Emerging role of CAR-T cell therapy in autoimmune rheumatic diseases: mechanisms, clinical progress, and future directions

Autoimmune rheumatic diseases (ARDs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc), are characterized by dysregulated immune responses that lead to chronic inflammation and progressive tissue damage. Standard therapeutic approaches largely rely on broad immunosuppression, which often results in incomplete disease control and increased vulnerability to infections and other side effects. Significant advancements in immunotherapeutic strategies, most notably chimeric antigen receptor T (CAR-T) cell technology, originally developed for hematologic malignancies, have led to growing interest in their translational application to ARDs. The capacity to reset the immune system by genetically reprogramming T cells to selectively target and eliminate pathogenic B cells represents a novel and potentially transformative approach. Emerging preclinical and early-phase clinical evidence indicates that CAR-T cell therapy may enable durable disease remission or even drug-free disease quiescence in select autoimmune settings.Despite the groundbreaking success of CAR-T cell therapies in hematologic malignancies, their application in autoimmune rheumatic diseases (ARDs) remains in its infancy and presents distinct challenges. This special editorial aims to facilitate the development and clinical integration of CAR-T cells for ARDs by addressing critical issues such as antigen specificity, cell persistence, safety, and the risk of off-target effects. Furthermore, the review proposes a structured framework for the clinical application of CAR-T cell therapy in ARD populations by identifying patient subgroups most likely to benefit and outlining consensus-driven criteria to guide future implementation.Ultimately, this editorial seeks to synthesize interdisciplinary perspectives from immunology and hematology to rheumatology, bioengineering, and translational science to advance the clinical applicability of CAR-T cell therapies in ARDs. Recognizing the complexity and heterogeneity of immune dysregulation in ARDs, the initiative emphasizes the integration of mechanistic studies with clinical insights to inform precision targeting, enhance therapeutic safety, and optimize efficacy. Through this multifaceted approach, the review aims to establish a foundational framework for the evidence-based implementation of CAR-T cell therapy across diverse ARD populations.This collection explores the emerging application of CAR-T cell therapy in autoimmune rheumatic diseases (ARDs), aiming to bridge fundamental immunology and clinical translation. We invite original research, reviews, and perspectives that address therapeutic mechanisms, regulatory landscapes, and translational pathways of CAR-T in non-oncologic settings. We especially welcome interdisciplinary submissions offering bench-to-bedside insights, with the goal of advancing personalized immunotherapy for ARDs.Key themes include:• CAR-T cell-mediated immune tolerance and immune reprogramming in ARDs• Novel antigen targets and next-generation CAR-T cell constructs• Preclinical models evaluating efficacy and safety in autoimmune contexts• Algorithms or frameworks for clinical use of CAR-T in autoimmune diseases• Management of adverse events (e.g., cytokine release syndrome, immune dysregulation)• Ethical and regulatory considerations for CAR-T in non-malignant disease Topic editors: Fatima Khalid Alduraibi, Maurizio Chiriva-Internati, Fabio Grizzi Source: https://www.frontiersin.org/research-topics/74431/emerging-role-of-car-t-cell-therapy-in-autoimmune-rheumatic-diseases-mechanisms-clinical-progress-and-future-directions