Advancements in CAR-NK therapy: lessons to be learned from CAR-T therapy.
T cell
cancer
chimeric antigen receptor
immunotherapy
natural kill cell
trogocytosis
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
14
02
2023
accepted:
12
04
2023
medline:
22
5
2023
pubmed:
19
5
2023
entrez:
19
5
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37205115
doi: 10.3389/fimmu.2023.1166038
pmc: PMC10187144
doi:
Substances chimiques
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1166038Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
Copyright © 2023 Kilgour, Bastin, Lee, Ardolino, McComb and Visram.
Déclaration de conflit d'intérêts
MA received monetary compensation from Alloy Therapeutics for consulting. MA is under a contract agreement to perform sponsored research with Actym Therapeutics and Dragonfly Therapeutics. Neither consulting nor sponsored research is related to the present article. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.
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