Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, United States.
Front Immunol. 2024 Oct 9;15:1465191. doi: 10.3389/fimmu.2024.1465191. eCollection 2024.
Chimeric antigen receptor (CAR) T cell therapy has become an important treatment for hematological cancers, and its success has spurred research into CAR T cell therapies for other diseases, including solid tumor cancers and autoimmune diseases. Notably, the development of CAR-based treatments for autoimmune diseases has shown great progress recently. Clinical trials for anti-CD19 and anti-BCMA CAR T cells in treating severe B cell-mediated autoimmune diseases, like systemic lupus erythematosus (SLE), have shown lasting remission thus far. CAR T cells targeting autoreactive T cells are beginning clinical trials for treating T cell mediated autoimmune diseases. Chimeric autoantigen receptor (CAAR) T cells specifically target and eliminate only autoreactive B cells, and they have shown promise in treating mucosal pemphigus vulgaris and MuSK myasthenia gravis. Regulatory CAR T cells have also been developed, which show potential in altering autoimmune affected areas by creating a protective barrier as well as helping decrease inflammation. These new treatments are only the beginning of potential CAR T cell applications in treating autoimmune disease. Novel CAR technologies have been developed that increase the safety, potency, specificity, and efficacy of CAR T cell therapy. Applying these novel modifications to autoimmune CARs has the potential to enhance the efficacy and applicability of CAR therapies to autoimmune disease. This review will detail several recently developed CAR technologies and discuss how their application to autoimmune disease will improve this emerging field. These include logic-gated CARs, soluble protein-secreting CARs, and modular CARs that enable CAR T cell therapies to be more specific, reach a wider span of target cells, be safer for patients, and give a more potent cytotoxic response. Applying these novel CAR technologies to the treatment of autoimmune diseases has the potential to revolutionize this growing application of CAR T cell therapies.
嵌合抗原受体 (CAR) T 细胞疗法已成为血液系统恶性肿瘤的重要治疗方法，其成功促使人们对 CAR T 细胞疗法治疗其他疾病（包括实体瘤和自身免疫性疾病）展开研究。值得注意的是，近年来，基于 CAR 的自身免疫性疾病治疗方法的发展取得了重大进展。在治疗严重 B 细胞介导的自身免疫性疾病（如系统性红斑狼疮 (SLE)）中，抗 CD19 和抗 BCMA CAR T 细胞的临床试验迄今为止已显示出持久缓解。针对自身反应性 T 细胞的 CAR T 细胞正在开始临床试验，用于治疗 T 细胞介导的自身免疫性疾病。嵌合自身抗原受体 (CAAR) T 细胞特异性靶向和消除仅自身反应性 B 细胞，并且在治疗黏膜寻常型天疱疮和 MuSK 重症肌无力方面显示出潜力。调节性 CAR T 细胞也已被开发出来，通过创建保护屏障以及帮助减少炎症，它们显示出改变自身免疫受影响区域的潜力。这些新的治疗方法只是 CAR T 细胞治疗自身免疫性疾病的潜在应用的开始。已经开发出新型的 CAR 技术，可提高 CAR T 细胞疗法的安全性、效力、特异性和疗效。将这些新型修饰应用于自身免疫性 CAR 有可能增强 CAR 疗法对自身免疫性疾病的疗效和适用性。本文将详细介绍几种最近开发的 CAR 技术，并讨论将其应用于自身免疫性疾病将如何改善这一新兴领域。这些技术包括逻辑门控 CAR、可溶性蛋白分泌型 CAR 和模块化 CAR，使 CAR T 细胞疗法更具特异性、覆盖更广泛的靶细胞、对患者更安全，并产生更有效的细胞毒性反应。将这些新型 CAR 技术应用于自身免疫性疾病的治疗有可能彻底改变 CAR T 细胞疗法在这一不断发展的应用领域中的地位。
