{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T23:54:35Z","timestamp":1790985275018,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T00:00:00Z","timestamp":1694822400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000005","name":"Department of Defense Idea Award","doi-asserted-by":"publisher","award":["CA180425"],"award-info":[{"award-number":["CA180425"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We studied the immunotherapeutic potential of CF33-hNIS-antiPDL1 oncolytic virus (OV) against gastric cancer with peritoneal metastasis (GCPM). We collected fresh malignant ascites (MA) or peritoneal washings (PW) during routine paracenteses and diagnostic laparoscopies from GC patients (n = 27). Cells were analyzed for cancer cell markers and T cells, or treated with PBS, CF33-GFP, or CF33-hNIS-antiPDL1 (MOI = 3). We analyzed infectivity, replication, cytotoxicity, CD107\u03b1 upregulation of CD8+ and CD4+ T cells, CD274 (PD-L1) blockade of cancer cells by virus-encoded anti-PD-L1 scFv, and the release of growth factors and cytokines. We observed higher CD45\u2212\/large-size cells and lower CD8+ T cell percentages in MA than PW. CD45\u2212\/large-size cells were morphologically malignant and expressed CD274 (PD-L1), CD252 (OX40L), and EGFR. CD4+ and CD8+ T cells did not express cell surface exhaustion markers. Virus infection and replication increased cancer cell death at 15 h and 48 h. CF33-hNIS-antiPDL1 treatment produced functional anti-PD-L1 scFv, which blocked surface PD-L1 binding of live cancer cells and increased CD8+CD107\u03b1+ and CD4+CD107\u03b1+ T cell percentages while decreasing EGF, PDGF, soluble anti-PD-L1, and IL-10. CF33-OVs infect, replicate in, express functional proteins, and kill ex vivo GCPM cells with immune-activating effects. CF33-hNIS-antiPDL1 displays real potential for intraperitoneal GCPM therapy.<\/jats:p>","DOI":"10.3390\/ijms241814189","type":"journal-article","created":{"date-parts":[[2023,9,17]],"date-time":"2023-09-17T06:36:45Z","timestamp":1694932605000},"page":"14189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Anti-Tumor Immunogenicity of the Oncolytic Virus CF33-hNIS-antiPDL1 against Ex Vivo Peritoneal Cells from Gastric Cancer Patients"],"prefix":"10.3390","volume":"24","author":[{"given":"Zhifang","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9543-5458","authenticated-orcid":false,"given":"Shyambabu","family":"Chaurasiya","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7692-8874","authenticated-orcid":false,"given":"Anthony K.","family":"Park","sequence":"additional","affiliation":[{"name":"Cancer Immunotherapeutics Program, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-In","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Valencia","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuman","family":"Fong","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanghee","family":"Woo","sequence":"additional","affiliation":[{"name":"Department of Surgery, City of Hope National Medical Center, Duarte, CA 91010, USA"},{"name":"Cancer Immunotherapeutics Program, Beckman Research Institute of City of Hope National Medical Center, Duarte, CA 91010, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1097\/01.sla.0000143245.28656.15","article-title":"Patterns of initial recurrence in completely resected gastric adenocarcinoma","volume":"240","author":"Gonen","year":"2004","journal-title":"Ann. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Rijken, A., Lurvink, R.J., Luyer, M.D.P., Nieuwenhuijzen, G.A.P., van Erning, F.N., van Sandick, J.W., and de Hingh, I. (2021). The Burden of Peritoneal Metastases from Gastric Cancer: A Systematic Review on the Incidence, Risk Factors and Survival. J. Clin. Med., 10.","DOI":"10.3390\/jcm10214882"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"569","DOI":"10.4251\/wjgo.v12.i5.569","article-title":"Gastric cancer with peritoneal metastases: Efficiency of standard treatment methods","volume":"12","author":"Yarema","year":"2020","journal-title":"World J. Gastrointest. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3954","DOI":"10.1245\/s10434-014-3781-8","article-title":"Laparoscopic narrow-band imaging for the diagnosis of peritoneal metastasis in gastric cancer","volume":"21","author":"Kikuchi","year":"2014","journal-title":"Ann. Surg. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"52307","DOI":"10.18632\/oncotarget.10740","article-title":"Metastatic spread in patients with gastric cancer","volume":"7","author":"Riihimaki","year":"2016","journal-title":"Oncotarget"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10936","DOI":"10.3748\/wjg.v21.i39.10936","article-title":"Evaluation and treatment of malignant ascites secondary to gastric cancer","volume":"21","author":"Maeda","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1002\/ijc.28373","article-title":"Peritoneal carcinomatosis of gastric origin: A population-based study on incidence, survival and risk factors","volume":"134","author":"Thomassen","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Sun, B.J., and Lee, B. (2022). Review of Regional Therapies for Gastric Cancer with Peritoneal Metastases. Cancers, 14.","DOI":"10.3390\/cancers14030570"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1080\/14728222.2021.1971195","article-title":"Emerging therapeutic targets for gastric cancer from a host-Helicobacter pylori interaction perspective","volume":"25","author":"Abdi","year":"2021","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Chaurasiya, S., Fong, Y., and Warner, S.G. (2021). Oncolytic Virotherapy for Cancer: Clinical Experience. Biomedicines, 9.","DOI":"10.3390\/biomedicines9040419"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"229","DOI":"10.5501\/wjv.v10.i5.229","article-title":"Oncolytic virus therapy in cancer: A current review","volume":"10","year":"2021","journal-title":"World J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41571-022-00719-w","article-title":"Therapy with oncolytic viruses: Progress and challenges","volume":"20","author":"Shalhout","year":"2023","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1001\/jamaoncol.2016.2064","article-title":"Oncolytic Viruses in Cancer Treatment: A Review","volume":"3","author":"Lawler","year":"2017","journal-title":"JAMA Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"790150","DOI":"10.3389\/fcell.2021.790150","article-title":"Oncolytic