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泰吉华单抗:靶向自身免疫和风湿性疾病的新突破。

Telitacicept: A novel horizon in targeting autoimmunity and rheumatic diseases.

作者信息

Zeng Liuting, Yang Kailin, Wu Yang, Yu Ganpeng, Yan Yexing, Hao Moujia, Song Tian, Li Yuwei, Chen Junpeng, Sun Lingyun

机构信息

Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Graduate School of Peking Union Medical College, Nanjing, China.

Key Laboratory of Hunan Province for Integrated Traditional Chinese and Western Medicine on Prevention and Treatment of Cardio-Cerebral Diseases, School of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, China; Psychosomatic laboratory, Department of Psychiatry, Daqing Hospital of Traditional Chinese Medicine, Daqing, China.

出版信息

J Autoimmun. 2024 Sep;148:103291. doi: 10.1016/j.jaut.2024.103291. Epub 2024 Aug 14.

Abstract

BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.

摘要

B淋巴细胞刺激因子(BLyS)和增殖诱导配体(APRIL)能够在体内与B细胞结合,使这些细胞在本应自然清除时逃避清除。虽然BLyS主要在B细胞发育和成熟中发挥作用,但APRIL与B细胞活化及抗体分泌有关。因此,从理论上讲,抑制BLyS或APRIL可以减少导致系统性红斑狼疮(SLE)的异常B细胞数量,并降低患者的疾病活动度。泰它西普通过结合并中和BLyS和APRIL的活性发挥作用,从而阻碍浆细胞和成熟B细胞的成熟与存活。泰它西普的设计独特;它不是单克隆抗体,而是通过重组DNA技术产生的一种跨膜激活剂和钙调亲环素配体相互作用分子(TACI)-Fc融合蛋白。这种融合涉及将能够同时靶向BLyS/APRIL的TACI蛋白的基因片段与人IgG蛋白的Fc基因片段合并。TACI-Fc融合蛋白展现出这两种蛋白的综合特性。泰它西普目前用于自身免疫性疾病治疗,正在全球范围内进行临床研究,以评估其在治疗各种自身免疫性疾病方面的疗效。这篇综述整合了关于泰它西普(一种双靶点生物制剂)的作用机制、给药方案、药代动力学、疗效和安全性概况的信息。它整合了先前在类风湿关节炎(RA)和SLE治疗中的实验结果和药代动力学分析结果,力求全面概述泰它西普的研究进展。

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