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Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies
Over the past 20 years natural killer (NK) cell-based immunotherapies have emerged as a safe and effective treatment option for patients with relapsed or refractory leukemia. Unlike T cell-based therapies, NK cells harbor an innate capacity to eliminate malignant cells without prior sensitization an...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578927/ https://www.ncbi.nlm.nih.gov/pubmed/34777383 http://dx.doi.org/10.3389/fimmu.2021.765705 |
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author | Barnes, Samantha A. Trew, Isabella de Jong, Emma Foley, Bree |
author_facet | Barnes, Samantha A. Trew, Isabella de Jong, Emma Foley, Bree |
author_sort | Barnes, Samantha A. |
collection | PubMed |
description | Over the past 20 years natural killer (NK) cell-based immunotherapies have emerged as a safe and effective treatment option for patients with relapsed or refractory leukemia. Unlike T cell-based therapies, NK cells harbor an innate capacity to eliminate malignant cells without prior sensitization and can be adoptively transferred between individuals without the need for extensive HLA matching. A wide variety of therapeutic NK cell sources are currently being investigated clinically, including allogeneic donor-derived NK cells, stem cell-derived NK cells and NK cell lines. However, it is becoming increasingly clear that not all NK cells are endowed with the same antitumor potential. Despite advances in techniques to enhance NK cell cytotoxicity and persistence, the initial identification and utilization of highly functional NK cells remains essential to ensure the future success of adoptive NK cell therapies. Indeed, little consideration has been given to the identification and selection of donors who harbor NK cells with potent antitumor activity. In this regard, there is currently no standard donor selection criteria for adoptive NK cell therapy. Here, we review our current understanding of the factors which govern NK cell functional fate, and propose a paradigm shift away from traditional phenotypic characterization of NK cell subsets towards a functional profile based on molecular and metabolic characteristics. We also discuss previous selection models for NK cell-based immunotherapies and highlight important considerations for the selection of optimal NK cell donors for future adoptive cell therapies. |
format | Online Article Text |
id | pubmed-8578927 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-85789272021-11-11 Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies Barnes, Samantha A. Trew, Isabella de Jong, Emma Foley, Bree Front Immunol Immunology Over the past 20 years natural killer (NK) cell-based immunotherapies have emerged as a safe and effective treatment option for patients with relapsed or refractory leukemia. Unlike T cell-based therapies, NK cells harbor an innate capacity to eliminate malignant cells without prior sensitization and can be adoptively transferred between individuals without the need for extensive HLA matching. A wide variety of therapeutic NK cell sources are currently being investigated clinically, including allogeneic donor-derived NK cells, stem cell-derived NK cells and NK cell lines. However, it is becoming increasingly clear that not all NK cells are endowed with the same antitumor potential. Despite advances in techniques to enhance NK cell cytotoxicity and persistence, the initial identification and utilization of highly functional NK cells remains essential to ensure the future success of adoptive NK cell therapies. Indeed, little consideration has been given to the identification and selection of donors who harbor NK cells with potent antitumor activity. In this regard, there is currently no standard donor selection criteria for adoptive NK cell therapy. Here, we review our current understanding of the factors which govern NK cell functional fate, and propose a paradigm shift away from traditional phenotypic characterization of NK cell subsets towards a functional profile based on molecular and metabolic characteristics. We also discuss previous selection models for NK cell-based immunotherapies and highlight important considerations for the selection of optimal NK cell donors for future adoptive cell therapies. Frontiers Media S.A. 2021-10-27 /pmc/articles/PMC8578927/ /pubmed/34777383 http://dx.doi.org/10.3389/fimmu.2021.765705 Text en Copyright © 2021 Barnes, Trew, de Jong and Foley 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 Barnes, Samantha A. Trew, Isabella de Jong, Emma Foley, Bree Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies |
title | Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies |
title_full | Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies |
title_fullStr | Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies |
title_full_unstemmed | Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies |
title_short | Making a Killer: Selecting the Optimal Natural Killer Cells for Improved Immunotherapies |
title_sort | making a killer: selecting the optimal natural killer cells for improved immunotherapies |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8578927/ https://www.ncbi.nlm.nih.gov/pubmed/34777383 http://dx.doi.org/10.3389/fimmu.2021.765705 |
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