Chimeric Antigen Receptor T Cell Immunotherapy for Autoimmune Rheumatic Disorders: Where Are We Now?

Abstract

Chimeric antigen receptor (CAR) T cell immunotherapy has changed the landscape of B cell hematological malignancies' management, while it has recently shown promising results in the treatment of refractory autoimmune rheumatic disorders (ARDs). Targeting B cell antigens such as CD19 and BCMA, CAR-T cell therapy can induce sustained remission by the elimination of autoreactive B cell populations resistant to the standard of care treatment options. Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIMs), rheumatoid arthritis (RA), antiphospholipid syndrome (APS), and primary Sjögren's syndrome (pSS). Treatment outcomes include reduced disease activity, normalization of serologic markers, improved organ function, and drug-free remission, even after B cell reconstitution. Additionally, toxicities, primarily limited to mild cytokine release syndrome (CRS), were generally manageable with supportive care. Encouraging preliminary results have led to the development of several ongoing clinical trials investigating CAR-T cell therapy across multiple ARDs and patient populations, including pediatric patients. This review summarizes the current clinical experience and provides a comprehensive overview of ongoing clinical trials exploring CAR-T cell immunotherapy for ARDs.

Keywords: BCMA; CAR-T cell therapy; CD19; autoimmune rheumatic disorders; immunotherapy; systemic lupus erythematosus.

Figure 1

Mapping of the stages of B cell development—from early pro-B cells in the bone marrow through germinal center maturation to long-lived plasma cells—and highlighting of the surface antigens (e.g., CD19, CD20, BCMA) exploited by current CAR-T constructs. Moreover, the schematic illustrates how choice of antigen influences both the breadth of B-lineage deletion and the potential for on-target, off-tumor effects on normal B cell subsets. BCMA: B cell maturation antigen; CAR: chimeric antigen receptor T (created in BioRender. Evangelidis, P. (2025) https://BioRender.com/p17x35i).

Figure 2

This diagram contrasts the activity of CD19-directed versus BCMA-directed CAR-T cells: anti-CD19 CAR-T targets CD19⁺ B cells at all developmental stages up to the plasma blast phase, while anti-BCMA CAR-T selectively targets BCMA⁺ plasma cells. It depicts CAR engagement, immunological synapse formation, and downstream cytotoxic pathways—perforin/granzyme release and death-receptor signaling—leading to the elimination of pathogenic B-lineage cells. BCMA: B cell maturation antigen; CAR: chimeric antigen receptor T (created in BioRender. Evangelidis, P. (2025) https://BioRender.com/86mtefl).