Cargando…
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...
Autores principales: | , , |
---|---|
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 |
_version_ | 1784913087673925632 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10043186 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT nanjireddypriyankamaridhi targetingofchimericantigenreceptortcellmetabolismtoimprovetherapeuticoutcomes AT olejniczakscotth targetingofchimericantigenreceptortcellmetabolismtoimprovetherapeuticoutcomes AT buxbaumnataliyaprokopenko targetingofchimericantigenreceptortcellmetabolismtoimprovetherapeuticoutcomes |