P187 Exploring the emerging novel therapeutic potential of chimeric antigen receptor T-cell immunotherapy for autoimmune skin disease: ‘immune reset’ potential

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of haematological malignancies and is increasingly demonstrating disease-modifying potential in refractory autoimmune disorders. Emerging evidence suggests applicability to autoimmune skin diseases, including lupus erythematosus, pemphigus vulgaris, bullous pemphigoid and severe atopic dermatitis, which share overlapping immunopathogenic mechanisms. The aim of this study was to explore and conceptually delineate the emerging therapeutic potential of CAR-T immunotherapy in autoimmune skin disease, with particular emphasis on its capacity to induce durable immune ‘reset’ rather than chronic immunosuppression. A systematic review of published clinical studies and translational literature evaluating CAR-T therapy in autoimmune disease was undertaken. Concept mapping was used to integrate mechanistic insights, early clinical outcomes and evidence from dermatology, haematology and neuroimmunology. Autoimmune skin diseases are frequently driven by autoreactive B cells, pathogenic T-cell subsets and dysregulated immune memory, resulting in sustained autoantibody production and chronic inflammation. Recent studies demonstrate that targeted immune cell ablation followed by immune reconstitution can induce long-term disease quiescence. In neuroimmunology, particularly multiple sclerosis, immune reprogramming strategies have shown sustained remission. Early clinical data using CD19-directed CAR-T therapy in antibody-mediated autoimmune disease report profound depletion of autoreactive B cells and durable remission. One study of systemic lupus erythematosus (13 patients) demonstrated drug-free remission with symptom-free periods lasting up to 46 months. A small pemphigus vulgaris trial reported rapid and clinically meaningful reductions in Pemphigus Disease Area Index within 1 month, alongside significant B-cell reduction. Emerging approaches, including antigen-specific CAR-T platforms and CAR-T regulatory cell therapies, aim to selectively eliminate disease-driving immune populations while preserving global immune competence. Although still in early clinical development, CAR-T therapy represents a promising shift towards curative, precision immunotherapy for severe, refractory autoimmune skin disease. Despite limitations including small trial sizes and uncertain long-term safety, advances in antigen specificity, low-intensity conditioning regimens and safety-enhanced CAR-T designs offer significant future potential.