The advent of chimeric antigen receptor (CAR) T-cells has revolutionized the treatment landscape for hematologic malignancies, and emerging evidence suggests their potential in autoimmune diseases (AIDs). This article examines the early successes and future implications of B-cell-targeting CAR T-cell therapy in AIDs. Initial applications, particularly in refractory systemic lupus erythematosus (SLE), have demonstrated significant and durable clinical remissions, with accompanying evaluation of the immune system suggesting a so-called "reset" of innate inflammation and adaptive autoimmunity. This has generated widespread interest in expanding this therapeutic approach. CAR T-cells offer unique advantages over other treatment modalities, including very deep B-cell depletion and unique therapeutic activity within inflamed tissues and associated lymph structures. However, the field must address key concerns, including long-term toxicity, particularly the risk of secondary malignancies, and future accessibility given the higher prevalence of AIDs compared to malignancies. Technological advances in cell therapy, such as next-generation CAR T-cells, allogeneic off-the-shelf products and alternative cell types such as regulatory CAR T-cells, are being explored in AIDs to improve efficacy and safety. In addition, bispecific antibodies are emerging as potential alternatives or complements to CAR T-cells, potentially offering comparable efficacy without the need for complex logistics, lymphodepletion and the risk of insertional mutagenesis. As the field evolves, cellular therapists will play a critical role in the multidisciplinary teams managing these complex cases. The transformative potential of CAR T-cells in AIDs is undeniable, but careful consideration of safety, efficacy, and implementation is essential as this novel therapeutic approach moves forward.

中文翻译：

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自身免疫中的 CAR T 细胞：改变游戏规则还是垫脚石？


嵌合抗原受体 （CAR） T 细胞的出现彻底改变了血液系统恶性肿瘤的治疗格局，新出现的证据表明它们在自身免疫性疾病 （AIDs） 中的潜力。本文探讨了 B 细胞靶向 CAR T 细胞疗法在 AIDS 中的早期成功和未来影响。初始应用，特别是在难治性系统性红斑狼疮 （SLE） 中，已显示出显著且持久的临床缓解，伴随的免疫系统评估表明先天性炎症和适应性自身免疫的所谓“重置”。这引起了人们对扩展这种治疗方法的广泛兴趣。与其他治疗方式相比，CAR T 细胞具有独特的优势，包括非常深的 B 细胞耗竭和在发炎组织和相关淋巴结构内的独特治疗活性。然而，该领域必须解决关键问题，包括长期毒性，特别是继发性恶性肿瘤的风险，以及鉴于 AIDS 的患病率高于恶性肿瘤，未来的可及性。正在 AID 中探索细胞疗法的技术进步，例如下一代 CAR T 细胞、同种异体现成产品和替代细胞类型，例如调节性 CAR T 细胞，以提高疗效和安全性。此外，双特异性抗体正在成为 CAR T 细胞的潜在替代品或补充，可能提供相当的疗效，而无需复杂的物流、淋巴细胞耗竭和插入诱变的风险。随着该领域的发展，细胞治疗师将在管理这些复杂病例的多学科团队中发挥关键作用。 CAR T 细胞在 AIDS 中的变革潜力是不可否认的，但随着这种新型治疗方法的发展，仔细考虑安全性、有效性和实施至关重要。