| 摘要: |
| 系统性红斑狼疮（SLE）的特点是B细胞异常活化产生大量自身抗体，这些自身抗体与自身抗原形成免疫复合物诱发系统性炎症，导致全身多系统多器官受累。现有靶向B细胞治疗策略（如贝利尤单抗、泰它西普及利妥昔单抗等）的临床疗效仍然有限，近年来靶向CD19的嵌合抗原受体（CAR）-T细胞治疗SLE展现出卓越的疗效。但自体CAR-T细胞治疗存在细胞因子释放综合征、T细胞肿瘤、感染等潜在风险，且价格昂贵。CAR-自然杀伤（NK）细胞治疗是现货型细胞疗法，其安全性高，无神经毒性及肿瘤化风险，且治疗费用低。目前，CAR-NK细胞在治疗血液系统肿瘤中取得了显著的研究成果，且CAR-NK细胞治疗SLE的初步临床研究展现出良好的治疗效果、优异的安全性及可预期的持久性。本文将重点阐述新一代通用型CAR-NK细胞的特点及其用于治疗复发难治性SLE的最新临床研究结果，展望其治疗SLE及B细胞相关自身免疫病的广阔前景。 |
| 关键词: 系统性红斑狼疮 嵌合抗原受体 自然杀伤细胞 通用型 |
| DOI：10.16781/j.CN31-2187/R.20240262 |
| 投稿时间：2024-04-22修订日期：2024-07-01 |
| 基金项目:上海市卫生健康委员会卫生行业临床研究专项（202340061），海军军医大学（第二军医大学）第一附属医院“十四五”学科固海计划（GH145-34）. |
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| Application and prospect of universal CAR-NK cell therapy for systemic lupus erythematosus |
| YU Yiyi,HU Jiaqi,JIN Zhengyi,KONG Ruina,GAO Jie* |
(Department of Rheumatology and Immunology, The First Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Systemic lupus erythematosus (SLE) is characterized by a large number of anti-autoantibodies produced by abnormally activated B cells, which form immune complexes with autoantigens to induce systemic inflammation, leading to the involvement of multiple systems and organs. Existing treatment strategies targeting B cells (such as belimumab, telitacicept, and rituximab) had limited efficacy. Recently, CD19 targeting chimeric antigen receptor (CAR)-T cell has shown excellent efficacy in the treatment of SLE. However, autologous CAR-T cell therapy has potential risks such as cytokine release syndrome (CRS), T cell tumors, and infections, and it is expensive. CAR-natural killer (NK) cell therapy, on the other hand, is an off-the-shelf cellular therapy with high safety, no neurotoxicity or tumorigenic risk, and with low treatment costs. Currently, CAR-NK cell has achieved remarkable research results in treating hematological malignancies, and preliminary clinical studies of CAR-NK cell therapy for SLE have showed good efficacy, excellent safety, and predictable durability. This article focuses on the characteristics of the new generation of universal CAR-NK cell and the latest clinical research results for the treatment of relapsed and refractory SLE, offering insights into its promising future in the treatment of SLE and B-cell-related autoimmune diseases. |
| Key words: systemic lupus erythematosus chimeric antigen receptor natural killer cells universal type |
