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

SIMPLE SUMMARY: We review the mechanisms of cellular metabolism and mitochondrial function that have potential to impact on the success of chimeric antigen receptor (CAR) T cell therapy. The review focuses readers on mitochondrial functions to allow a better understanding of the complexity of T cell...

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Autores principales: Rad S. M., Ali Hosseini, Halpin, Joshua Colin, Mollaei, Mojtaba, Smith Bell, Samuel W. J., Hirankarn, Nattiya, McLellan, Alexander D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002030/
https://www.ncbi.nlm.nih.gov/pubmed/33799768
http://dx.doi.org/10.3390/cancers13061229
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author Rad S. M., Ali Hosseini
Halpin, Joshua Colin
Mollaei, Mojtaba
Smith Bell, Samuel W. J.
Hirankarn, Nattiya
McLellan, Alexander D.
author_facet Rad S. M., Ali Hosseini
Halpin, Joshua Colin
Mollaei, Mojtaba
Smith Bell, Samuel W. J.
Hirankarn, Nattiya
McLellan, Alexander D.
author_sort Rad S. M., Ali Hosseini
collection PubMed
description SIMPLE SUMMARY: We review the mechanisms of cellular metabolism and mitochondrial function that have potential to impact on the success of chimeric antigen receptor (CAR) T cell therapy. The review focuses readers on mitochondrial functions to allow a better understanding of the complexity of T cell metabolic pathways, energetics and apoptotic/antiapoptotic pathways occurring in CAR T cells. We highlight potential modifications of T cell metabolism and mitochondrial function for the benefit of improved adoptive cellular therapy. Reprogramming metabolism in CAR T cells is an attractive approach to improve antitumour functions, increase persistence and enable adaptation to the nutrient-restricted solid tumour environment. ABSTRACT: 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.
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spelling pubmed-80020302021-03-28 Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells Rad S. M., Ali Hosseini Halpin, Joshua Colin Mollaei, Mojtaba Smith Bell, Samuel W. J. Hirankarn, Nattiya McLellan, Alexander D. Cancers (Basel) Review SIMPLE SUMMARY: We review the mechanisms of cellular metabolism and mitochondrial function that have potential to impact on the success of chimeric antigen receptor (CAR) T cell therapy. The review focuses readers on mitochondrial functions to allow a better understanding of the complexity of T cell metabolic pathways, energetics and apoptotic/antiapoptotic pathways occurring in CAR T cells. We highlight potential modifications of T cell metabolism and mitochondrial function for the benefit of improved adoptive cellular therapy. Reprogramming metabolism in CAR T cells is an attractive approach to improve antitumour functions, increase persistence and enable adaptation to the nutrient-restricted solid tumour environment. ABSTRACT: 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. MDPI 2021-03-11 /pmc/articles/PMC8002030/ /pubmed/33799768 http://dx.doi.org/10.3390/cancers13061229 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Rad S. M., Ali Hosseini
Halpin, Joshua Colin
Mollaei, Mojtaba
Smith Bell, Samuel W. J.
Hirankarn, Nattiya
McLellan, Alexander D.
Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells
title Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells
title_full Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells
title_fullStr Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells
title_full_unstemmed Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells
title_short Metabolic and Mitochondrial Functioning in Chimeric Antigen Receptor (CAR)—T Cells
title_sort metabolic and mitochondrial functioning in chimeric antigen receptor (car)—t cells
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002030/
https://www.ncbi.nlm.nih.gov/pubmed/33799768
http://dx.doi.org/10.3390/cancers13061229
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