Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells

Cancers

Mojtaba Mollaei¹  Samuel W. J. Smith Bell²  Alexander D. McLellan²  Ali Hosseini Rad S. M.²  Joshua Colin Halpin²  Nattiya Hirankarn³ 

[1] Department of Immunology, School of Medicine, Tarbiat Modares University, Tehran 14117-13116, Iran;Department of Microbiology and Immunology, University of Otago, Dunedin 9010, Otago, New Zealand;Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;

关键词: CAR T cell therapy;    T cell metabolism;    mitochondria;    memory T cell;    metabolic reprogramming;   

DOI  :  10.3390/cancers13061229

来源: DOAJ

【 摘 要 】

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized adoptive cell therapy with impressive therapeutic outcomes of 80% complete remission (CR) rates in some haematological malignancies. Despite this, CAR T cell therapy for the treatment of solid tumours has invariably been unsuccessful in the clinic. Immunosuppressive factors and metabolic stresses in the tumour microenvironment (TME) result in the dysfunction and exhaustion of CAR T cells. A growing body of evidence demonstrates the importance of the mitochondrial and metabolic state of CAR T cells prior to infusion into patients. The different T cell subtypes utilise distinct metabolic pathways to fulfil their energy demands associated with their function. The reprogramming of CAR T cell metabolism is a viable approach to manufacture CAR T cells with superior antitumour functions and increased longevity, whilst also facilitating their adaptation to the nutrient restricted TME. This review discusses the mitochondrial and metabolic state of T cells, and describes the potential of the latest metabolic interventions to maximise CAR T cell efficacy for solid tumours.

【 授权许可】

Unknown