Unedited allogeneic iNKT cells show extended persistence in MHC-mismatched canine recipients.
allogeneic invariant natural killer T
biomarkers
canine model
donor selection
donor-recipient MHC mismatch
off-the-shelf adoptive cell therapy
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
17 10 2023
17 10 2023
Historique:
received:
07
12
2022
revised:
14
08
2023
accepted:
20
09
2023
medline:
23
10
2023
pubmed:
19
10
2023
entrez:
18
10
2023
Statut:
ppublish
Résumé
Allogeneic invariant natural killer T cells (allo-iNKTs) induce clinical remission in patients with otherwise incurable cancers and COVID-19-related acute respiratory failure. However, their functionality is inconsistent among individuals, and they become rapidly undetectable after infusion, raising concerns over rejection and limited therapeutic potential. We validate a strategy to promote allo-iNKT persistence in dogs, an established large-animal model for novel cellular therapies. We identify donor-specific iNKT biomarkers of survival and sustained functionality, conserved in dogs and humans and retained upon chimeric antigen receptor engineering. We reason that infusing optimal allo-iNKTs enriched in these biomarkers will prolong their persistence without requiring MHC ablation, high-intensity chemotherapy, or cytokine supplementation. Optimal allo-iNKTs transferred into MHC-mismatched dogs remain detectable for at least 78 days, exhibiting sustained immunomodulatory effects. Our canine model will accelerate biomarker discovery of optimal allo-iNKT products, furthering application of MHC-unedited allo-iNKTs as a readily accessible universal platform to treat incurable conditions worldwide.
Identifiants
pubmed: 37852175
pii: S2666-3791(23)00418-4
doi: 10.1016/j.xcrm.2023.101241
pmc: PMC10591065
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
101241Subventions
Organisme : NCI NIH HHS
ID : K08 CA252619
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA224122
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA272270
Pays : United States
Organisme : NIH HHS
ID : P40 OD010939
Pays : United States
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Authors declare that they have no competing interests.
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