适配器介导的嵌合抗原受体（CAR）的模块化 CAR-T 治疗的进展。
Advances in modular control of CAR-T therapy with adapter-mediated CARs.
机构信息
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA.
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
出版信息
Adv Drug Deliv Rev. 2022 Aug;187:114358. doi: 10.1016/j.addr.2022.114358. Epub 2022 May 23.
Protein engineering has contributed to successes in the field of T cell-based immunotherapy, including chimeric antigen receptor (CAR) T cell therapy. CAR T cell therapy has become a pillar of cancer immunotherapy, demonstrating clinical effectiveness against B cell malignancies by targeting the B cell antigen CD19. Current gene editing techniques have limited safety controls over CAR T cell activity, which presents a hurdle for control of CAR T cells in patients. Alternatively, CAR T cell activity can be controlled by engineering CARs to bind soluble adapter molecules that direct the interaction between the CAR T cell and target cell. The flexibility in this adapter-mediated approach overcomes the rigid specificity of traditional CAR T cells to allow targeting of multiple cell types. Here we describe adapter CAR T technologies and how these methods emphasize the growing role of protein engineering in the design of programmable tools for T cell therapies.
蛋白质工程在基于 T 细胞的免疫疗法领域取得了成功，包括嵌合抗原受体（CAR）T 细胞疗法。CAR T 细胞疗法已成为癌症免疫疗法的支柱，通过针对 B 细胞抗原 CD19 靶向治疗 B 细胞恶性肿瘤，显示出临床疗效。目前的基因编辑技术对 CAR T 细胞的活性缺乏安全控制，这对患者中 CAR T 细胞的控制构成了障碍。或者，可以通过设计 CAR 来结合可溶性衔接子分子来控制 CAR T 细胞的活性，这些衔接子分子指导 CAR T 细胞与靶细胞之间的相互作用。这种适配器介导方法的灵活性克服了传统 CAR T 细胞的刚性特异性，从而允许针对多种细胞类型进行靶向。在这里，我们描述了适配器 CAR T 技术，以及这些方法如何强调蛋白质工程在设计可编程 T 细胞治疗工具中的作用不断增强。
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