CAR-based cellular therapies for autoimmune diseases: immune reset, clinical evidence, and translational boundaries.
CAR-based cellular therapy is emerging as a time-limited strategy for severe autoimmune disease, but its clinical value depends on more than early response. We conducted a structured narrative review with a targeted update of PubMed/MEDLINE and ClinicalTrials.gov through July 11, 2026, with study-level extraction and explicit handling of overlapping cohorts. Autologous CD19 CAR-T has the most mature evidence, particularly in systemic lupus erythematosus and other systemic rheumatic diseases, while one randomized phase 2b trial has evaluated transient mRNA BCMA-directed CAR-T in myasthenia gravis. Early studies also support disease-specific development in systemic sclerosis, idiopathic inflammatory myopathy, rheumatoid arthritis, autoimmune cytopenias, and selected neurologic disorders. However, cohorts remain small and heterogeneous, and severe cytokine release syndrome, neurotoxicity, hematotoxicity, infection, viral reactivation, hypogammaglobulinemia, and prolonged organ dysfunction have been reported. Immune reset should therefore be treated as a testable multidomain state: durable disease control after the acute treatment phase, withdrawal of conventional immunosuppression, evolution or recovery of the targeted immune compartment without immediate pathogenic recurrence, and preservation of clinically acceptable immune competence. It is not synonymous with cure, continued aplasia, complete autoantibody eradication, or reversal of fixed organ damage. Future development requires disease-specific comparative trials, biomarker-guided platform selection, standardized clinical and immune-reconstitution endpoints, transparent reporting of manufacturing attrition and cohort overlap, experienced multidisciplinary delivery, and long-term registries capturing infection, fertility, neurologic outcomes, secondary malignancy, relapse, retreatment, and patient-centered value. Until these data mature, autoimmune CAR therapy should remain investigational and restricted to highly selected patients in prospective programs.