Department of Pathology and Laboratory Medicine and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; email:
Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:805-829. doi: 10.1146/annurev-pharmtox-031720-102211. Epub 2020 Oct 9.
Cell-based immunotherapies using T cells that are engineered to express a chimeric antigen receptor (CAR-T cells) are an effective treatment option for several B cell malignancies. Compared with most drugs, CAR-T cell products are highly complex, as each cell product is composed of a heterogeneous mixture of millions of cells. The biodistribution and kinetics of CAR-T cells, following administration, are unique given the ability of T cells to actively migrate as well as replicate within the patient. CAR-T cell therapies also have multiple mechanisms of action that contribute to both their antitumor activity and their toxicity. This review provides an overview of the unique pharmacology of CAR-T cells, with a focus on CD19-targeting and B cell maturation antigen (BCMA)-targeting CAR-T cells.
基于细胞的免疫疗法利用经过基因工程改造表达嵌合抗原受体 (CAR-T 细胞) 的 T 细胞,是几种 B 细胞恶性肿瘤的有效治疗选择。与大多数药物相比,CAR-T 细胞产品非常复杂,因为每个细胞产品都是由数百万个细胞组成的异质混合物。鉴于 T 细胞能够在患者体内主动迁移和复制,CAR-T 细胞给药后的分布和动力学是独特的。CAR-T 细胞疗法还具有多种作用机制,这些机制有助于其抗肿瘤活性和毒性。本文综述了 CAR-T 细胞的独特药理学,重点介绍了针对 CD19 和 B 细胞成熟抗原 (BCMA) 的 CAR-T 细胞。