Generation of NK cells with chimeric-switch receptors to overcome PD1-mediated inhibition in cancer immunotherapy.
Antibody-dependent cellular cytotoxicity
Chimeric switch receptor
Hematologic neoplasms
Immunotherapy
Natural killer cells
Programmed cell death 1 receptor
Journal
Cancer immunology, immunotherapy : CII
ISSN: 1432-0851
Titre abrégé: Cancer Immunol Immunother
Pays: Germany
ID NLM: 8605732
Informations de publication
Date de publication:
May 2023
May 2023
Historique:
received:
11
04
2022
accepted:
25
10
2022
medline:
19
4
2023
pubmed:
11
11
2022
entrez:
10
11
2022
Statut:
ppublish
Résumé
Multiple myeloma (MM) is an incurable hematological cancer, in which immune checkpoint inhibition (ICI) with monoclonal antibodies (mAbs) has failed due to uncontrollable immune responses in combination therapies and lack of efficacy in monotherapies. Although NK cell-specific checkpoint targets such as NKG2A and KIRs are currently being evaluated in clinical trials, the clinical impact of NK cells on the PD1 cascade is less well understood compared to T cells. Furthermore, while NK cells have effector activity within the TME, under continuous ligand exposure, NK cell dysfunctionality may occur due to interaction of PD1 and its ligand PD-L1. Due to above-mentioned factors, we designed novel NK cell specific PD1-based chimeric switch receptors (PD1-CSR) by employing signaling domains of DAP10, DAP12 and CD3ζ to revert NK cell inhibition and retarget ICI. PD1-CSR modified NK cells showed increased degranulation, cytokine secretion and cytotoxicity upon recognition of PD-L1
Identifiants
pubmed: 36355079
doi: 10.1007/s00262-022-03317-y
pii: 10.1007/s00262-022-03317-y
pmc: PMC10110653
doi:
Substances chimiques
B7-H1 Antigen
0
Ligands
0
Cytokines
0
Receptors, Natural Killer Cell
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1153-1167Subventions
Organisme : VINNOVA
ID : 2019-00056
Organisme : Radiumhemmets Forskningsfonder
ID : 191063
Informations de copyright
© 2022. The Author(s).
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