Determination of CAR T cell metabolism in an optimized protocol

Frontiers in Bioengineering and Biotechnology

Bioengineering and Biotechnology

Else Marit Inderberg¹  Sandy Joaquina¹  Christopher Forcados¹  Sébastien Wälchli¹  Benjamin Caulier² 

[1] Translational Research Unit, Department of Cellular Therapy, Oslo University Hospital, Oslo, Norway;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;Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, Oslo, Norway;

关键词: CAR T cell;    Seahorse XF96;    metabolim;    immunotherapy;    cancer therapy;   

DOI  :  10.3389/fbioe.2023.1207576

 received in 2023-04-17, accepted in 2023-06-12,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Joaquina, Forcados, Caulier, Inderberg and Wälchli.