Department of Pharmacy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, China.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guo Xue Xiang, Chengdu, 610041, China.
J Transl Med. 2024 May 1;22(1):413. doi: 10.1186/s12967-024-05206-7.
Adoptive cell therapy has revolutionized cancer treatment, especially for hematologic malignancies. T cells are the most extensively utilized cells in adoptive cell therapy. Currently, tumor-infiltrating lymphocytes, T cell receptor-transgenic T cells and chimeric antigen receptor T cells are the three main adoptive T cell therapies. Tumor-infiltrating lymphocytes kill tumors by reinfusing enlarged lymphocytes that naturally target tumor-specific antigens into the patient. T cell receptor-transgenic T cells have the ability to specifically destroy tumor cells via the precise recognition of exogenous T cell receptors with major histocompatibility complex. Chimeric antigen receptor T cells transfer genes with specific antigen recognition structural domains and T cell activation signals into T cells, allowing T cells to attack tumors without the assistance of major histocompatibility complex. Many barriers have been demonstrated to affect the clinical efficacy of adoptive T cell therapy, such as tumor heterogeneity and antigen loss, hard trafficking and infiltration, immunosuppressive tumor microenvironment and T cell exhaustion. Several strategies to improve the efficacy of adoptive T cell therapy have been explored, including multispecific chimeric antigen receptor T cell therapy, combination with immune checkpoint blockade, targeting the immunosuppressive tumor microenvironment, etc. In this review, we will summarize the current status and clinical application, followed by major bottlenecks in adoptive T cell therapy. In addition, we will discuss the promising strategies to improve adoptive T cell therapy. Adoptive T cell therapy will result in even more incredible advancements in solid tumors if the aforementioned problems can be handled.
过继细胞疗法革新了癌症治疗，尤其是血液系统恶性肿瘤的治疗。T 细胞是过继细胞疗法中应用最广泛的细胞。目前，过继 T 细胞治疗主要包括肿瘤浸润淋巴细胞、T 细胞受体转基因 T 细胞和嵌合抗原受体 T 细胞三种。肿瘤浸润淋巴细胞通过将自然靶向肿瘤特异性抗原的扩增淋巴细胞回输给患者来杀伤肿瘤。T 细胞受体转基因 T 细胞通过外源性 T 细胞受体与主要组织相容性复合体的精确识别，具有特异性杀伤肿瘤细胞的能力。嵌合抗原受体 T 细胞将具有特定抗原识别结构域和 T 细胞激活信号的基因转入 T 细胞，使 T 细胞能够在不依赖主要组织相容性复合体的情况下攻击肿瘤。有许多障碍被证明会影响过继 T 细胞疗法的临床疗效，如肿瘤异质性和抗原丢失、难以运输和浸润、免疫抑制性肿瘤微环境和 T 细胞耗竭等。为了提高过继 T 细胞疗法的疗效，已经探索了多种策略，包括多特异性嵌合抗原受体 T 细胞疗法、与免疫检查点阻断联合、靶向免疫抑制性肿瘤微环境等。在本文中，我们将总结过继 T 细胞疗法的现状和临床应用，以及过继 T 细胞疗法存在的主要瓶颈，并讨论改善过继 T 细胞疗法的有前景的策略。如果能够解决上述问题，过继 T 细胞疗法在实体瘤中的应用将会取得更加令人瞩目的进展。
