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Chimeric antigen receptor T-cell (CAR-T) therapy has expanded beyond oncology and is emerging as a promising strategy for autoimmune diseases. Early clinical experience, particularly with CD19-directed CAR-T cells, has shown that deep remission can occur in refractory disorders such as systemic lupus erythematosus, inflammatory myopathies, and systemic sclerosis. These observations are consistent with an immune-reset-like process, although its durability, cellular basis, and disease-specific mechanisms remain incompletely defined. However, the clinical development landscape remains uneven. Based on an April 2026 Trialtrove snapshot, the field is growing rapidly but remains concentrated in a limited number of countries, diseases, and target classes, with most studies in early-phase development. These features suggest that autoimmune CAR-T therapy has moved beyond proof of concept, but has not yet reached a mature, indication-optimized stage of clinical translation. In this Perspective, we argue that the next phase of progress will depend less on increasing trial numbers than on improving biological precision, platform diversity, and trial design. The current pipeline is dominated by CD19-centered programs and diseases in which B-cell depletion appears biologically plausible, but this approach is unlikely to be equally informative across autoimmune disease. Key questions remain regarding remission durability, relapse after B-cell reconstitution, patient selection, toxicity management, and scalability. Looking ahead, major opportunities include plasma cell-directed approaches, dual-target strategies, chimeric autoantigen receptor platforms, tolerance-oriented cell therapies, off-the-shelf products, and in vivo engineering. The near-term readout window will be critical in determining whether autoimmune CAR-T therapy becomes broadly deployable or remains limited to selected indications and settings.
Chen et al. (Fri,) studied this question.