NK cells specifically TCR-dressed to kill cancer cells.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_C96D4A7DAD14
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
NK cells specifically TCR-dressed to kill cancer cells.
Périodique
EBioMedicine
Auteur(s)
Mensali N., Dillard P., Hebeisen M., Lorenz S., Theodossiou T., Myhre M.R., Fåne A., Gaudernack G., Kvalheim G., Myklebust J.H., Inderberg E.M., Wälchli S.
ISSN
2352-3964 (Electronic)
ISSN-L
2352-3964
Statut éditorial
Publié
Date de publication
02/2019
Peer-reviewed
Oui
Volume
40
Pages
106-117
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Adoptive T-cell transfer of therapeutic TCR holds great promise to specifically kill cancer cells, but relies on modifying the patient's own T cells ex vivo before injection. The manufacturing of T cells in a tailor-made setting is a long and expensive process which could be resolved by the use of universal cells. Currently, only the Natural Killer (NK) cell line NK-92 is FDA approved for universal use. In order to expand their recognition ability, they were equipped with Chimeric Antigen Receptors (CARs). However, unlike CARs, T-cell receptors (TCRs) can recognize all cellular proteins, which expand NK-92 recognition to the whole proteome.
We herein genetically engineered NK-92 to express the CD3 signaling complex, and showed that it rendered them able to express a functional TCR. Functional assays and in vivo efficacy were used to validate these cells.
This is the first demonstration that a non-T cell can exploit TCRs. This TCR-redirected cell line, termed TCR-NK-92, mimicked primary T cells phenotypically, metabolically and functionally, but retained its NK cell effector functions. Our results demonstrate a unique manner to indefinitely produce TCR-redirected lymphocytes at lower cost and with similar therapeutic efficacy as redirected T cells.
These results suggest that an NK cell line could be the basis for an off-the-shelf TCR-based cancer immunotherapy solution. FUND: This work was supported by the Research Council of Norway (#254817), South-Eastern Norway Regional Health Authority (#14/00500-79), by OUS-Radiumhospitalet (Gene Therapy program) and the department of Oncology at the University of Lausanne.
Mots-clé
Animals, Biomarkers, Cell Line, Tumor, Cell Respiration, Cytotoxicity, Immunologic/genetics, Disease Models, Animal, Energy Metabolism, Gene Expression Profiling, Humans, Immunophenotyping, Killer Cells, Natural/immunology, Killer Cells, Natural/metabolism, Mice, Mitochondria/metabolism, Neoplasms/immunology, Neoplasms/metabolism, Neoplasms/pathology, Neoplasms/therapy, Receptors, Antigen, T-Cell/metabolism, Signal Transduction, T-Lymphocyte Subsets/immunology, T-Lymphocyte Subsets/metabolism, Transcriptome, Xenograft Model Antitumor Assays, Immunotherapy, Natural killer, T cell, TCR
Pubmed
Web of science
Open Access
Oui
Création de la notice
18/02/2019 11:06
Dernière modification de la notice
20/08/2019 16:44
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