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嵌合抗原受体 T 细胞疗法在实体瘤治疗中的进展。

Advances in Chimeric Antigen Receptor T-Cell Therapies for Solid Tumors.

机构信息

Department of Pharmacology and Experimental Therapeutics, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

出版信息

Clin Pharmacol Ther. 2019 Jan;105(1):71-78. doi: 10.1002/cpt.1280.

Abstract

In 2017, the US Food and Drug Administration approved the first two novel cellular immunotherapies using synthetic, engineered receptors known as chimeric antigen receptors (CARs), tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), expressed by patient-derived T cells for the treatment of hematological malignancies expressing the B-cell surface antigen CD19 in both pediatric and adult patients. This approval marked a major milestone in the use of antigen-directed "living drugs" for the treatment of relapsed or refractory blood cancers, and with these two approvals, there is increased impetus to expand not only the target antigens but also the tumor types that can be targeted. This state-of-the-art review will focus on the challenges, advances, and novel approaches being used to implement CAR T-cell immunotherapy for the treatment of solid tumors.

摘要

2017 年,美国食品和药物管理局批准了两种新型细胞免疫疗法,这两种疗法使用的是合成的、经过工程改造的受体,称为嵌合抗原受体(CAR),即由患者来源的 T 细胞表达的 tisagenlecleucel(Kymriah)和 axicabtagene ciloleucel(Yescarta),用于治疗在儿科和成年患者中表达 B 细胞表面抗原 CD19 的血液恶性肿瘤。这一批准标志着抗原导向的“活药物”治疗复发或难治性血癌的一个重大里程碑,随着这两种批准,不仅扩大了目标抗原,而且扩大了可以靶向的肿瘤类型的动力也有所增加。本综述将重点介绍为治疗实体瘤而实施 CAR T 细胞免疫疗法所面临的挑战、进展和新方法。

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