Department of General Surgery, Second Hospital of Lanzhou University, Lanzhou, China.
Key Laboratory of the Digestive System Tumors of Gansu Province, Second Hospital of Lanzhou University, Lanzhou, China.
Front Immunol. 2021 May 19;12:687822. doi: 10.3389/fimmu.2021.687822. eCollection 2021.
Chimeric antigen receptor (CAR) T-cell immunotherapy refers to an adoptive immunotherapy that has rapidly developed in recent years. It is a novel type of treatment that enables T cells to express specific CARs on their surface, then returns these T cells to tumor patients to kill the corresponding tumor cells. Significant strides in CAR-T cell immunotherapy against hematologic malignancies have elicited research interest among scholars in the treatment of solid tumors. Nonetheless, in contrast with the efficacy of CAR-T cell immunotherapy in the treatment of hematologic malignancies, its general efficacy against solid tumors is insignificant. This has been attributed to the complex biological characteristics of solid tumors. CAR-T cells play a better role in solid tumors, for instance by addressing obstacles including the lack of specific targets, inhibition of tumor microenvironment (TME), homing barriers of CAR-T cells, differentiation and depletion of CAR-T cells, inhibition of immune checkpoints, trogocytosis of CAR-T cells, tumor antigen heterogeneity, etc. This paper reviews the obstacles influencing the efficacy of CAR-T cell immunotherapy in solid tumors, their mechanism, and coping strategies, as well as economic restriction of CAR-T cell immunotherapy and its solutions. It aims to provide some references for researchers to better overcome the obstacles that affect the efficacy of CAR-T cells in solid tumors.
嵌合抗原受体 (CAR) T 细胞免疫疗法是近年来迅速发展起来的一种过继免疫疗法。它是一种新型的治疗方法,可以使 T 细胞在其表面表达特定的 CAR,然后将这些 T 细胞回输给肿瘤患者以杀死相应的肿瘤细胞。CAR-T 细胞免疫疗法在血液恶性肿瘤方面的显著进展引起了学者们对实体瘤治疗的研究兴趣。然而,与 CAR-T 细胞免疫疗法在血液恶性肿瘤治疗中的疗效相比,其对实体瘤的总体疗效并不显著。这归因于实体瘤复杂的生物学特性。CAR-T 细胞在实体瘤中发挥更好的作用,例如通过解决缺乏特定靶点、肿瘤微环境 (TME) 抑制、CAR-T 细胞归巢障碍、CAR-T 细胞分化和耗竭、免疫检查点抑制、CAR-T 细胞 trogocytosis、肿瘤抗原异质性等障碍。本文综述了影响 CAR-T 细胞免疫疗法在实体瘤中疗效的障碍及其机制和应对策略,以及 CAR-T 细胞免疫疗法的经济限制及其解决方案。旨在为研究人员提供一些参考,以更好地克服影响 CAR-T 细胞在实体瘤中疗效的障碍。
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