Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)-T Cells.
Ali Hosseini Rad S MJoshua Colin HalpinMojtaba MollaeiSamuel W J Smith BellNattiya HirankarnAlexander D McLellanPublished in: Cancers (2021)
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.
Keyphrases
- cell therapy
- stem cells
- oxidative stress
- mesenchymal stem cells
- end stage renal disease
- primary care
- chronic kidney disease
- low dose
- newly diagnosed
- rheumatoid arthritis
- type diabetes
- physical activity
- risk assessment
- metabolic syndrome
- cell death
- combination therapy
- systemic lupus erythematosus
- insulin resistance
- smoking cessation
- patient reported
- human health