Cancer Institute, the First Clinical Medical College, Xuzhou Medical University, Xuzhou, Jiangsu, China; Center of Clinical Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China; Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Biochem Pharmacol. 2024 Sep;227:116439. doi: 10.1016/j.bcp.2024.116439. Epub 2024 Jul 18.
Chimeric antigen receptor (CAR)-engineered T cells have been defined as 'living drug'. Adding a co-stimulatory domain (CSD) has enhanced the anti-hematological effects of CAR-T cells, thereby elevating their viability for medicinal applications. Various CSDs have helped prepare CAR-T cells to study anti-tumor efficacy. Previous studies have described and summarized the anti-tumor efficacy of CAR-T cells obtained from different CSDs. However, the underlying molecular mechanisms by which different CSDs affect CAR-T function have been rarely reported. The role of CSDs in T cells has been significantly studied, but whether they can play a unique role as a part of the CAR structure remains undetermined. Here, we summarized the effects of CSDs on CAR-T signaling pathways based on the limited references and speculated the possible mechanism depending on the specific characteristics of CAR-T cells. This review will help understand the molecular mechanism of CSDs in CAR-T cells that exert different anti-tumor effects while providing potential guidance for further interventions to enhance anti-tumor efficacy in immunotherapy.
嵌合抗原受体 (CAR)-修饰的 T 细胞已被定义为“活药物”。添加共刺激结构域 (CSD) 增强了 CAR-T 细胞的抗血液肿瘤作用，从而提高了其在医学应用中的活力。各种 CSD 有助于制备 CAR-T 细胞以研究抗肿瘤功效。先前的研究已经描述和总结了来自不同 CSD 的 CAR-T 细胞的抗肿瘤功效。然而，不同 CSD 影响 CAR-T 功能的潜在分子机制很少有报道。CSD 在 T 细胞中的作用已经得到了充分的研究，但它们是否可以作为 CAR 结构的一部分发挥独特的作用仍不确定。在这里，我们根据有限的参考文献总结了 CSD 对 CAR-T 信号通路的影响，并根据 CAR-T 细胞的具体特征推测了可能的机制。本综述将有助于了解 CSD 在 CAR-T 细胞中发挥不同抗肿瘤作用的分子机制，同时为进一步干预以增强免疫疗法中的抗肿瘤疗效提供潜在指导。
