biostudies-literatureSibal PAJapan Grant-in-Aid for Scientific ResearchTakara Bio, Inc1259-1277https://www.ebi.ac.uk/biostudies/studies/S-EPMC11076993biostudies-literatureUnknown18(5)Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)-interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING-IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored. Here, we explored the antitumor efficacy of combining an HSV-1-based OV, C-REV, with a membrane-impermeable STING agonist, 2'3'-GAMP. Our results demonstrated that tumor cells harbor a largely defective STING-IFN pathway, therebMolecular oncologySTING activator 2'3'-cGAMP enhanced HSV-1-based oncolytic viral therapy.PMC1107699318H0269116H0541316K15611Morimoto DEissa IRKasuya HIchinose TMukoyama NNaoe YSibal PAAbdelmoneim MAboalela MAMMatsumura SBustos-Villalobos ITanaka MfalseSTING activator 2'3'-cGAMP enhanced HSV-1-based oncolytic viral therapy.Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)-interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING-IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored. Here, we explored the antitumor efficacy of combining an HSV-1-based OV, C-REV, with a membrane-impermeable STING agonist, 2'3'-GAMP. Our results demonstrated that tumor cells harbor a largely defective STING-IFN pathway, thereb2024-01-01T00:00:00Z2024 May2026-06-01T23:43:05.718Z2026-05-23T03:08:06.137ZS-EPMC110769933840059710.1002/1878-0261.13603