{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:18:52Z","timestamp":1783948732037,"version":"3.55.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000147","name":"Canadian Cancer Society","doi-asserted-by":"publisher","award":["703497"],"award-info":[{"award-number":["703497"]}],"id":[{"id":"10.13039\/501100000147","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Ovarian cancer (OC) is a leading cause of gynecological cancer-related mortality. Management remains challenging as the disease frequently presents with intra-abdominal metastases at diagnosis, standard therapies can be associated with severe complications and disease recurrence is common. While cellular immunotherapy is increasingly investigated as a promising approach, the most effective routes of administration need to be established. We have investigated NK cell therapeutics as a less toxic option and examined the permanent NK cell line, NK-92, as a suitable model. Here, we report two xenograft mouse models with the ovarian adenocarcinoma cell line, SKOV-3, representing early-stage OC and late-stage OC with ascites to comprehensively evaluate the anti-cancer efficacy of different routes of NK-92 administration. Bioluminescence imaging, cell tracking with the IVIS system and animal survival were used to evaluate outcomes. The cells were administered via intraperitoneal (IP), intravenous (IV), or a combination of IP and IV routes. We showed that NK-92 significantly increased animal survival when delivered IP (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.009 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.018) or combined IP and IV (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.05 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.017) in early and established OC xenografts, respectively, whereas intravenous delivery at similar doses had no effect on survival (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.665 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.052) compared with untreated controls. These findings, and our novel models, have potential implications for enhancing the clinical benefit of NK therapy in patients with advanced OC.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0347095","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:40:04Z","timestamp":1776706804000},"page":"e0347095","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Intraperitoneal administration of NK-92 improves survival in xenografts of early and established ovarian cancer models"],"prefix":"10.1371","volume":"21","author":[{"given":"Paula","family":"Marcus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6709-7018","authenticated-orcid":true,"given":"Jenny","family":"Warrington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manjunatha","family":"Ankathatti-Munegowda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xing-Hua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iran","family":"Rashedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armand","family":"Keating","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"pone.0347095.ref001","doi-asserted-by":"crossref","DOI":"10.21037\/jgo-2020-06","article-title":"Intraperitoneal 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Sterner","year":"2021","journal-title":"Blood Cancer J"},{"issue":"2","key":"pone.0347095.ref005","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/sj.bmt.1704086","article-title":"IL-2-based immunotherapy after autologous transplantation for lymphoma and breast cancer induces immune activation and cytokine release: a phase I\/II trial","volume":"32","author":"LJ Burns","year":"2003","journal-title":"Bone Marrow Transplant"},{"issue":"1","key":"pone.0347095.ref006","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1097\/00002371-200001000-00018","article-title":"Posttransplant adoptive immunotherapy with activated natural killer cells in patients with metastatic breast cancer","volume":"23","author":"M deMagalhaes-Silverman","year":"2000","journal-title":"J Immunother"},{"issue":"11","key":"pone.0347095.ref007","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1158\/1078-0432.CCR-03-0683","article-title":"Treatment of colon and lung cancer patients withex 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Curti","year":"2011","journal-title":"Blood"},{"issue":"1","key":"pone.0347095.ref010","doi-asserted-by":"crossref","first-page":"98","DOI":"10.3109\/14653249.2010.515582","article-title":"A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer","volume":"13","author":"MA Geller","year":"2011","journal-title":"Cytotherapy"},{"issue":"8","key":"pone.0347095.ref011","doi-asserted-by":"crossref","first-page":"3051","DOI":"10.1182\/blood-2004-07-2974","article-title":"Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer","volume":"105","author":"JS Miller","year":"2005","journal-title":"Blood"},{"issue":"5","key":"pone.0347095.ref012","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.jcyt.2022.12.003","article-title":"The NK-92 cell line-30 years later: its impact on natural killer cell research and treatment of cancer","volume":"25","author":"H Klingemann","year":"2023","journal-title":"Cytotherapy"},{"issue":"12","key":"pone.0347095.ref013","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.3390\/cancers17121968","article-title":"The natural killer cell line NK-92 and its genetic variants: impact on NK cell research and cancer immunotherapy","volume":"17","author":"H Klingemann","year":"2025","journal-title":"Cancers"},{"issue":"51","key":"pone.0347095.ref014","doi-asserted-by":"crossref","first-page":"89256","DOI":"10.18632\/oncotarget.19204","article-title":"A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy","volume":"8","author":"BA Williams","year":"2017","journal-title":"Oncotarget"},{"issue":"1","key":"pone.0347095.ref015","article-title":"NK-92 serial killers - characterization of potential limitations to cytotoxic capacity","volume":"206","author":"LT 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chemokine microenvironment","volume":"75","author":"A Ponzetta","year":"2015","journal-title":"Cancer Res"},{"issue":"1","key":"pone.0347095.ref037","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/stem.2230","article-title":"Induced pluripotent stem cell-derived natural killer cells for treatment of ovarian cancer","volume":"34","author":"DL Hermanson","year":"2016","journal-title":"Stem Cells"},{"issue":"6","key":"pone.0347095.ref038","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1007\/s13346-024-01765-w","article-title":"Innovative landscapes in intraperitoneal therapy of ovarian cancer","volume":"15","author":"KP Kumar","year":"2025","journal-title":"Drug Deliv Transl Res"},{"issue":"2","key":"pone.0347095.ref039","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1158\/1078-0432.CCR-22-1893","article-title":"Intraperitoneal Monocytes plus IFNs as a novel cellular immunotherapy for ovarian cancer: mechanistic characterization and results from a Phase I clinical trial","volume":"29","author":"DS Green","year":"2023","journal-title":"Clin Cancer Res"},{"key":"pone.0347095.ref040","unstructured":"Cyclophosphamide Followed by Intravenous and Intraperitoneal Infusion of Autologous T Cells Genetically Engineered to Secrete IL-12 and to Target the MUC16ecto Antigen in Patients With Recurrent MUC16ecto+ Solid Tumors. ClinicalTrials.gov ID NCT02498912."},{"key":"pone.0347095.ref041","article-title":"First-in-human phase I clinical trial evaluating intraperitoneal administration of MOv19-BBz CAR T cells in patients with alpha folate receptor-expressing recurrent high grade serous ovarian cancer","volume":"9","author":"P Shah","year":"2021","journal-title":"J ImmunoTher Cancer"},{"issue":"1","key":"pone.0347095.ref042","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/s41420-024-02077-1","article-title":"Emerging roles of CAR-NK cell therapies in tumor immunotherapy: current status and future directions","volume":"10","author":"Y Zhong","year":"2024","journal-title":"Cell Death Discov"},{"key":"pone.0347095.ref043","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2022.841107","article-title":"iPSC-derived natural killer cell therapies - expansion and targeting","volume":"13","author":"BH Goldenson","year":"2022","journal-title":"Front Immunol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347095","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T17:40:12Z","timestamp":1776706812000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0347095"}},"subtitle":[],"editor":[{"given":"Yusuf Ahmed","family":"Haggag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,4,20]]},"references-count":43,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0347095","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,20]]}}}