{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:16:45Z","timestamp":1788617805462,"version":"build-2803163510"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19K19194"],"award-info":[{"award-number":["JP19K19194"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20K18721"],"award-info":[{"award-number":["JP20K18721"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K10137"],"award-info":[{"award-number":["JP21K10137"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP18ck0106416"],"award-info":[{"award-number":["JP18ck0106416"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP20lm0203140"],"award-info":[{"award-number":["JP20lm0203140"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24am0521005"],"award-info":[{"award-number":["JP24am0521005"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP24bm1223021"],"award-info":[{"award-number":["JP24bm1223021"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cervical lymph node metastasis is a major predictor of poor prognosis in patients with oral squamous cell carcinoma (OSCC), underscoring the need for therapies that effectively target metastatic spread. We previously reported that G47\u0394, a third\u2010generation oncolytic herpes simplex virus type 1 (HSV\u20101), rapidly traffics from tongue tumors to cervical lymph nodes and suppresses metastasis in murine models. Based on this lymphotropic property and the immunological significance of CD28\u2013B7\u20101 interactions for T\u2010cell activation, we pursue the potential of T\u2010mB7\u20101, a new G47\u0394\u2010derived oncolytic HSV\u20101 expressing soluble murine B7\u20101. T\u2010mB7\u20101 secreted soluble B7\u20101 in\u00a0vitro without compromising cytopathic activity. In\u00a0vivo, intratumoral T\u2010mB7\u20101 suppressed tumor growth in the resistant KLN205\u2010MUC1 subcutaneous model and prolonged survival in SCCVII orthotopic tongue tumors. In the KLN205\u2010MUC1 orthotopic tongue cancer that exhibits rapid lymphatic metastasis, a single dose of T\u2010mB7\u20101, but not the control virus T\u201001, significantly reduced cervical lymph node metastasis and improved survival. Repeated low\u2010dose T\u2010mB7\u20101 further caused near\u2010complete suppression of lymph node metastasis and markedly extended survival. Flow cytometry showed both T\u201001 and T\u2010mB7\u20101 induced CD69\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell activation in cervical lymph nodes at 18\u2009h, which was reduced with T\u2010mB7\u20101 at 24\u2009h. Importantly, combining T\u2010mB7\u20101 with systemic CTLA\u20104 blockade markedly prolonged survival of mice harboring orthotopic KLN205\u2010MUC1 tumors, with all treated mice surviving beyond 80\u2009days in the otherwise fatal model. These findings demonstrate that soluble B7\u20101\u2010expressing oncolytic HSV\u20101 combined with CTLA\u20104 blockade durably suppresses lymph node metastasis, providing a promising and minimally invasive strategy for regionally metastatic OSCC.\n                  <\/jats:p>","DOI":"10.1111\/cas.70410","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:37:06Z","timestamp":1778027826000},"page":"1961-1974","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Triple\u2010Mutated\n                    <scp>HSV<\/scp>\n                    \u20101 Expressing Soluble\n                    <scp>B7<\/scp>\n                    \u20101 Plus\n                    <scp>CTLA<\/scp>\n                    \u20104 Blockade Suppresses Lymph Node Metastasis in Tongue Cancer"],"prefix":"10.1111","volume":"117","author":[{"given":"Akinari","family":"Sugauchi","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Uchihashi","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotaka","family":"Ito","sequence":"additional","affiliation":[{"name":"Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miwako","family":"Iwai","sequence":"additional","affiliation":[{"name":"Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzuri","family":"Tsurumaki Sato","sequence":"additional","affiliation":[{"name":"Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Kurioka","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sena Zeynep","family":"Usta","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minoru","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikihiko","family":"Kogo","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susumu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry The University of Osaka  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Fukuhara","sequence":"additional","affiliation":[{"name":"Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"},{"name":"Department of Urology Kyorin University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0523-8010","authenticated-orcid":false,"given":"Tomoki","family":"Todo","sequence":"additional","affiliation":[{"name":"Division of Innovative Cancer Therapy, Advanced Clinical Research Center, The Institute of Medical Science The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2006.01.062"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29780"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602252"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32591\u20107"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26456"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.3923"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40257\u2010016\u20100238\u20109"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.32172"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.101136398"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/jjco\/hyy170"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13027"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2021.06.00"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472\u20106750\u20106\u201040"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cam.2.3.6353"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43856\u2010023\u201000270\u20104"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.CAN\u201005\u20102534"},{"issue":"1","key":"e_1_2_13_18_1","first-page":"153","article-title":"In Situ Expression of Soluble B7\u20101 in the Context of Oncolytic Herpes Simplex Virus Induces Potent Anti\u2010Tumor Immunity","volume":"61","author":"Todo T.","year":"2001","journal-title":"Cancer Research"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/258152a0"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/jitc\u20102020\u2010001486"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201031262\u2010y"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010022\u201001897\u2010x"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.27681"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1307935110"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3405"},{"issue":"21","key":"e_1_2_13_26_1","first-page":"5552","article-title":"Induction of Anti\u2010Tumor Immunity by Recombinant Vaccinia Viruses Expressing B7\u20101 or B7\u20102 Costimulatory Molecules","volume":"54","author":"Hodge J. W.","year":"1994","journal-title":"Cancer Research"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3300672"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365\u20102567.2000.00121.x"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u2010065X.2009.00770.x"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2017.07.006"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14754"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14340"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.omto.2021.05.004"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160062"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1074\u20107613(02)00362\u2010x"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010018\u20100044\u20100"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1586\/14737140.8.10.1581"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.10.003"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010019\u20100210\u2010z"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2013.220"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70410","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.70410","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.70410","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T14:10:15Z","timestamp":1788617415000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.70410"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":39,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1111\/cas.70410"],"URL":"https:\/\/doi.org\/10.1111\/cas.70410","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]},"assertion":[{"value":"2025-10-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}