Chimeric antigen receptor-T (CAR-T) cell therapy is a genetically engineered approach that introduces synthetic receptor molecules into T cells, enabling them to specifically recognize and target antigenic epitopes, thereby enhancing the recognition of antigenic signals and activation of T lymphocytes [1]. CAR-T cell therapy was initially developed for the treatment of hematological malignancies [2], and ongoing refinements aim to improve their cytotoxic efficacy through strategies such as enhancing T-cell persistence, suppressing inhibitory receptor expression, and mitigating immune escape mechanisms [3,4]. CAR-T cells have achieved remarkable breakthroughs in the treatment of hematologic malignancies, particularly in relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM) [5]. Furthermore, their application has gradually extended to solid tumors, establishing CAR-T therapy as a crucial component of precision oncology [6,7]. Currently, the US Food and Drug Administration (FDA) has approved seven types of CAR-T cell therapies for tumor treatment, primarily targeting CD19 or BCMA. These therapies have shown high complete remission rates, with a significant proportion of patients achieving progression-free survival (PFS) exceeding 5 years [[5], [6], [7]]. The success of CAR-T cells has generated significant interest in exploring their potential applications in other B-cell mediated diseases, such as autoimmune diseases.

Autoimmune diseases represent a diverse group of conditions characterized by an imbalanced immune system that abnormally attacks the cells and tissues of the body, loss of immune tolerance to autoantigens, and impaired self-nonself discrimination [8]. Multiple autoimmune diseases are predominantly mediated by self-reactive B cells. These cells contribute to disease pathogenesis through the production of pathogenic autoantibodies and the promotion of disease recurrence [9,10]. Current therapeutic strategies may be limited by their inability to fully penetrate target tissues and achieve comprehensive eradication of autoreactive B cell clones [11,12]. Owing to their autonomous functionality, deep tissue-penetrating capacity, and potent B-cell depletion effects, CAR-T cell therapy has emerged as a predominant investigational focus for autoimmune diseases, with accumulating clinical evidence substantiating its therapeutic efficacy and favorable safety profile [13].

In this comprehensive review, we discuss emerging cellular therapeutic strategies, with a particular focus on B-cell-targeting CAR T-cell therapies, and critically assess their transformative potential in reshaping treatment paradigms for autoimmune diseases. Furthermore, we summarize ongoing clinical trials evaluating CAR-T cell therapy, which provide initial evidence regarding the feasibility, safety, and efficacy of this innovative approach. Additionally, we emphasize that future strategies should be developed to broaden the application and enhance the safety of CAR-T cell therapy in autoimmune diseases, such as utilizing chimeric autoantibody receptors to selectively deplete autoantigen-specific B cells.