutics, Jianmin Yang: None declared, Mengtao Li: None declared, Dongbao Zhao: None declared.
© The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (