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Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy

Advancements in chimeric antigen receptor engineered T-cell (CAR-T) therapy have revolutionized treatment for several cancer types over the past decade. Despite this success, obstacles including the high price tag, manufacturing complexity, and treatment-associated toxicities have limited the broad...

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Autores principales: Kilgour, Marisa K., Bastin, Donald J., Lee, Seung-Hwan, Ardolino, Michele, McComb, Scott, Visram, Alissa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187144/
https://www.ncbi.nlm.nih.gov/pubmed/37205115
http://dx.doi.org/10.3389/fimmu.2023.1166038
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author Kilgour, Marisa K.
Bastin, Donald J.
Lee, Seung-Hwan
Ardolino, Michele
McComb, Scott
Visram, Alissa
author_facet Kilgour, Marisa K.
Bastin, Donald J.
Lee, Seung-Hwan
Ardolino, Michele
McComb, Scott
Visram, Alissa
author_sort Kilgour, Marisa K.
collection PubMed
description Advancements in chimeric antigen receptor engineered T-cell (CAR-T) therapy have revolutionized treatment for several cancer types over the past decade. Despite this success, obstacles including the high price tag, manufacturing complexity, and treatment-associated toxicities have limited the broad application of this therapy. Chimeric antigen receptor engineered natural killer cell (CAR-NK) therapy offers a potential opportunity for a simpler and more affordable “off-the-shelf” treatment, likely with fewer toxicities. Unlike CAR-T, CAR-NK therapies are still in early development, with few clinical trials yet reported. Given the challenges experienced through the development of CAR-T therapies, this review explores what lessons we can apply to build better CAR-NK therapies. In particular, we explore the importance of optimizing the immunochemical properties of the CAR construct, understanding factors leading to cell product persistence, enhancing trafficking of transferred cells to the tumor, ensuring the metabolic fitness of the transferred product, and strategies to avoid tumor escape through antigen loss. We also review trogocytosis, an important emerging challenge that likely equally applies to CAR-T and CAR-NK cells. Finally, we discuss how these limitations are already being addressed in CAR-NK therapies, and what future directions may be possible.
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spelling pubmed-101871442023-05-17 Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy Kilgour, Marisa K. Bastin, Donald J. Lee, Seung-Hwan Ardolino, Michele McComb, Scott Visram, Alissa Front Immunol Immunology Advancements in chimeric antigen receptor engineered T-cell (CAR-T) therapy have revolutionized treatment for several cancer types over the past decade. Despite this success, obstacles including the high price tag, manufacturing complexity, and treatment-associated toxicities have limited the broad application of this therapy. Chimeric antigen receptor engineered natural killer cell (CAR-NK) therapy offers a potential opportunity for a simpler and more affordable “off-the-shelf” treatment, likely with fewer toxicities. Unlike CAR-T, CAR-NK therapies are still in early development, with few clinical trials yet reported. Given the challenges experienced through the development of CAR-T therapies, this review explores what lessons we can apply to build better CAR-NK therapies. In particular, we explore the importance of optimizing the immunochemical properties of the CAR construct, understanding factors leading to cell product persistence, enhancing trafficking of transferred cells to the tumor, ensuring the metabolic fitness of the transferred product, and strategies to avoid tumor escape through antigen loss. We also review trogocytosis, an important emerging challenge that likely equally applies to CAR-T and CAR-NK cells. Finally, we discuss how these limitations are already being addressed in CAR-NK therapies, and what future directions may be possible. Frontiers Media S.A. 2023-05-02 /pmc/articles/PMC10187144/ /pubmed/37205115 http://dx.doi.org/10.3389/fimmu.2023.1166038 Text en Copyright © 2023 Kilgour, Bastin, Lee, Ardolino, McComb and Visram 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
Kilgour, Marisa K.
Bastin, Donald J.
Lee, Seung-Hwan
Ardolino, Michele
McComb, Scott
Visram, Alissa
Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy
title Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy
title_full Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy
title_fullStr Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy
title_full_unstemmed Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy
title_short Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy
title_sort advancements in car-nk therapy: lessons to be learned from car-t therapy
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10187144/
https://www.ncbi.nlm.nih.gov/pubmed/37205115
http://dx.doi.org/10.3389/fimmu.2023.1166038
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