Chimeric Antigen Receptors Targeting Human Cytomegalovirus.
cellular immunity
chimeric antigen receptor
human cytomegalovirus
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
04 08 2020
04 08 2020
Historique:
received:
11
02
2020
accepted:
10
04
2020
pubmed:
15
4
2020
medline:
3
3
2021
entrez:
15
4
2020
Statut:
ppublish
Résumé
Human cytomegalovirus (CMV) is a ubiquitous pathogen that causes significant morbidity in some vulnerable populations. Individualized adoptive transfer of ex vivo expanded CMV-specific CD8+ T cells has provided proof-of-concept that immunotherapy can be highly effective, but a chimeric antigen receptor (CAR) approach would provide a feasible method for broad application. We created 8 novel CARs using anti-CMV neutralizing antibody sequences, which were transduced via lentiviral vector into primary CD8+ T cells. All CARs were expressed. Activity against CMV-infected target cells was assessed by release of cytokines (interferon-γ and tumor necrosis factor-α), upregulation of surface CD107a, proliferation, cytolysis of infected cells, and suppression of viral replication. While some CARs showed varying functional activity across these assays, 1 CAR based on antibody 21E9 was consistently superior in all measures. These results support development of a CMV-specific CAR for therapeutic use against CMV and potentially other applications harnessing CMV-driven immunotherapies.
Identifiants
pubmed: 32285133
pii: 5819787
doi: 10.1093/infdis/jiaa171
pmc: PMC7399702
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Receptors, Chimeric Antigen
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
853-862Subventions
Organisme : NIAID NIH HHS
ID : R01 AI103960
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI128913
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA181045
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA033572
Pays : United States
Organisme : NIAID NIH HHS
ID : P30 AI028697
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA111412
Pays : United States
Informations de copyright
© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
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