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

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.