表达嵌合抗原受体 (CAR) 的工程化 T 细胞已经改变了血液癌症的治疗方法。 CAR 将抗体的肿瘤抗原结合功能与 T 细胞受体 (TCR) δ 链和共刺激受体的信号传导功能结合起来。由此产生的构建体旨在模拟 T 细胞基于 TCR 和共受体的激活。尽管这些药物已成功治疗某些类型的癌症，但仍需要新的 CAR 形式，以限制副作用并将其用途扩大到实体癌。对 TCR 信号传导机制的深入了解，包括识别 TCR δ 链中不存在的信号基序以及 TCR 激活的机制见解，使得 CAR 格式的开发能够在临床前小鼠模型和临床试验中超越当前的 CAR。在本视角中，我们探讨了新 CAR 设计背后的机械原理。© 2024。Springer Nature Limited。

Engineered T cells that express chimeric antigen receptors (CARs) have transformed the treatment of haematological cancers. CARs combine the tumour-antigen-binding function of antibodies with the signalling functions of the T-= cell receptor (TCR) ζ chain and co-stimulatory receptors. The resulting constructs aim to mimic the TCR-based and co-receptor-based activation of T cells. Although these have been successful for some types of cancer, new CAR formats are needed, to limit side effects and broaden their use to solid cancers. Insights into the mechanisms of TCR signalling, including the identification of signalling motifs that are not present in the TCR ζ chain and mechanistic insights in TCR activation, have enabled the development of CAR formats that outcompete the current CARs in preclinical mouse models and clinical trials. In this Perspective, we explore the mechanistic rationale behind new CAR designs.© 2024. Springer Nature Limited.