Joaquina Sandy, Forcados Christopher, Caulier Benjamin, Inderberg Else Marit, Wälchli Sébastien
Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway.
Center for Cancer Cell Reprogramming (CanCell), Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Front Bioeng Biotechnol. 2023 Jun 20;11:1207576. doi: 10.3389/fbioe.2023.1207576. eCollection 2023.
Adoptive transfer of T cells modified to express chimeric antigenic receptors (CAR) has emerged as a solution to cure refractory malignancies. However, although CAR T cell treatment of haematological cancers has now shown impressive improvement in outcome, solid tumours have been more challenging to control. The latter type is protected by a strong tumour microenvironment (TME) which might impact cellular therapeutic treatments. Indeed, the milieu around the tumour can become particularly inhibitory to T cells by directly affecting their metabolism. Consequently, the therapeutic cells become physically impeded before being able to attack the tumour. It is therefore extremely important to understand the mechanism behind this metabolic break in order to develop TME-resistant CAR T cells. Historically, the measurement of cellular metabolism has been performed at a low throughput which only permitted a limited number of measurements. However, this has been changed by the introduction of real-time technologies which have lately become more popular to study CAR T cell quality. Unfortunately, the published protocols lack uniformity and their interpretation become confusing. We herein tested the essential parameters to perform a metabolic study on CAR T cells and propose a check list of factors that should be set in order to draw sound conclusion.
采用经修饰以表达嵌合抗原受体（CAR）的T细胞进行过继性转移，已成为治愈难治性恶性肿瘤的一种解决方案。然而，尽管CAR-T细胞治疗血液系统癌症目前已在疗效上显示出令人瞩目的改善，但实体瘤的控制一直更具挑战性。后一种类型受到强大的肿瘤微环境（TME）的保护，这可能会影响细胞治疗。实际上，肿瘤周围的环境可能会通过直接影响T细胞的代谢而对其产生特别的抑制作用。因此，治疗性细胞在能够攻击肿瘤之前就会受到物理阻碍。因此，了解这种代谢中断背后的机制对于开发抗TME的CAR-T细胞极为重要。从历史上看，细胞代谢的测量一直以低通量进行，只能进行有限数量的测量。然而，实时技术的引入改变了这种情况，这些技术最近在研究CAR-T细胞质量方面变得更加流行。不幸的是，已发表的方案缺乏一致性，其解释也变得令人困惑。我们在此测试了对CAR-T细胞进行代谢研究的基本参数，并提出了一份为得出可靠结论而应设定的因素清单。
