{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nakatake M"],"funding":["Japan Agency for Medical Research and Development","Japan Society for the Promotion of Science"],"pagination":["600-610"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10859623"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["115(2)"],"pubmed_abstract":["Oncolytic viruses have two anticancer functions: direct oncolysis and elicitation of antitumor immunity. We previously developed a novel fusogenic oncolytic vaccinia virus (FUVAC) from a non-fusogenic vaccinia virus (VV) and, by remodeling the tumor immune microenvironment, we demonstrated that FUVAC induced stronger oncolysis and antitumor immune responses compared with non-fusogenic VV. These functions depend strongly on cell-cell fusion induction. However, FUVAC tends to have decreased fusion activity in cells with low virus replication efficacy. Therefore, another combination strategy was required to increase cell-cell fusion in these cells. Histone deacetylase (HDAC) inhibitors suppress the host virus defense response and promote viral replication. Therefore, in this study, we selected an HDAC inhibitor, trichostatin A (TSA), as the combination agent for FUVAC to enhance its fusion-based antitumor potential. TSA was added prior to FUVAC treatment of murine tumor B16-F10 and CT26 cells. TSA increased the replication of both FUVAC and parental non-fusogenic VV. Moreover, TSA enhanced cell-cell fusion and FUVAC cytotoxicity in these tumor cells in a dose-dependent manner. Transcriptome analysis revealed that TSA-treated tumors showed altered expression of cellular component-related genes, which may affect fusion tolerance. In a bilateral tumor-bearing mouse model, combination treatment of TSA and FUVAC significantly prolonged mouse survival compared with either treatment alone or in combination with non-fusogenic VV. Our findings demonstrate that TSA is a potent enhancer of cell-cell fusion efficacy of FUVAC."],"journal":["Cancer science"],"pubmed_title":["Histone deacetylase inhibitor boosts anticancer potential of fusogenic oncolytic vaccinia virus by enhancing cell-cell fusion."],"pmcid":["PMC10859623"],"funding_grant_id":["JP22am0401017","21K20837","23K14618"],"pubmed_authors":["Kurosaki H","Nakamura T","Nakatake M"],"additional_accession":[]},"is_claimable":false,"name":"Histone deacetylase inhibitor boosts anticancer potential of fusogenic oncolytic vaccinia virus by enhancing cell-cell fusion.","description":"Oncolytic viruses have two anticancer functions: direct oncolysis and elicitation of antitumor immunity. We previously developed a novel fusogenic oncolytic vaccinia virus (FUVAC) from a non-fusogenic vaccinia virus (VV) and, by remodeling the tumor immune microenvironment, we demonstrated that FUVAC induced stronger oncolysis and antitumor immune responses compared with non-fusogenic VV. These functions depend strongly on cell-cell fusion induction. However, FUVAC tends to have decreased fusion activity in cells with low virus replication efficacy. Therefore, another combination strategy was required to increase cell-cell fusion in these cells. Histone deacetylase (HDAC) inhibitors suppress the host virus defense response and promote viral replication. Therefore, in this study, we selected an HDAC inhibitor, trichostatin A (TSA), as the combination agent for FUVAC to enhance its fusion-based antitumor potential. TSA was added prior to FUVAC treatment of murine tumor B16-F10 and CT26 cells. TSA increased the replication of both FUVAC and parental non-fusogenic VV. Moreover, TSA enhanced cell-cell fusion and FUVAC cytotoxicity in these tumor cells in a dose-dependent manner. Transcriptome analysis revealed that TSA-treated tumors showed altered expression of cellular component-related genes, which may affect fusion tolerance. In a bilateral tumor-bearing mouse model, combination treatment of TSA and FUVAC significantly prolonged mouse survival compared with either treatment alone or in combination with non-fusogenic VV. Our findings demonstrate that TSA is a potent enhancer of cell-cell fusion efficacy of FUVAC.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Feb","modification":"2026-06-04T09:51:16.07Z","creation":"2025-04-04T08:07:40.019Z"},"accession":"S-EPMC10859623","cross_references":{"pubmed":["38037288"],"doi":["10.1111/cas.16032"]}}