Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Nature. 2023 Jul;619(7971):707-715. doi: 10.1038/s41586-023-06243-w. Epub 2023 Jul 26.
Engineering a patient's own T cells to selectively target and eliminate tumour cells has cured patients with untreatable haematologic cancers. These results have energized the field to apply chimaeric antigen receptor (CAR) T therapy throughout oncology. However, evidence from clinical and preclinical studies underscores the potential of CAR T therapy beyond oncology in treating autoimmunity, chronic infections, cardiac fibrosis, senescence-associated disease and other conditions. Concurrently, the deployment of new technologies and platforms provides further opportunity for the application of CAR T therapy to noncancerous pathologies. Here we review the rationale behind CAR T therapy, current challenges faced in oncology, a synopsis of preliminary reports in noncancerous diseases, and a discussion of relevant emerging technologies. We examine potential applications for this therapy in a wide range of contexts. Last, we highlight concerns regarding specificity and safety and outline the path forward for CAR T therapy beyond cancer.
工程化患者自身的 T 细胞以选择性地靶向和消除肿瘤细胞已经治愈了患有难治性血液系统癌症的患者。这些结果激发了该领域将嵌合抗原受体 (CAR) T 疗法应用于整个肿瘤学领域的热情。然而,临床前和临床研究的证据强调了 CAR T 疗法在治疗自身免疫、慢性感染、心脏纤维化、衰老相关疾病和其他疾病方面的潜力超出了肿瘤学领域。与此同时,新技术和平台的应用为 CAR T 疗法在非癌症病理中的应用提供了进一步的机会。在这里,我们回顾了 CAR T 疗法的基本原理、肿瘤学中面临的当前挑战、非癌症疾病初步报告的概述,以及对相关新兴技术的讨论。我们研究了这种疗法在广泛的背景下的潜在应用。最后,我们强调了对特异性和安全性的关注,并概述了 CAR T 疗法在癌症之外的发展方向。