Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, 0379 Oslo, Norway.
Center for Cancer Cell Reprogramming (CanCell), Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway.
Cells. 2022 Apr 25;11(9):1454. doi: 10.3390/cells11091454.
The manufacture of efficacious CAR T cells represents a major challenge in cellular therapy. An important aspect of their quality concerns energy production and consumption, known as metabolism. T cells tend to adopt diverse metabolic profiles depending on their differentiation state and their stimulation level. It is therefore expected that the introduction of a synthetic molecule such as CAR, activating endogenous signaling pathways, will affect metabolism. In addition, upon patient treatment, the tumor microenvironment might influence the CAR T cell metabolism by compromising the energy resources. The access to novel technology with higher throughput and reduced cost has led to an increased interest in studying metabolism. Indeed, methods to quantify glycolysis and mitochondrial respiration have been available for decades but were rarely applied in the context of CAR T cell therapy before the release of the Seahorse XF apparatus. The present review will focus on the use of this instrument in the context of studies describing the impact of CAR on T cell metabolism and the strategies to render of CAR T cells more metabolically fit.
高效的 CAR T 细胞的制造是细胞治疗中的一个主要挑战。其质量的一个重要方面涉及到能量的产生和消耗，也就是代谢。T 细胞往往根据其分化状态和刺激水平采用不同的代谢特征。因此，可以预期，引入 CAR 等合成分子，激活内源性信号通路，将影响代谢。此外，在对患者进行治疗时，肿瘤微环境可能会通过耗尽能量资源来影响 CAR T 细胞的代谢。新型技术具有更高的通量和更低的成本，这使得人们对代谢研究产生了更大的兴趣。事实上，几十年来，定量检测糖酵解和线粒体呼吸的方法已经存在，但在 Seahorse XF 仪器问世之前，很少将这些方法应用于 CAR T 细胞治疗的背景下。本综述将重点介绍该仪器在描述 CAR 对 T 细胞代谢影响以及使 CAR T 细胞更适应代谢的策略方面的应用。
