Systemic lupus erythematosus (SLE) is a multisystem involvement, highly heterogeneous autoimmune disease with complex pathogenesis and good occurrence in women of childbearing age. The clinical manifestations of SLE are highly heterogeneous, with different systemic involvement, varying disease course and disease severity, and can manifest as fever, skin mucosa and musculoskeletal damage or involvement of multiple body organs including kidneys, lung and heart.
In terms of treatment, therapeutic agents for SLE include [1] including hormones, antimalarials, immunosuppressants and biological agents. However, many patients not only need long-term medication, but also still can not control the condition after medication, unable to achieve long-term remission. In recent years, studies have found that CAR-T cell therapy targeting CD19 has good results in SLE and can achieve long-term remission.
CAR-T-cell therapy is a T-cell-based genetic engineering therapy that can genetically engineer T cells to recognize CD19 and other antigens on the surface of B cells, and then target B cells, which is very effective for the treatment of B-cell malignancies. So far, a number of CAR-T cell therapies have been approved, mainly for the treatment of blood tumors.
Back in 2021, a clinical study published in the New England Journal of Medicine (NEJM) showed that a 20-year-old woman with severe SLE with multiple drugs who was first treated with CAR-T cell therapy rapidly alleviated [2].
Figure: CAR-T cell therapy in patients with resistant SLE
Subsequently, a study published in nature medicine in 2022 showed that after treatment of five SLE patients by CAR T cell therapy, all patients achieved remission of SLE after 3 months and had no relapse at up to seventeen-months of [3].
Figure: CAR-T cell expansion in vivo and depletion of B cells
At the annual meeting of the American society of hematology in 2023, a study on CAR T cell therapy for 15 autoimmune disease patients showed that 15 patients with autoimmune diseases (including 8 patients with systemic lupus erythematosus, 4 systemic sclerosis and 3 idiopathic inflammatory myopathy) after CAR-T cell therapy "rebirth", patients with disease symptoms significantly improved, and achieve lasting no drug relief. All 8 patients with SLE achieved complete remission after 3 months and thereafter consistently maintained the SLE disease activity index (SLEDAI) of 0 [4].
It is worth mentioning that in 2023, CAR-T immune cell therapy (marketed in China in 2021) was approved in clinical trials for the treatment of moderate to severe refractory SLE, in order to bring a new treatment plan for SLE patients [5].
Photo: The Drug Review Center of the National Medical Products Administration
In addition to the good results of clinical research, many domestic hospitals have also achieved good results in CAR-T treatment of SLE. Such as [6]:
In March 2024, the Children's Hospital Affiliated to Zhejiang University School of Medicine and other teams used CAR-T therapy to treat 12-year-old refractory SLE patients with good efficacy. The child has been discharged smoothly and is expected to be completely cured.
In April 2024, the Department of Rheumatology and Immunology of Wuhan Union Hospital used universal CD19 CAR- γδ T to treat patients with severe SLE. 28 days after three transfusion of CAR- γδ T cells, the SLE disease activity index score decreased to 5, which significantly decreased compared with that before transfusion, and they did not take any other SLE drugs during the period.
In April 2024, the Department of Rheumatology of the First Affiliated Hospital of Zhejiang University School of Medicine used targeted CD19 universal CAR-T cells to treat patients with refractory SLE, whose SLEDAI score decreased from 18 points before treatment to 0, and all hormones and immunosuppressive agents were gradually discontinued.
On May 8,2024, the first CAR-T cell immunotherapy clinic in Central China was officially opened in Wuhan Union Hospital, integrating multidisciplinary expert resources to provide individualized and accurate diagnosis and treatment plans for patients with multiple myeloma, lymphoma, leukemia, SLE and other patients.
With the continuous improvement of medical technology level, CAR-T cell therapy has achieved good efficacy in the research treatment of patients with severe SLE. It is expected that this therapy will continue to create miracles, bring the hope of "cure" for SLE patients, and achieve long-term drug-free remission.
It was edited and organized by the China Continuing Medical Education Network
reference material:
[1] Shen Nan, Zhao Yi, Duan Lihua, et al. Practice for the diagnosis and treatment of systemic lupus erythematosus [J]. Chinese Journal of Internal Medicine, 2023,62 (7): 775-784. DOI: 10.3760/cma.j.cn112138-20221027-00793.
[2] Dimitrios Mougiakakos, M.D.Gerhard Krönke, et al.M.D.CD19-Targeted CAR T Cells in Refractory Systemic Lupus Erythematosus.N Engl J Med 2021;385:567-569
[3] Mackensen, Müller, Mougiakakos.et al.Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus.Nat Med 28, 2124–2132 (2022).https://doi.org/10.1038/s41591-022-02017-5
[4] Fabian Mueller MD, Jule Taubmann MD.et al.CD19-Targeted CAR-T Cells in Refractory Systemic Autoimmune Diseases: A Monocentric Experience from the First Fifteen Patients.Volume 142, Supplement 1, 2 November 2023, Page 220
[5] The Drug Review Center of the National Medical Products Administration
[6] Wuhan Union Hospital, Wuhan Union Hospital Department of Rheumatology, Zhejiang University Hospital, Zhejiang a blood public number
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