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用于系统性红斑狼疮的嵌合抗原受体T细胞疗法:现状与未来展望

CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives.

作者信息

Zhou Jincai, Lei Bixia, Shi Feifei, Luo Xinran, Wu Kai, Xu Yanhong, Zhang Yuting, Liu Rongjiao, Wang Huajing, Zhou Joy, He Xiaowen

机构信息

Innovation & Research Department, OriCell Therapeutics Co. Ltd., Shanghai, China.

出版信息

Front Immunol. 2024 Dec 19;15:1476859. doi: 10.3389/fimmu.2024.1476859. eCollection 2024.


DOI:10.3389/fimmu.2024.1476859
PMID:39749335
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11694027/
Abstract

Systemic lupus erythematosus (SLE) and lupus nephritis (LN) are debilitating autoimmune disorders characterized by pathological autoantibodies production and immune dysfunction, causing chronic inflammation and multi-organ damage. Despite current treatments with antimalarial drugs, glucocorticoids, immunosuppressants, and monoclonal antibodies, a definitive cure remains elusive, highlighting an urgent need for novel therapeutic strategies. Recent studies indicate that chimeric antigen receptor T-cell (CAR-T) therapy has shown promising results in treating B-cell malignancies and may offer a significant breakthrough for non-malignant conditions like SLE. In this paper, we aim to provide an in-depth analysis of the advancements in CAR-T therapy for SLE, focusing on its potential to revolutionize treatment for this complex disease. We explore the fundamental mechanisms of CAR-T cell action, the rationale for its application in SLE, and the immunological underpinnings of the disease. We also summarize clinical data on the safety and efficacy of anti-CD19 and anti-B cell maturation antigen (BCMA) CAR-T cells in targeting B-cells in SLE. We discuss the clinical implications of these findings and the potential for CAR-T therapy to improve outcomes in severe or refractory SLE cases. The integration of CAR-T therapy into the SLE treatment paradigm presents a new horizon in autoimmunity research and clinical practice. This review underscores the need for continued exploration and optimization of CAR-T strategies to address the unmet needs of SLE patients.

摘要

系统性红斑狼疮(SLE)和狼疮性肾炎(LN)是使人衰弱的自身免疫性疾病,其特征为病理性自身抗体产生和免疫功能障碍,会导致慢性炎症和多器官损伤。尽管目前使用抗疟药、糖皮质激素、免疫抑制剂和单克隆抗体进行治疗,但仍难以实现根治,这凸显了对新型治疗策略的迫切需求。最近的研究表明,嵌合抗原受体T细胞(CAR-T)疗法在治疗B细胞恶性肿瘤方面已显示出有前景的结果,并且可能为SLE等非恶性疾病带来重大突破。在本文中,我们旨在深入分析CAR-T疗法在SLE治疗方面的进展,重点关注其为这种复杂疾病的治疗带来变革的潜力。我们探讨了CAR-T细胞作用的基本机制、其在SLE中应用的原理以及该疾病的免疫学基础。我们还总结了抗CD19和抗B细胞成熟抗原(BCMA)CAR-T细胞在靶向SLE中的B细胞方面的安全性和有效性的临床数据。我们讨论了这些发现的临床意义以及CAR-T疗法改善重度或难治性SLE病例预后的潜力。将CAR-T疗法整合到SLE治疗模式中为自身免疫性疾病研究和临床实践展现了新的前景。这篇综述强调了持续探索和优化CAR-T策略以满足SLE患者未满足需求的必要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/168c6b593284/fimmu-15-1476859-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/ba0add86d535/fimmu-15-1476859-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/1f18d51b02e4/fimmu-15-1476859-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/b2582246b260/fimmu-15-1476859-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/9a290134527d/fimmu-15-1476859-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/e5a2d1b7ce00/fimmu-15-1476859-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/168c6b593284/fimmu-15-1476859-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/ba0add86d535/fimmu-15-1476859-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/1f18d51b02e4/fimmu-15-1476859-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/b2582246b260/fimmu-15-1476859-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/9a290134527d/fimmu-15-1476859-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/e5a2d1b7ce00/fimmu-15-1476859-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b9d4/11694027/168c6b593284/fimmu-15-1476859-g006.jpg

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CAR T-cell therapy for systemic lupus erythematosus: current status and future perspectives.

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引用本文的文献

[1]
Taming renal inflammation: signaling pathways and therapeutic advances in lupus nephritis.

BMC Nephrol. 2025-9-1

[2]
Smart CAR-T Nanosymbionts: archetypes and proto-models.

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[3]
Inhibition of DJ-1 protects from lupus onset and severity.

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[4]
CAR T-cells meet autoimmune neurological diseases: a new dawn for therapy.

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[5]
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Front Immunol. 2025-7-11

[6]
Hypoimmune CD19 CAR T cells treat allogeneic mice with features of spontaneous systemic lupus erythematosus.

iScience. 2025-5-31

[7]
Immune mediated inflammatory diseases: moving from targeted biologic therapy, stem cell therapy to targeted cell therapy.

Front Immunol. 2025-4-7

[8]
STAT3 Signaling Pathway in Health and Disease.

MedComm (2020). 2025-3-30

本文引用的文献

[1]
Application of novel CAR technologies to improve treatment of autoimmune disease.

Front Immunol. 2024

[2]
BCMA-Targeted T-Cell-Engager Therapy for Autoimmune Disease.

N Engl J Med. 2024-9-5

[3]
Clinical features of flare in Japanese patients with new-onset SLE and risk factors for SLE flare in daily clinical practice: a single-center cohort study.

Immunol Med. 2024-12

[4]
Prospects for the computational humanization of antibodies and nanobodies.

Front Immunol. 2024

[5]
Newer generations of multi-target CAR and STAb-T immunotherapeutics: NEXT CART Consortium as a cooperative effort to overcome current limitations.

Front Immunol. 2024

[6]
BCMA-CD19 compound CAR T cells for systemic lupus erythematosus: a phase 1 open-label clinical trial.

Ann Rheum Dis. 2024-9-30

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Chimeric antigen receptor T-cell infusion for large B-cell lymphoma in complete remission: a center for international blood and marrow transplant research analysis.

Leukemia. 2024-7

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Hydroxychloroquine and the associated risk of arrhythmias.

Glob Cardiol Sci Pract. 2024-3-3

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Integration of multi-omics analysis reveals metabolic alterations of B lymphocytes in systemic lupus erythematosus.

Clin Immunol. 2024-7

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Selective CAR T cell-mediated B cell depletion suppresses IFN signature in SLE.

JCI Insight. 2024-5-9

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