通用型CAR-NK细胞治疗系统性红斑狼疮的应用与展望

Application and prospect of universal CAR-NK cell therapy for systemic lupus erythematosus

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。

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.