Effects of immune checkpoint blockade on antigen-specific CD8
T cells
Tim3
adoptive cellular therapy
checkpoint inhibitor
dendritic cells
Journal
Microbiology and immunology
ISSN: 1348-0421
Titre abrégé: Microbiol Immunol
Pays: Australia
ID NLM: 7703966
Informations de publication
Date de publication:
May 2022
May 2022
Historique:
revised:
12
01
2022
received:
26
07
2021
accepted:
01
02
2022
pubmed:
13
2
2022
medline:
12
5
2022
entrez:
12
2
2022
Statut:
ppublish
Résumé
Adoptive T-cell therapies have been successfully used as prophylaxis or treatment for immunocompromised patients at risk of viral infections or advanced cancers. Unfortunately, for some refractory cancers, they have failed. To overcome this, checkpoint inhibitors are used to rescue immune antitumor responses. We hypothesized that in vitro checkpoint blockade during T-cell stimulation and expansion with messenger RNA (mRNA)-pulsed DCs may enhance the activity of antigen-specific T cells and improve the efficacy of adoptive cellular therapy platforms. Human peripheral blood mononuclear cells were isolated from cytomegalovirus (CMV)-seropositive donors to generate DCs. These were pulsed with CMV matrix phosphoprotein 65 (CMVpp65)-mRNA to educate T cells in coculture for 15 days. Three checkpoint blockade conditions were evaluated (anti-PD1, anti-Tim3, and anti-PD1 + Tim3). IL-2 and antibodies blockades were added every 3 days. Immunophenotyping was performed on Day 0 and Day 15. Polyfunctional antigen-specific responses were evaluated upon rechallenge with CMVpp65 peptides. CMVpp65-activated CD8
Identifiants
pubmed: 35150167
doi: 10.1111/1348-0421.12967
doi:
Substances chimiques
Hepatitis A Virus Cellular Receptor 2
0
Immune Checkpoint Inhibitors
0
Programmed Cell Death 1 Receptor
0
RNA, Messenger
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
201-211Subventions
Organisme : Wells Brain Tumor Center Research Fund
ID : Wells Brain Tumor Center Research Fund
Organisme : Adam Michael Rosen Foundation
ID : Adam Michael Rosen Foundation
Organisme : NIH Clinical Center
ID : R01-CA175517-06
Organisme : NIH Clinical Center
ID : RO1-NS108781-03
Organisme : Clinical and Translational Science Award
ID : Award Standard Language
Informations de copyright
© 2022 The Societies and John Wiley & Sons Australia, Ltd.
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