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Article

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2021-06-01

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cc by (c) Riederer, Stephanie et al., 2021
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/180570

Activation of interferon regulatory factor 3 by replication-competent Vaccinia viruses improves antitumor efficacy mediated by T-cell responses

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https://doi.org/10.1016/j.omto.2021.06.001

Abstract

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 (C10L, N2L, and C6L) from VACV did not reduce the strength of viral replication, both in vitro and in vivo, but resulted in the rescue of IRF3 phosphorylation upon infection of cancer cells. In syngeneic mouse tumor models, this activation translated to enhanced cytotoxic T lymphocyte (CTL) responses directed against tumor-associated antigens and neo-epitopes and improved antitumor activity.

Subject

Vacunes, Tumors, Cèl·lules canceroses, Virus

Subject (English)

Vaccines, Tumors, Cancer cells, Viruses

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Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citation

RIEDERER, Stephanie, et al. Activation of interferon regulatory factor 3 by replication-competent Vaccinia viruses improves antitumor efficacy mediated by T-cell responses. Molecular Therapy - Oncolytics. 2021. Vol. 22, num. 399-409. [consulted: 13 of August of 2026]. Available at: https://hdl.handle.net/2445/180570

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