Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy at the University of Pennsylvania, Philadelphia, PA, USA; Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.
Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Parker Institute for Cancer Immunotherapy at the University of Pennsylvania, Philadelphia, PA, USA; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Trends Cancer. 2024 Aug;10(8):687-695. doi: 10.1016/j.trecan.2024.05.007. Epub 2024 Jun 8.
Chimeric antigen receptor (CAR) T cell therapy has emerged as a revolutionary treatment for hematological malignancies, but its adaptation to solid tumors is impeded by multiple challenges, particularly T cell dysfunction and exhaustion. The heterogeneity and inhospitableness of the solid tumor microenvironment (TME) contribute to diminished CAR T cell efficacy exhibited by reduced cytotoxicity, proliferation, cytokine secretion, and the upregulation of inhibitory receptors, similar to the phenotype of tumor-infiltrating lymphocytes (TILs). In this review, we highlight recent advances in T cell therapy for solid tumors, particularly brain cancer. Innovative strategies, including locoregional delivery and 'armoring' CAR T cells with cytokines such as interleukin (IL)-18, are under investigation to improve efficacy and safety. We also highlight emerging issues with toxicity management of CAR T cell adverse events. This review discusses the obstacles associated with CAR T cell therapy in the context of solid tumors and outlines current and future strategies to overcome these challenges.
嵌合抗原受体 (CAR) T 细胞疗法已成为血液恶性肿瘤的一种革命性治疗方法,但由于多种挑战,包括 T 细胞功能障碍和衰竭,其在实体瘤中的应用受到阻碍。实体瘤微环境 (TME) 的异质性和不适合性导致 CAR T 细胞的功效降低,表现为细胞毒性、增殖、细胞因子分泌和抑制性受体的上调减少,类似于肿瘤浸润淋巴细胞 (TILs) 的表型。在这篇综述中,我们重点介绍了用于实体瘤,特别是脑癌的 T 细胞治疗的最新进展。正在研究创新策略,包括局部递送和用白细胞介素 (IL)-18 等细胞因子“武装”CAR T 细胞,以提高疗效和安全性。我们还强调了 CAR T 细胞不良事件毒性管理方面的新问题。这篇综述讨论了与实体瘤中 CAR T 细胞治疗相关的障碍,并概述了克服这些挑战的当前和未来策略。
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