CAR T-cell therapy: perspectives for dermatology

Chimeric antigen receptor (CAR) T-cell therapy has rapidly emerged as a groundbreaking development in oncology and is increasingly being investigated for autoimmune diseases, including dermatological conditions. CAR T-cells are genetically engineered immune cells that express a synthetic receptor combining an antibody-derived extracellular domain with intracellular signaling components of the T-cell receptor and co-stimulatory domains. This chimeric design enables highly specific recognition and elimination of target cells.

In haematological malignancies, such as B-cell lymphomas, CAR T-cell therapy directed against CD19 has demonstrated profound efficacy, even in patients refractory to multiple lines of treatment. Compared to monoclonal antibodies, CAR T-cells achieve deeper and more durable B-cell depletion. However, treatment is complex and costly, requiring autologous cell collection, ex vivo modification, and reinfusion after several weeks of production. Despite its transformative potential, CAR T-cell therapy is associated with significant risks, including cytokine release syndrome, neurotoxicity, haematological adverse events, and, rarely, CAR T-cell–associated lymphoma. Nonetheless, in patients without alternative treatment options, these risks are considered acceptable, and outcomes have been highly encouraging.

Recent developments extend CAR technology into autoimmunity. In pemphigus vulgaris, chimeric autoantigen receptor (CAAR) T-cells are designed to express the relevant autoantigen, enabling selective elimination of pathogenic autoreactive B-cells. This strategy offers deeper and more specific depletion than conventional B-cell–directed therapies, with the potential to fundamentally alter disease course. In parallel, regulatory T-cells engineered with CARs (CAR Tregs) are being developed to re-establish immune tolerance by suppressing autoreactive lymphocytes, thereby offering a safer and more targeted approach to chronic autoimmune diseases.

Beyond oncology and autoimmunity, CAR T-cell research is expanding into solid tumours, fibrotic diseases, infections, and even senescence-associated pathologies. While solid tumour applications remain challenging due to antigen heterogeneity, immune escape, and off-target effects, advances in receptor engineering and manufacturing strategies continue to improve feasibility. A further distinction arises between ex vivo–engineered autologous or allogeneic CAR T-cells and in vivo generation using viral vectors or mRNA-loaded nanoparticles. The latter, particularly transient CAR expression via mRNA, may be especially attractive for autoimmune indications, where durable T-cell persistence is undesirable.

Although currently limited by cost, manufacturing complexity, and safety considerations, CAR T-cell therapies are expected to transition progressively from experimental interventions for refractory disease to broader clinical applications. For dermatology, where autoimmune blistering diseases such as pemphigus vulgaris remain difficult to manage, CAR T-cell–based approaches may offer a paradigm shift. Early data suggest high specificity, reduced side effects compared to oncology settings, and the potential to redefine the therapeutic landscape in immune-mediated skin disease.