Chimeric antigen receptor T-cell (CAR-T) therapy and other cellular immunotherapy treatments for idiopathic inflammatory myopathies

IF 7 2区医学 Q1 RHEUMATOLOGY

Best Practice & Research in Clinical Rheumatology Pub Date : 2026-03-01 Epub Date: 2026-05-18 DOI:10.1016/j.berh.2026.102140

Jisna R. Paul , Prateek C. Gandiga , Rohit Aggarwal

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引用次数: 0

Abstract

Idiopathic inflammatory myopathies (IIM), including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), anti-synthetase syndrome (ASyS), overlap myositis and polymyositis, are heterogeneous autoimmune diseases characterized by immune-mediated skeletal muscle injury and frequent extra-muscular organ involvement. Despite recent therapeutic advances, many IIM patients have persistent disease activity, medication toxicity, or steroid dependence with current treatments. Increasing evidence implicates autoreactive B cells and autoantibody-producing plasma cells as central drivers of disease activity in several IIM subtypes, providing a strong rationale for B-cell– targeted therapies. While monoclonal antibody–based B-cell depletion strategies such as rituximab have demonstrated variable efficacy, their inability to effect persistent, intense depletion of tissue autoreactive B-cell populations often limit their success.

Chimeric antigen receptor T-cell (CAR-T) and related cellular immunotherapies were originally developed against hematologic malignancies, but have recently emerged potentially transformative therapeutic options for autoimmune diseases. CAR-T cells targeting CD19 and other B-cell antigens have demonstrated the capacity to induce deep and durable B-cell depletion, and may even lead to “immune reset” with long-lived autoimmunity remission in diseases such as systemic lupus erythematosus and systemic sclerosis. Early clinical experiences now suggest that CAR-T therapy may offer similar promise in refractory IIM, particularly in phenotypes that include pathogenic autoantibodies, such as ASyS, DM, IMNM.

This review provides a synopsis of current knowledge on the immunopathogenesis of IIM relevant to CAR-T and other cellular immunotherapy, outlines CAR-T technology and the mechanistic rationale for its use in IIM, and critically appraises emerging clinical CAR-T treatment data in IIM. We also discuss safety considerations, practical challenges, and future directions, with a focus on how CAR-based immunotherapies may reshape treatment paradigms for refractory inflammatory myopathies.

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嵌合抗原受体t细胞（CAR-T）疗法和其他细胞免疫疗法治疗特发性炎性肌病。

特发性炎症性肌病（IIM），包括免疫介导的坏死性肌病（IMNM）、皮肌炎（DM）、抗合成酶综合征（ASyS）、重叠性肌炎和多发性肌炎，是一种异质性自身免疫性疾病，其特征是免疫介导的骨骼肌损伤和频繁的肌外器官受累。尽管最近的治疗进展，许多IIM患者有持续的疾病活动，药物毒性，或类固醇依赖与目前的治疗。越来越多的证据表明，自身反应性B细胞和产生自身抗体的浆细胞是几种IIM亚型疾病活动的主要驱动因素，这为B细胞靶向治疗提供了强有力的理论依据。虽然基于单克隆抗体的b细胞消耗策略（如利妥昔单抗）已显示出不同的功效，但它们无法持续、强烈地消耗组织自身反应性b细胞群，这往往限制了它们的成功。嵌合抗原受体t细胞（CAR-T）和相关的细胞免疫疗法最初是针对血液系统恶性肿瘤开发的，但最近出现了潜在的自身免疫性疾病的变革性治疗选择。靶向CD19和其他b细胞抗原的CAR-T细胞已经证明能够诱导深度和持久的b细胞耗损，甚至可能导致“免疫重置”，在系统性红斑狼疮和系统性硬化症等疾病中实现长期的自身免疫缓解。早期临床经验表明，CAR-T疗法可能在难治性IIM中提供类似的前景，特别是在包括致病性自身抗体的表型中，如ASyS， DM， IMNM。本文综述了目前与CAR-T和其他细胞免疫疗法相关的IIM免疫发病机制的知识，概述了CAR-T技术及其在IIM中使用的机制原理，并批判性地评价了IIM中出现的临床CAR-T治疗数据。我们还讨论了安全性考虑、实际挑战和未来方向，重点是基于car的免疫疗法如何重塑难治性炎症性肌病的治疗范式。

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

Best Practice & Research in Clinical Rheumatology 医学-风湿病学

CiteScore

9.40

自引率

0.00%

发文量

审稿时长

27 days

期刊介绍： Evidence-based updates of best clinical practice across the spectrum of musculoskeletal conditions. Best Practice & Research: Clinical Rheumatology keeps the clinician or trainee informed of the latest developments and current recommended practice in the rapidly advancing fields of musculoskeletal conditions and science. The series provides a continuous update of current clinical practice. It is a topical serial publication that covers the spectrum of musculoskeletal conditions in a 4-year cycle. Each topic-based issue contains around 200 pages of practical, evidence-based review articles, which integrate the results from the latest original research with current clinical practice and thinking to provide a continuous update. Each issue follows a problem-orientated approach that focuses on the key questions to be addressed, clearly defining what is known and not known. The review articles seek to address the clinical issues of diagnosis, treatment and patient management. Management is described in practical terms so that it can be applied to the individual patient. The serial is aimed at the physician in both practice and training.