Virotherapy: From Bench to Bedside","volume":"9","author":"Yang","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1007\/s10549-014-3180-7","article-title":"A novel vaccinia virus with dual oncolytic and anti-angiogenic therapeutic effects against triple-negative breast cancer","volume":"148","author":"Gholami","year":"2014","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/s41573-018-0007-y","article-title":"Approaches to treat immune hot, altered and cold tumours with combination immunotherapies","volume":"18","author":"Galon","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.jaci.2013.06.006","article-title":"Viral infection of the lung: Host response and sequelae","volume":"132","author":"Yoo","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-biochem-061516-044813","article-title":"Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA","volume":"86","author":"Kato","year":"2017","journal-title":"Annu. Rev. Biochem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1038\/s41573-019-0029-0","article-title":"Optimizing oncolytic virotherapy in cancer treatment","volume":"18","author":"Harrington","year":"2019","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1038\/s41417-021-00350-4","article-title":"CF33-hNIS-antiPDL1 virus primes pancreatic ductal adenocarcinoma for enhanced anti-PD-L1 therapy","volume":"29","author":"Zhang","year":"2022","journal-title":"Cancer Gene Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1729300","DOI":"10.1080\/2162402X.2020.1729300","article-title":"Oncolytic poxvirus CF33-hNIS-DeltaF14.5 favorably modulates tumor immune microenvironment and works synergistically with anti-PD-L1 antibody in a triple-negative breast cancer model","volume":"9","author":"Chaurasiya","year":"2020","journal-title":"Oncoimmunology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e006280","DOI":"10.1136\/jitc-2022-006280","article-title":"Development of the oncolytic virus, CF33, and its derivatives for peritoneal-directed treatment of gastric cancer peritoneal metastases","volume":"11","author":"Yang","year":"2023","journal-title":"J. Immunother. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.jamcollsurg.2019.12.027","article-title":"Novel Chimeric Immuno-Oncolytic Virus CF33-hNIS-antiPDL1 for the Treatment of Pancreatic Cancer","volume":"230","author":"Woo","year":"2020","journal-title":"J. Am. Coll. Surg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1080\/14737140.2016.1224666","article-title":"The current status of immunotherapy in peritoneal carcinomatosis","volume":"16","author":"Strohlein","year":"2016","journal-title":"Expert. Rev. Anticancer. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.suronc.2019.01.005","article-title":"HIPEC and CRS in peritoneal metastatic gastric cancer\u2014Who really benefits?","volume":"28","author":"Hotopp","year":"2019","journal-title":"Surg. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.21873\/anticanres.14174","article-title":"Outcome in Patients Treated With Cytoreductive Surgery and HIPEC for Gastric Cancer With Peritoneal Carcinomatosis","volume":"40","author":"Braeuer","year":"2020","journal-title":"Anticancer. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s40364-020-00228-x","article-title":"Roles of IFN-gamma in tumor progression and regression: A review","volume":"8","author":"Jorgovanovic","year":"2020","journal-title":"Biomark. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"101280","DOI":"10.1016\/j.smim.2019.05.002","article-title":"IFN-gamma: A cytokine at the right time, is in the right place","volume":"43","author":"Burke","year":"2019","journal-title":"Semin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1158\/1078-0432.CCR-16-3232","article-title":"Phase I Trial of Intravenous Oncolytic Vaccinia Virus (GL-ONC1) with Cisplatin and Radiotherapy in Patients with Locoregionally Advanced Head and Neck Carcinoma","volume":"23","author":"Mell","year":"2017","journal-title":"Clin. Cancer Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4388","DOI":"10.1158\/1078-0432.CCR-18-0244","article-title":"Phase I Study of Oncolytic Vaccinia Virus GL-ONC1 in Patients with Peritoneal Carcinomatosis","volume":"24","author":"Lauer","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1038\/mt.2015.109","article-title":"Phase 1b Trial of Biweekly Intravenous Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus in Colorectal Cancer","volume":"23","author":"Park","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/978-1-4939-2727-2_19","article-title":"A Phase 2, Open-Label, Randomized Study of Pexa-Vec (JX-594) Administered by Intratumoral Injection in Patients with Unresectable Primary Hepatocellular Carcinoma","volume":"1317","author":"Breitbach","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nm.3089","article-title":"Randomized dose-finding clinical trial of oncolytic immunotherapeutic vaccinia JX-594 in liver cancer","volume":"19","author":"Heo","year":"2013","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1038\/mt.2016.101","article-title":"Phase 1 Study of Intravenous Oncolytic Poxvirus (vvDD) in Patients with Advanced Solid Cancers","volume":"24","author":"Guo","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1038\/mt.2014.194","article-title":"First-in-man study of western reserve strain oncolytic vaccinia virus: Safety, systemic spread, and antitumor activity","volume":"23","author":"Zeh","year":"2015","journal-title":"Mol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1093\/annonc\/mdw440","article-title":"Vectorized gene therapy of liver tumors: Proof-of-concept of TG4023 (MVA-FCU1) in combination with flucytosine","volume":"28","author":"Husseini","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"712754","DOI":"10.3389\/fonc.2021.712754","article-title":"Targeted Sequencing of Ascites and Peritoneal Washing Fluid of Patients With Gastrointestinal Cancers and Their Clinical Applications and Limitations","volume":"11","author":"Bae","year":"2021","journal-title":"Front. Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:52:19Z","timestamp":1760129539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/18\/14189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,16]]},"references-count":37,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["ijms241814189"],"URL":"https:\/\/doi.org\/10.3390\/ijms241814189","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,16]]}}}