Activation of interferon regulatory factor 3 by replication-competent vaccinia viruses improves antitumor efficacy mediated by T cell responses.
cancer virotherapy
immunmodulation
immunotherapy
poxvirus
vaccina virus replication
Journal
Molecular therapy oncolytics
ISSN: 2372-7705
Titre abrégé: Mol Ther Oncolytics
Pays: United States
ID NLM: 101666776
Informations de publication
Date de publication:
24 Sep 2021
24 Sep 2021
Historique:
received:
17
12
2020
accepted:
01
06
2021
entrez:
23
9
2021
pubmed:
24
9
2021
medline:
24
9
2021
Statut:
epublish
Résumé
Recently, oncolytic vaccinia viruses (VACVs) have shown their potential to provide for clinically effective cancer treatments. The reason for this clinical usefulness is not only the direct destruction of infected cancer cells but also activation of immune responses directed against tumor antigens. For eliciting a robust antitumor immunity, a dominant T helper 1 (Th1) cell differentiation of the response is preferred, and such polarization can be achieved by activating the Toll-like receptor 3 (TLR3)-interferon regulatory factor 3 (IRF3) signaling pathway. However, current VACVs used as oncolytic viruses to date still encode several immune evasion proteins involved in the inhibition of this signaling pathway. By inactivating genes of selected regulatory virus proteins, we aimed for a candidate virus with increased potency to activate cellular antitumor immunity but at the same time with a fully maintained replicative capacity in cancer cells. The removal of up to three key genes (
Identifiants
pubmed: 34553028
doi: 10.1016/j.omto.2021.06.001
pii: S2372-7705(21)00080-2
pmc: PMC8430050
doi:
Types de publication
Journal Article
Langues
eng
Pagination
399-409Informations de copyright
© 2021 The Author(s).
Déclaration de conflit d'intérêts
The authors declare no competing interests.
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