{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:21:17Z","timestamp":1788265277040,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017646","name":"Ovacure Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Patients with ovarian cancer (OC) have not yet benefitted from the advances in immuno\u2010oncology. While tumor infiltrating lymphocytes (TILs) can be expanded from OC tumors, previous trials have not demonstrated lasting responses. High expression of the immune checkpoints PD\u20101 and LAG\u20103 on TILs from OC provide a rationale for the addition of immune checkpoint inhibitors (ICI) to the treatment. In this clinical pilot study (NCT04611126), five patients with platinum\u2010resistant recurrent OC were treated with TIL therapy and up to four cycles of combined treatment with PD\u20101\u2010\/LAG\u20103\u2010inhibitors. The primary endpoint was safety and feasibility, while secondary endpoints included immune monitoring and clinical efficacy. Included patients had undifferentiated carcinoma (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20091), high\u2010grade serous OC (HGSOC) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092) and low\u2010grade serous OC (LGSOC) (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092). The treatment was safe and feasible with expected treatment\u2010related toxicity; however, there was a relatively high rate of non\u2010treatment\u2010related complications. A decrease in tumor burden was observed in 80% (4\/5) of patients, including two unconfirmed partial responses. In one patient, the response was supported by in\u00a0vitro reactivity of the infused TILs toward autologous tumor cell line. Differences in baseline tumor burden, infusion product composition and responses were observed in LGSOC vs. HGSOC. Overall, this exploratory pilot study demonstrated a favorable safety profile and indications of clinical efficacy for TIL therapy combined with PD\u20101 and LAG\u20103 inhibition in platinum\u2010resistant OC. Due to the low patient number, the results should be interpreted as hypothesis\u2010generating, providing a rationale for conducting larger trials that carefully consider treatment timing and tumor histology.\n                  <\/jats:p>","DOI":"10.1002\/ijc.70510","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T04:21:44Z","timestamp":1777004504000},"page":"1735-1749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor Infiltrating Lymphocyte Therapy Combined With\n                    <scp>PD<\/scp>\n                    \u20101\/\n                    <scp>LAG<\/scp>\n                    \u20103 Inhibition in Patients With Recurrent Platinum\u2010Resistant Ovarian Cancer"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7217-2974","authenticated-orcid":false,"given":"Tine J.","family":"Monberg","sequence":"first","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathrine L.","family":"Lorentzen","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie C. W.","family":"Westergaard","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine Z.","family":"Iversen","sequence":"additional","affiliation":[{"name":"Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Troels H.","family":"Borch","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4966-9752","authenticated-orcid":false,"given":"Marco","family":"Donia","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid M.","family":"Mannering","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stine E. W.","family":"Banke","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6zcan","family":"Met","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"},{"name":"Department of Health Technology The Technical University of Denmark (DTU)  Kgs. Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge Marie","family":"Svane","sequence":"additional","affiliation":[{"name":"National Center for Cancer Immune Therapy (CCIT\u2010DK), Department of Oncology Copenhagen University Hospital  Herlev Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41571\u2010024\u201000881\u20103"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1159\/000479006"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyad079"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13551"},{"key":"e_1_2_12_7_1","unstructured":"U.S. Food and Drug Administration \u201cFDA Approves Bevacizumab in Combination With Chemotherapy for Ovarian Cancer \u201d2018 https:\/\/www.fda.gov\/drugs\/resources\u2010information\u2010approved\u2010drugs\/fda\u2010approves\u2010bevacizumab\u2010combination\u2010chemotherapy\u2010ovarian\u2010cancer."},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2024.104434"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.21037\/gs\u201020\u2010413"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/1758835923"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/medicina59071183"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34350"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384047.2015.1040960"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdz135"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.6258"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.19.02059"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416\u2010019\u20100384\u2010y"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ogx.0000889880.15740.ee"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2024.04.001"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2018.1502905"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27604"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20103083.2011.02640.x"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2014.02.004"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.705422"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2019.103208"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2008.08.010"},{"key":"e_1_2_12_27_1","doi-asserted-by":"crossref","unstructured":"H.Wickham \u201cggplot2: Elegant Graphics for Data Analysis \u201d2016.","DOI":"10.1007\/978-3-319-24277-4_9"},{"key":"e_1_2_12_28_1","volume-title":"GGsurvfit\u2014Modeling Survival Data: Extending the Cox Model","author":"Terry M.","year":"2000"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.21105\/joss.01686"},{"key":"e_1_2_12_30_1","unstructured":"U.S. Department of Health and Human Services \u201cCommon Terminology Criteria for Adverse Events (CTCAE) Version 5.0 \u201d2017 National Institutes of Health National Cancer Institute https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/ctc.htm#ctc_50."},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.01.007"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers15235694"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2024012922"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2109970"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002764.pub2"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soi.2024.100046"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.16_suppl.e24036"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1415117"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33395"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102023\u2010008640"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcyt.2021.03.003"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201015\u20101879"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201011\u20100116"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201016\u20101692"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102021\u2010003499"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1080\/08830180902978120"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.3290.Dose\u2010Response"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164\u2010025\u201000627\u20106"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2024.42.17_suppl.LBA5500"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1388663"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2022.05.519"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14215332"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102023\u2010007697"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70510","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70510","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70510","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:56:40Z","timestamp":1788263800000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70510"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":52,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1002\/ijc.70510"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70510","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"assertion":[{"value":"2025-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}