Chimeric antigen receptor-modified T-cell therapy: Recent updates and challenges in autoimmune diseases.

Abstract

Chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has revolutionized the treatment of hematologic malignancies, demonstrating significant clinical efficacy and leading to US Food and Drug Administration approval of several CAR T-cell-based products. This success has prompted exploration of CAR-T in other disease areas, including autoimmune diseases (AIDs). CAR-T targeting B cells has been shown to provide clinical and biological improvements in patients with refractory AIDs. The aim of this review is to discuss promising strategies involving CAR-T in AIDs, such as those targeting B cells and T cells, and to explore new approaches targeting fibroblasts or plasmacytoid dendritic cells. Despite these advances, the application of CAR-T in AIDs faces several unique challenges. The quality and functionality of T cells in patients with AIDs may be compromised as a result of previous treatments and the underlying inflammatory state, affecting the generation and efficacy of CAR-T. In addition, achieving adequate tissue biodistribution and persistence of CAR T cells in affected tissues remains a major challenge. Finally, the high costs associated with T-cell production pose economic problems, particularly in the context of chronic diseases, which are far more numerous than the hematologic diseases for which CAR-Ts have been granted marketing authorization to date. If the indications for CAR-T increase significantly, production costs will have to drop drastically in order to obtain reliable economic models.