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嵌合抗原受体 T 细胞疗法治疗胶质母细胞瘤:最新临床进展与未来挑战。

CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges.

机构信息

Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

Center for Cellular Immunotherapies, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

出版信息

Neuro Oncol. 2018 Oct 9;20(11):1429-1438. doi: 10.1093/neuonc/noy032.

Abstract

In patients with certain hematologic malignancies, the use of autologous T cells genetically modified to express chimeric antigen receptors (CARs) has led to unprecedented clinical responses. Although progress in solid tumors has been elusive, recent clinical studies have demonstrated the feasibility and safety of CAR T-cell therapy for glioblastoma. In addition, despite formidable barriers to T-cell localization and effector function in glioblastoma, signs of efficacy have been observed in select patients. In this review, we begin with a discussion of established obstacles to systemic therapy in glioblastoma and how these may be overcome by CAR T cells. We continue with a summary of previously published CAR T-cell trials in GBM, and end by outlining the key therapeutic challenges associated with the use of CAR T cells in this disease.

摘要

在某些血液恶性肿瘤患者中,使用经基因修饰表达嵌合抗原受体(CAR)的自体 T 细胞已带来前所未有的临床反应。尽管实体肿瘤方面的进展仍难以捉摸,但最近的临床研究表明 CAR T 细胞疗法治疗胶质母细胞瘤是可行且安全的。此外,尽管 CAR T 细胞在胶质母细胞瘤中存在定位和效应功能的巨大障碍,但在一些患者中观察到了疗效的迹象。在这篇综述中,我们首先讨论了胶质母细胞瘤全身治疗中存在的既定障碍,以及 CAR T 细胞如何克服这些障碍。然后我们总结了之前发表的 CAR T 细胞治疗胶质母细胞瘤的临床试验,并最后概述了在该疾病中使用 CAR T 细胞相关的关键治疗挑战。

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