Beyond Hematology—Current Insights into Chimeric Antigen Receptor (CAR) T Cell Therapy for Skin and Connective Tissue Disorders

Chimeric antigen receptor (CAR) T cell therapy represents one of the greatest breakthroughs in modern immunotherapies. To date, it has been approved by the Food and Drug Administration (FDA) for the treatment of several hematological malignancies, including different subtypes of leukemia, lymphoma, and multiple myeloma. However, recent reports suggest that CAR T therapy may also be effective in the treatment of severe systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Case reports and small case series have demonstrated the efficacy of anti-CD19 CAR T cell therapy while maintaining a favorable safety profile. The most frequently reported adverse events include grade 1 or 2 cytokine release syndrome (CRS), hypogammaglobulinemia, and mild infectious complications. Moreover, CAR T therapy may also have potential in the treatment of advanced metastatic solid tumors, including melanoma. Early clinical studies have demonstrated the feasibility and safety of CAR T cell therapy in metastatic melanoma; however, several challenges remain. These include limited tumor trafficking and infiltration of CAR T cells, due to the presence of an immunosuppressive tumor microenvironment. Additionally, following the remarkable success of CAR T therapy in lymphomas, this approach may also be applied to the treatment of cutaneous lymphomas, including cutaneous T-cell and B-cell lymphomas. Key challenges include tumor heterogeneity, optimal target antigen selection, fratricidal activity of CAR T cells, and potential contamination of the CAR T product with lymphoma cells.