Nature Reviews Clinical Oncology ( IF 81.1 ) Pub Date : 2024-11-15 , DOI: 10.1038/s41571-024-00959-y Caroline Diorio, David T. Teachey, Stephan A. Grupp
Chimeric antigen receptor (CAR) T cells are revolutionizing cancer therapy, particularly for haematological malignancies, conferring durable and sometimes curative responses in patients with advanced-stage disease. The CAR T cell products currently approved for clinical use are all autologous and are often effective; however, in patients who are lymphopenic and/or heavily pretreated with chemotherapy, autologous T cells can be difficult to harvest in sufficient numbers or have functional impairments that might ultimately render them less efficacious. Moreover, autologous products take several weeks to produce, and each product can be used in only one patient. By contrast, allogeneic CAR T cells can be produced for many patients using T cells from a single healthy donor, can be optimized for safety and efficacy, can be instantly available for ‘off-the-shelf’ use and, therefore, might also be more cost-effective. Despite these potential advantages, the development of allogeneic CAR T cells has lagged behind that of autologous products, owing to the additional challenges such as avoiding graft-versus-host disease and host-mediated graft rejection. Over the past few years, the development of advanced genome-editing techniques has facilitated the generation of novel allogeneic CAR T cell products. Furthermore, CAR cell products derived from other cell types such as induced pluripotent stem cells and natural killer cells are being investigated for clinical use. In this Review, we discuss the potential of allogeneic CAR cell products to expand life-saving immunotherapy to a much broader population of patients in the coming years, the progress made to date and strategies to overcome remaining hurdles.
中文翻译:
用于癌症的同种异体嵌合抗原受体细胞疗法:取得的进展和仍然存在的障碍
嵌合抗原受体 (CAR) T 细胞正在彻底改变癌症治疗,特别是对于血液系统恶性肿瘤,为晚期疾病患者提供持久的、有时是治愈性的反应。目前批准用于临床的 CAR T 细胞产品都是自体的,并且通常有效;然而,在淋巴细胞减少和/或接受过大量化疗的患者中,自体 T 细胞可能难以采集足够数量的 T 细胞或存在功能障碍,最终可能使其疗效降低。此外,自体产品需要数周时间才能生产,并且每种产品只能用于一名患者。相比之下,可以使用来自单个健康供体的 T 细胞为许多患者生产同种异体 CAR T 细胞,可以优化安全性和有效性,可以立即用于“现成”使用,因此也可能更具成本效益。尽管有这些潜在优势,但由于避免移植物抗宿主病和宿主介导的移植物排斥等额外挑战,同种异体 CAR T 细胞的开发落后于自体产品。在过去的几年里,先进的基因组编辑技术的发展促进了新型同种异体 CAR T 细胞产品的产生。此外,来自其他细胞类型(如诱导多能干细胞和自然杀伤细胞)的 CAR 细胞产品正在研究中用于临床。在这篇综述中,我们讨论了同种异体 CAR 细胞产品在未来几年将拯救生命的免疫疗法扩展到更广泛的患者群体的潜力、迄今为止取得的进展以及克服剩余障碍的策略。