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.

中文翻译：

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CAR-T 细胞疗法：自身免疫性疾病的最新进展和挑战。


嵌合抗原受体 T 细胞 （CAR-T） 疗法彻底改变了血液系统恶性肿瘤的治疗，显示出显著的临床疗效，并导致 FDA 批准了几种基于 CAR-T 细胞的产品。这一成功促使 CAR-T 细胞疗法在其他疾病领域进行探索，包括自身免疫性疾病 （AIDs）。靶向 B 细胞的 CAR-T 细胞已被证明可以为难治性 AIDS 患者提供临床和生物学改善。本综述的目的是讨论 AIDS 中涉及 CAR-T 细胞的有前途的策略，例如靶向 B 细胞和 T 细胞的策略，并探索靶向成纤维细胞或浆细胞样树突状细胞的新方法。尽管取得了这些进展，但 CAR-T 细胞疗法在 AIDS 中的应用仍面临一些独特的挑战。AIDS 患者 T 细胞的质量和功能可能会因先前的治疗和潜在的炎症状态而受到影响，从而影响 CAR-T 细胞的产生和疗效。此外，在受影响的组织中实现足够的组织生物分布和 CAR-T 细胞的持久性仍然是一项重大挑战。最后，与 CAR-T 细胞生产相关的高成本带来了经济问题，尤其是在慢性病的情况下，慢性病的数量远远超过迄今为止获得 CAR-T 上市许可的血液疾病。如果 CAR-T 细胞的适应症显着增加，则生产成本将不得不大幅下降，以获得可靠的经济模型。