CAR-T cell therapy : recent updates and challenges in autoimmune diseases.

Abstract

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the treatment of hematological malignancies, demonstrating significant clinical efficacy and leading to FDA approval of several CAR-T cell-based products. This success has prompted exploration of CAR-T cell therapy in other disease areas, including autoimmune diseases (AIDs). CAR-T cells targeting B cells have 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 cells 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 cell therapy in AIDs faces several unique challenges. The quality and functionality of T cells in patients with AIDs may be compromised due to previous treatments and the underlying inflammatory state, affecting the generation and efficacy of CAR-T cells. 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 CAR-T cell production pose economic problems, particularly in the context of chronic diseases, which are far more numerous than the hematological diseases for which CAR-Ts have been granted marketing authorization to date. If the indications for CAR-T cells increase significantly, production costs will have to drop drastically in order to obtain reliable economic models.