CAR-T 细胞在实体瘤微环境中的行进。
Navigating CAR-T cells through the solid-tumour microenvironment.
机构信息
Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, USA.
出版信息
Nat Rev Drug Discov. 2021 Jul;20(7):531-550. doi: 10.1038/s41573-021-00189-2. Epub 2021 May 10.
The adoptive transfer of T cells that are engineered to express chimeric antigen receptors (CARs) has shown remarkable success in treating B cell malignancies but only limited efficacy against other cancer types, especially solid tumours. Compared with haematological diseases, solid tumours present a unique set of challenges, including a lack of robustly expressed, tumour-exclusive antigen targets as well as highly immunosuppressive and metabolically challenging tumour microenvironments that limit treatment safety and efficacy. Here, we review protein- and cell-engineering strategies that seek to overcome these obstacles and produce next-generation T cells with enhanced tumour specificity and sustained effector function for the treatment of solid malignancies.
嵌合抗原受体 (CAR) 修饰的 T 细胞过继转移在治疗 B 细胞恶性肿瘤方面取得了显著成功，但对其他癌症类型，特别是实体瘤的疗效有限。与血液系统疾病相比，实体瘤存在一系列独特的挑战，包括缺乏强有力表达的、肿瘤特有的抗原靶点，以及高度免疫抑制和代谢挑战性的肿瘤微环境，这限制了治疗的安全性和疗效。在这里，我们综述了旨在克服这些障碍的蛋白质和细胞工程策略，以产生具有增强的肿瘤特异性和持续的效应功能的新一代 T 细胞，用于治疗实体恶性肿瘤。
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