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Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes

Genetically engineered chimeric antigen receptor (CAR) T cells can cure patients with cancers that are refractory to standard therapeutic approaches. To date, adoptive cell therapies have been less effective against solid tumors, largely due to impaired homing and function of immune cells within the...

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Autores principales: Nanjireddy, Priyanka Maridhi, Olejniczak, Scott H., Buxbaum, Nataliya Prokopenko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043186/
https://www.ncbi.nlm.nih.gov/pubmed/36999013
http://dx.doi.org/10.3389/fimmu.2023.1121565
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author Nanjireddy, Priyanka Maridhi
Olejniczak, Scott H.
Buxbaum, Nataliya Prokopenko
author_facet Nanjireddy, Priyanka Maridhi
Olejniczak, Scott H.
Buxbaum, Nataliya Prokopenko
author_sort Nanjireddy, Priyanka Maridhi
collection PubMed
description Genetically engineered chimeric antigen receptor (CAR) T cells can cure patients with cancers that are refractory to standard therapeutic approaches. To date, adoptive cell therapies have been less effective against solid tumors, largely due to impaired homing and function of immune cells within the immunosuppressive tumor microenvironment (TME). Cellular metabolism plays a key role in T cell function and survival and is amenable to manipulation. This manuscript provides an overview of known aspects of CAR T metabolism and describes potential approaches to manipulate metabolic features of CAR T to yield better anti-tumor responses. Distinct T cell phenotypes that are linked to cellular metabolism profiles are associated with improved anti-tumor responses. Several steps within the CAR T manufacture process are amenable to interventions that can generate and maintain favorable intracellular metabolism phenotypes. For example, co-stimulatory signaling is executed through metabolic rewiring. Use of metabolic regulators during CAR T expansion or systemically in the patient following adoptive transfer are described as potential approaches to generate and maintain metabolic states that can confer improved in vivo T cell function and persistence. Cytokine and nutrient selection during the expansion process can be tailored to yield CAR T products with more favorable metabolic features. In summary, improved understanding of CAR T cellular metabolism and its manipulations have the potential to guide the development of more effective adoptive cell therapies.
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spelling pubmed-100431862023-03-29 Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes Nanjireddy, Priyanka Maridhi Olejniczak, Scott H. Buxbaum, Nataliya Prokopenko Front Immunol Immunology Genetically engineered chimeric antigen receptor (CAR) T cells can cure patients with cancers that are refractory to standard therapeutic approaches. To date, adoptive cell therapies have been less effective against solid tumors, largely due to impaired homing and function of immune cells within the immunosuppressive tumor microenvironment (TME). Cellular metabolism plays a key role in T cell function and survival and is amenable to manipulation. This manuscript provides an overview of known aspects of CAR T metabolism and describes potential approaches to manipulate metabolic features of CAR T to yield better anti-tumor responses. Distinct T cell phenotypes that are linked to cellular metabolism profiles are associated with improved anti-tumor responses. Several steps within the CAR T manufacture process are amenable to interventions that can generate and maintain favorable intracellular metabolism phenotypes. For example, co-stimulatory signaling is executed through metabolic rewiring. Use of metabolic regulators during CAR T expansion or systemically in the patient following adoptive transfer are described as potential approaches to generate and maintain metabolic states that can confer improved in vivo T cell function and persistence. Cytokine and nutrient selection during the expansion process can be tailored to yield CAR T products with more favorable metabolic features. In summary, improved understanding of CAR T cellular metabolism and its manipulations have the potential to guide the development of more effective adoptive cell therapies. Frontiers Media S.A. 2023-03-14 /pmc/articles/PMC10043186/ /pubmed/36999013 http://dx.doi.org/10.3389/fimmu.2023.1121565 Text en Copyright © 2023 Nanjireddy, Olejniczak and Buxbaum https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Nanjireddy, Priyanka Maridhi
Olejniczak, Scott H.
Buxbaum, Nataliya Prokopenko
Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
title Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
title_full Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
title_fullStr Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
title_full_unstemmed Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
title_short Targeting of chimeric antigen receptor T cell metabolism to improve therapeutic outcomes
title_sort targeting of chimeric antigen receptor t cell metabolism to improve therapeutic outcomes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10043186/
https://www.ncbi.nlm.nih.gov/pubmed/36999013
http://dx.doi.org/10.3389/fimmu.2023.1121565
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