Chimeric antigen receptor (CAR) T cells are an engineered immunotherapy that express synthetic receptors to recognize and kill cancer cells. Despite their success in treating hematologic cancers, CAR T cells have limited efficacy against solid tumors, in part due to the altered immunometabolic profile within the tumor environment, which hinders T cell proliferation, infiltration, and anti-tumor activity. For instance, CAR T cells must compete for essential nutrients within tumors, while resisting the impacts of immunosuppressive metabolic byproducts. In this review, we will describe the altered metabolic features within solid tumors that contribute to immunosuppression of CAR T cells. We'll discuss how overexpression of key metabolic enzymes can enhance the ability of CAR T cells to resist corresponding tumoral metabolic changes or even revert the metabolic profile of a tumor to a less inhibitory state. In addition, metabolic remodeling is intrinsically linked to T cell activity, differentiation, and function, such that metabolic engineering strategies can also promote establishment of more or less efficacious CAR T cell phenotypes. Overall, we will show how applying metabolic engineering strategies holds significant promise in improving CAR T cells for the treatment of solid tumors.

中文翻译：

---

将代谢控制策略应用于工程化 T 细胞癌治疗


嵌合抗原受体 （CAR） T 细胞是一种工程化免疫疗法，可表达合成受体以识别和杀死癌细胞。尽管 CAR T 细胞在治疗血液系统癌症方面取得了成功，但 CAR T 细胞对实体瘤的疗效有限，部分原因是肿瘤环境中免疫代谢谱的改变阻碍了 T 细胞增殖、浸润和抗肿瘤活性。例如，CAR T 细胞必须在肿瘤内竞争必需的营养物质，同时抵抗免疫抑制代谢副产物的影响。在这篇综述中，我们将描述实体瘤内导致 CAR T 细胞免疫抑制的改变代谢特征。我们将讨论关键代谢酶的过表达如何增强 CAR T 细胞抵抗相应肿瘤代谢变化的能力，甚至将肿瘤的代谢特征恢复到抑制性较低的状态。此外，代谢重塑与 T 细胞活性、分化和功能有着内在的联系，因此代谢工程策略也可以促进或多或少有效的 CAR T 细胞表型的建立。总体而言，我们将展示应用代谢工程策略如何在改善 CAR T 细胞治疗实体瘤方面具有重要前景。