Zheng Zhibo, Li Siyuan, Liu Mohan, Chen Chuyan, Zhang Lu, Zhou Daobin
Department of International Medical Services, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Department of Hematology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Cancers (Basel). 2023 Jul 3;15(13):3476. doi: 10.3390/cancers15133476.
Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target multiple antigens and overcome individual limitations. Despite these advancements, some shortcomings prevent the widespread use of CAR-T therapy, including life-threatening toxicities, T-cell exhaustion, and inadequate infiltration for solid tumors. Researchers have made considerable efforts to address these issues by developing new strategies for improving CAR-T cell function and reducing toxicities. This review provides an overview of the path of CAR-T cell development and highlights some of the prominent advances in its structure and manufacturing process, which include the strategies to improve antigen recognition, enhance T-cell activation and persistence, and overcome immune escape. Finally, the review briefly covers other immune cells for cancer therapy and ends with the discussion on the broad prospects of CAR-T in the treatment of various diseases, not just hematological tumors, and the challenges that need to be addressed for the widespread clinical application of CAR-T cell therapies.
嵌合抗原受体（CAR）-T细胞疗法是一种很有前景的免疫疗法，在过去几十年里取得了重大进展。它涉及对T细胞进行基因改造，使其靶向表达特定抗原的癌细胞，为治疗各种类型的癌症提供了一种新方法。然而，由于增殖不足和不良后果，第一代CAR-T细胞的初步成功受到限制。尽管如此，CAR-T细胞工程已经取得了重大进展，导致了最新的第五代CAR-T细胞的开发，这种细胞可以靶向多种抗原并克服个体局限性。尽管有这些进展，但一些缺点阻碍了CAR-T疗法的广泛应用，包括危及生命的毒性、T细胞耗竭以及实体瘤浸润不足。研究人员通过开发改善CAR-T细胞功能和降低毒性的新策略，为解决这些问题做出了相当大的努力。本综述概述了CAR-T细胞的发展历程，并重点介绍了其结构和制造过程中的一些突出进展，包括改善抗原识别、增强T细胞活化和持久性以及克服免疫逃逸的策略。最后，综述简要介绍了用于癌症治疗的其他免疫细胞，并以讨论CAR-T在治疗各种疾病（不仅是血液肿瘤）方面的广阔前景以及CAR-T细胞疗法广泛临床应用需要解决的挑战作为结尾。
