Inhibition of long-lived plasma cells, a critical role for Telitacicept treatment to systemic lupus erythematosus.

IF 3 4区医学 Q3 IMMUNOLOGY

Immunopharmacology and Immunotoxicology Pub Date : 2025-10-01 Epub Date: 2025-07-30 DOI:10.1080/08923973.2025.2511761

En Zhang, Chenggang Zhao, Fengzhu Wang, Ling Wang, Shenjun Li, Jing Jiang

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引用次数: 0

Abstract

Background: Telitacicept (RC18, RemeGen, Ltd) is a novel human TACI-Fc fusion protein that combines B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). RC18 has recently been approved in China for the treatment of systemic lupus erythematosus (SLE), demonstrating its safety and efficacy in the majority of the target population. However, the unique pharmacological mechanism of RC18 has not yet been fully elucidated.

Methods: In this study, we tested MRL-/lpr mice (a classic SLE animal model) and in vitro LLPCs induced models after RC18 treatment to evaluate the factors contributing to treatment benefits.

Results: We found that RC18 delayed the progression of SLE mice by specifically targeting APRIL and long-lived plasma cells (LLPCs). In the SLE animal model, RC18 blocked proteinuria and splenic involvement. RC18 specifically downregulated LLPCs in the bone marrow (BM) compared to other immune cell types. Moreover, the deposition of immune complexes in the kidneys of the RC18 group was also reversed. In vitro, we constructed an LLPCs induction model and verified the direct regulatory ability of RC18 on LLPCs.

Conclusion: This study reveals the crucial role of LLPCs in the SLE treatment with RC18, providing a new explanation for the excellent efficacy in clinical practice.

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抑制长寿命浆细胞，是替利他赛治疗系统性红斑狼疮的关键作用。

背景：Telitacicept （RC18, RemeGen, Ltd）是一种结合B细胞活化因子（BAFF）和增殖诱导配体（APRIL）的新型人TACI-Fc融合蛋白。RC18最近在中国被批准用于治疗系统性红斑狼疮（SLE），证明其在大多数目标人群中的安全性和有效性。然而，RC18独特的药理机制尚未完全阐明。方法：在本研究中，我们对RC18治疗后的MRL-/lpr小鼠（一种经典的SLE动物模型）和体外LLPCs诱导模型进行了测试，以评估影响治疗效果的因素。结果：我们发现RC18通过特异性靶向APRIL和长寿命浆细胞（llpc）延缓SLE小鼠的进展。在SLE动物模型中，RC18阻断蛋白尿和脾脏受累。与其他免疫细胞类型相比，RC18特异性下调骨髓（BM）中的llpc。此外，RC18组肾脏中免疫复合物的沉积也被逆转。在体外，我们构建了LLPCs诱导模型，验证了RC18对LLPCs的直接调控能力。结论：本研究揭示了LLPCs在RC18治疗SLE中的关键作用，为临床疗效优异提供了新的解释。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunopharmacology and Immunotoxicology 医学-毒理学

CiteScore

5.40

自引率

0.00%

发文量

133

审稿时长

4-8 weeks

期刊介绍： The journal Immunopharmacology and Immunotoxicology is devoted to pre-clinical and clinical drug discovery and development targeting the immune system. Research related to the immunoregulatory effects of various compounds, including small-molecule drugs and biologics, on immunocompetent cells and immune responses, as well as the immunotoxicity exerted by xenobiotics and drugs. Only research that describe the mechanisms of specific compounds (not extracts) is of interest to the journal. The journal will prioritise preclinical and clinical studies on immunotherapy of disorders such as chronic inflammation, allergy, autoimmunity, cancer etc. The effects of small-drugs, vaccines and biologics against central immunological targets as well as cell-based therapy, including dendritic cell therapy, T cell adoptive transfer and stem cell therapy, are topics of particular interest. Publications pointing towards potential new drug targets within the immune system or novel technology for immunopharmacological drug development are also welcome. With an immunoscience focus on drug development, immunotherapy and toxicology, the journal will cover areas such as infection, allergy, inflammation, tumor immunology, degenerative disorders, immunodeficiencies, neurology, atherosclerosis and more. Immunopharmacology and Immunotoxicology will accept original manuscripts, brief communications, commentaries, mini-reviews, reviews, clinical trials and clinical cases, on the condition that the results reported are based on original, clinical, or basic research that has not been published elsewhere in any journal in any language (except in abstract form relating to paper communicated to scientific meetings and symposiums).