School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Shanghai Clinical Research and Trial Center, Shanghai, China.
Immunol Rev. 2023 Nov;320(1):138-146. doi: 10.1111/imr.13232. Epub 2023 Jun 27.
Chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising approach for cancer treatment. CAR is a synthetic immune receptor that recognizes tumor antigen and activates T cells through multiple signaling pathways. However, the current CAR design is not as robust as T cell receptor (TCR), a natural antigen receptor with high sensitivity and efficiency. TCR signaling relies on specific molecular interactions, and thus electrostatic force, the major force of molecular interactions, play critical roles. Understanding how electrostatic charge regulates TCR/CAR signaling events will facilitate the development of next-generation T cell therapies. This review summarizes recent findings on the roles of electrostatic interactions in both natural and synthetic immune receptor signaling, specifically that in CAR clustering and effector molecule recruitments, and highlights potential strategies for engineering CAR-T cell therapy by leveraging charge-based interactions.
嵌合抗原受体 (CAR)-T 细胞疗法已成为癌症治疗的一种有前途的方法。CAR 是一种合成免疫受体，通过多种信号通路识别肿瘤抗原并激活 T 细胞。然而，目前的 CAR 设计不如 T 细胞受体 (TCR) 那样强大，TCR 是一种具有高灵敏度和高效率的天然抗原受体。TCR 信号依赖于特定的分子相互作用，因此静电力作为分子相互作用的主要力，起着至关重要的作用。了解静电电荷如何调节 TCR/CAR 信号事件将有助于开发下一代 T 细胞疗法。本综述总结了最近关于静电相互作用在天然和合成免疫受体信号中的作用的发现，特别是在 CAR 聚集和效应分子募集中的作用，并强调了通过利用基于电荷的相互作用来设计 CAR-T 细胞疗法的潜在策略。
