Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Department of Chemical and Biomolecular Engineering, University of California-Los Angeles, Los Angeles, CA 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California-Los Angeles, Los Angeles, CA 90095, USA; Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, CA 90095, USA.
Cancer Cell. 2020 Oct 12;38(4):473-488. doi: 10.1016/j.ccell.2020.07.005. Epub 2020 Jul 30.
T cells engineered to express chimeric antigen receptors (CARs) with tumor specificity have shown remarkable success in treating patients with hematologic malignancies and revitalized the field of adoptive cell therapy. However, realizing broader therapeutic applications of CAR-T cells necessitates engineering approaches on multiple levels to enhance efficacy and safety. Particularly, solid tumors present unique challenges due to the biological complexity of the solid-tumor microenvironment (TME). In this review, we highlight recent strategies to improve CAR-T cell therapy by engineering (1) the CAR protein, (2) T cells, and (3) the interaction between T cells and other components in the TME.
经基因工程改造表达肿瘤特异性嵌合抗原受体 (CAR) 的 T 细胞在治疗血液系统恶性肿瘤患者方面取得了显著成功，使过继细胞治疗领域重获生机。然而，要将 CAR-T 细胞更广泛地应用于治疗，就需要在多个层面上采用工程化方法来提高疗效和安全性。特别是，由于实体瘤微环境 (TME) 的生物学复杂性，实体瘤带来了独特的挑战。在这篇综述中，我们重点介绍了通过工程化 (1) CAR 蛋白、(2) T 细胞和 (3) T 细胞与 TME 中其他成分之间的相互作用来改进 CAR-T 细胞治疗的最新策略。
