Developing Allogeneic Double-Negative T Cells as a Novel Off-the-Shelf Adoptive Cellular Therapy for Cancer.
Animals
Biomarkers
Cytotoxicity, Immunologic
Disease Models, Animal
Female
Flow Cytometry
Humans
Immunohistochemistry
Immunophenotyping
Immunotherapy, Adoptive
/ methods
Mice
Mice, Knockout
Neoplasms
/ immunology
T-Lymphocyte Subsets
/ immunology
Transplantation, Homologous
Treatment Outcome
Xenograft Model Antitumor Assays
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
01 04 2019
01 04 2019
Historique:
received:
20
07
2018
revised:
19
11
2018
accepted:
03
01
2019
pubmed:
9
1
2019
medline:
12
5
2020
entrez:
9
1
2019
Statut:
ppublish
Résumé
To expand clinical-grade healthy donor-derived double-negative T cells (DNT) to a therapeutically relevant number and characterize their potential to be used as an "off-the-shelf" adoptive cellular therapy (ACT) against cancers. We developed methods to expand DNTs under GMP conditions and characterized their surface molecule expression pattern using flow cytometry-based high-throughput screening. We investigated the off-the-shelf potential of clinical-grade DNTs by assessing their cytotoxicity against various cancer types and their off-tumor toxicity Clinical-grade DNTs expanded 1,558 ± 795.5-fold in 17 days with >90% purity. Expanded DNTs showed potent We have established a method to generate therapeutic numbers of clinical-grade DNTs that fulfill the requirements of an off-the-shelf ACT.
Identifiants
pubmed: 30617140
pii: 1078-0432.CCR-18-2291
doi: 10.1158/1078-0432.CCR-18-2291
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2241-2253Subventions
Organisme : CIHR
ID : 141723
Pays : Canada
Informations de copyright
©2019 American Association for Cancer Research.