协和医学杂志

2020, v.11(03) 241-246

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系统性红斑狼疮新型生物治疗靶点:希望与挑战
New Biologic Targets for Systemic Lupus Erythematosus:Hope and Challenge

杨华夏;张奉春;
YANG Hua-xia;ZHANG Feng-chun;Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education,Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College;

摘要(Abstract):

随着贝利木单克隆抗体(肿瘤坏死因子家族B细胞活化因子拮抗剂)在中国用于治疗系统性红斑狼疮(systemic lupus erythematosus, SLE)适应证的获批,SLE的治疗逐渐迈向了生物制剂时代。SLE发病机制复杂,包括B细胞和T细胞免疫耐受机制的破坏。本文关注SLE的新型生物治疗靶点,以及正在进行的SLE临床试验,围绕靶向B细胞特异性表面分子(CD20、CD19),靶向B细胞信号通路和细胞因子(肿瘤坏死因子家族B细胞活化因子、增值诱导配体),靶向共刺激因子减少B细胞抗原呈递(CD40及其配体、可诱导共刺激分子及其配体),以及T细胞及信号通路(rigerimod、干扰素α、JAK-STAT)等SLE相关靶标展开讨论。总而言之,生物靶向治疗SLE已获得一定进展,未来前景可期。
Belimumab is a human monoclonal antibody that inhibits B-cell activating factor of the tumor necrosis factor family(BAFF). With the approval of belimumab for treating patients with systemic lupus erythematosus(SLE), targeted biologics has generally ushered a new era in the treatment of SLE. The pathogenesis of SLE involves a general breakdown in both B cell and T cell tolerance. In this review, we focused on the new promising therapeutic targets and several ongoing clinical trials for SLE. The approaches of these biologic therapeutic agents included targeting B cell selective cell surface molecules(CD20 or CD19), inhibiting B cell survival by targeting cytokines and signaling molecules(BAFF or a proliferation-inducing ligand), interfering with B cell antigen presentation by targeting co-stimulatory molecules(CD40-CD40 ligand interactions or ICOS-ICOS ligand interactions), blocking the signal pathways(rigerimod, interferon-α, or JAK/STAT), et al. Biologic target therapies for SLE have made some progress and bringing successful new biologic therapies into the clinical practice for SLE remains challenging but promising in the future.

关键词(KeyWords): 系统性红斑狼疮;生物制剂;治疗靶点;临床试验
systemic lupus erythematosus;biologics;therapeutic target;clinical trial

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基金项目(Foundation): 国家自然科学基金(81801633)

作者(Author): 杨华夏;张奉春;
YANG Hua-xia;ZHANG Feng-chun;Department of Rheumatology and Clinical Immunology, National Clinical Research Center for Dermatologic and Immunologic Diseases,Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education,Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College;

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