Nature系列综述：CAR-T在自身免疫疾病中异军突起，将面临哪些挑战？

Core Viewpoint - CAR-T cell therapy has shown significant effects in hematological malignancies and is expanding into clinical trials for solid tumors, infectious diseases, and autoimmune diseases, with notable advancements in treating autoimmune diseases like systemic lupus erythematosus and myasthenia gravis [2][3][5]. Industry Developments - AbbVie acquired Capstan for $2.1 billion, focusing on in vivo CAR-T therapy for autoimmune diseases, indicating a growing market interest [2]. - AstraZeneca's acquisition of EsoBiotec for $1 billion earlier this year also highlights the increasing investment in CAR-T therapies [2]. - The industry is on the brink of a breakthrough, particularly in in vivo CAR-T therapies, as evidenced by these high-value acquisitions [2]. Research Progress - The application of CAR-T therapy in autoimmune diseases began with Professor Georg Schett's team in Germany, successfully treating a patient with refractory systemic lupus erythematosus in 2021 [3]. - A recent review by Professor Schett in Nature Reviews Rheumatology discusses advancements and challenges in CAR-T therapy for autoimmune diseases, including suitable diseases and safety considerations [4][5]. Mechanism and Targeting - CAR-T therapy involves engineering immune cells to target specific antigens, primarily focusing on the depletion of pathological B cells in autoimmune diseases [6][8]. - The therapy can effectively eliminate B cells, which are central to the pathogenesis of diseases like systemic lupus erythematosus and idiopathic inflammatory myopathy [8]. - Current CAR-T therapies primarily target CD19 and BCMA, with CD38 also being a significant target for its ability to selectively eliminate antibody-producing cells [11][12]. Challenges and Considerations - The effectiveness of CAR-T therapy is influenced by the physiological mechanisms of diseases and the availability of measurable clinical endpoints, which can pose challenges in long-term studies [10]. - Certain autoimmune diseases, such as psoriasis and inflammatory bowel disease, may require alternative therapies due to the involvement of abnormal T cell activation [9]. Future Directions - The transition of CAR-T therapy from oncology to autoimmune diseases is reshaping treatment paradigms, with a focus on developing more targets and dual-target combinations to enhance safety and efficacy [13]. - Companies like Yiqiao Shenzhou are providing comprehensive CAR-T therapy development solutions to support clients through various research stages [14].