{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:03:35Z","timestamp":1785409415179,"version":"3.56.0"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Allegheny Health Network Cancer Institute Chair Core fund","award":["19467509"],"award-info":[{"award-number":["19467509"]}]},{"award":["19467509"],"award-info":[{"award-number":["19467509"]}],"id":[{"id":"https:\/\/ror.org\/0101kry21","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Ovarian cancer is the most lethal gynecologic malignancy, largely due to late diagnosis and the high prevalence of malignant ascites, a hallmark of advanced disease that is difficult to control and contributes to immune suppression and treatment failure. Despite advances in standard care, durable responses are rare. This study investigates a novel immunotherapeutic strategy designed to overcome the suppressed peritoneal microenvironment using an oncolytic vaccinia virus engineered to express a decoy-resistant IL-18 mutein. Methods: We generated a vaccinia virus (vvDD-nsmDR-18) expressing a non-secreted, mature, decoy-resistant IL-18. Viral expression was validated via RT-qPCR and fluorescence microscopy, while cytotoxicity was confirmed using CCK-8 assays. The antitumor efficacy of vvDD-nsmDR-18 was evaluated in the aggressive murine ID8a ovarian cancer model. The underlying mechanisms of action were investigated using flow cytometry and transcriptional profiling. Results: Treatment with vvDD-nsmDR-18 significantly prolonged survival and was associated with reduced abdominal distension consistent with decreased ascites burden. Immune analyses indicated enhanced T cell activation across multiple anatomical compartments, including tumors, peritoneal cavity, and spleens, the latter recently suggested to serve as a reservoir for tumor-reactive T cells. This systemic activation was characterized by increased IFN-\u03b3 and perforin expression. In addition, vvDD-nsmDR-18 treatment was associated with expansion of CD39+CD103+CD8+ tumor-reactive T cells and a shift toward a lower PD-1 expression phenotype within this population. Conclusions: These findings demonstrate that nsmDR-18-expressing oncolytic viruses can remodel the immunosuppressive landscape of advanced ovarian cancer, suggesting this approach is a promising candidate for further clinical development.<\/jats:p>","DOI":"10.3390\/cancers18071065","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T12:05:49Z","timestamp":1775563549000},"page":"1065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Secreted Mature Decoy-Resistant IL-18-Armed Oncolytic Vaccinia Virus Elicits Potent Antitumor Effects in an Aggressive Murine Ovarian Cancer Model"],"prefix":"10.3390","volume":"18","author":[{"given":"Pingpo","family":"Ming","sequence":"first","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"},{"name":"Taikang Tongji (Wuhan) Hospital, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Li","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"},{"name":"Department of Obstetrics, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Ye","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"},{"name":"Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19104, USA"},{"name":"Department of Cancer Center, Renmin Hospital of Wuhan University, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2463-0640","authenticated-orcid":false,"given":"Lingjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"},{"name":"Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19104, USA"},{"name":"Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Waltermire","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinshun","family":"Zhao","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0216-936X","authenticated-orcid":false,"given":"Maya","family":"Eid","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"},{"name":"College of Arts & Science, Vanderbilt University, Nashville, TN 37235, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2395-2042","authenticated-orcid":false,"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ge","sequence":"additional","affiliation":[{"name":"Taikang Tongji (Wuhan) Hospital, Wuhan 430060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Ren","sequence":"additional","affiliation":[{"name":"Cancer Center, Union Hospital, Huazhong University of Science and Technology, Wuhan 430023, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3099-2613","authenticated-orcid":false,"given":"David L.","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"},{"name":"Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0581-3528","authenticated-orcid":false,"given":"Zuqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Allegheny Health Network Cancer Institute, Pittsburgh, PA 15212, USA"},{"name":"Department of Surgery, Drexel University College of Medicine, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","first-page":"e70043","article-title":"Cancer statistics, 2026","volume":"76","author":"Siegel","year":"2026","journal-title":"CA Cancer J. 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