{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T12:09:52Z","timestamp":1785931792566,"version":"3.56.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22ck0106569h0003"],"award-info":[{"award-number":["JP22ck0106569h0003"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-22389-1","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:57:37Z","timestamp":1762282657000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Serum extracellular vesicles containing adenoviral E1A-DNA as a predictive biomarker for liquid biopsy in oncolytic adenovirus therapy"],"prefix":"10.1038","volume":"15","author":[{"given":"Chiaki","family":"Yagi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4484-1253","authenticated-orcid":false,"given":"Shinji","family":"Kuroda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiko","family":"Kakiuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunya","family":"Hanzawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Kadowaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Hamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoma","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Ohtani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kento","family":"Kumon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuhiko","family":"Kanaya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Kikuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunsuke","family":"Kagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tazawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuo","family":"Urata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiyoshi","family":"Fujiwara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"22389_CR1","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/nrclinonc.2013.110","volume":"10","author":"E Crowley","year":"2013","unstructured":"Crowley, E., Di Nicolantonio, F., Loupakis, F. & Bardelli, A. Liquid biopsy: monitoring cancer-genetics in the blood. Nat. Rev. Clin. Oncol. 10, 472\u2013484 (2013).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"22389_CR2","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1186\/s13045-022-01351-y","volume":"15","author":"M Nikanjam","year":"2022","unstructured":"Nikanjam, M., Kato, S. & Kurzrock, R. Liquid biopsy: current technology and clinical applications. J. Hematol. Oncol. 15, 131 (2022).","journal-title":"J. Hematol. Oncol."},{"key":"22389_CR3","doi-asserted-by":"publisher","first-page":"2359","DOI":"10.1056\/NEJMcibr1503100","volume":"372","author":"L O\u2019Driscoll","year":"2015","unstructured":"O\u2019Driscoll, L. Expanding on exosomes and ectosomes in cancer. N Engl. J. Med. 372, 2359\u20132362 (2015).","journal-title":"N Engl. J. Med."},{"key":"22389_CR4","doi-asserted-by":"publisher","first-page":"766","DOI":"10.1038\/cr.2014.44","volume":"24","author":"BK Thakur","year":"2014","unstructured":"Thakur, B. K. et al. Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell. Res. 24, 766\u2013769 (2014).","journal-title":"Cell. Res."},{"key":"22389_CR5","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1016\/j.cell.2020.07.009","volume":"182","author":"A Hoshino","year":"2020","unstructured":"Hoshino, A. et al. Extracellular vesicle and particle biomarkers define multiple human cancers. Cell 182, 1044\u20131061e1018 (2020).","journal-title":"Cell"},{"key":"22389_CR6","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12943-022-01509-9","volume":"21","author":"D Yu","year":"2022","unstructured":"Yu, D. et al. Exosomes as a new frontier of cancer liquid biopsy. Mol. Cancer. 21, 56 (2022).","journal-title":"Mol. Cancer"},{"key":"22389_CR7","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.jcmgh.2016.10.003","volume":"3","author":"T Sanada","year":"2017","unstructured":"Sanada, T. et al. Transmission of HBV DNA mediated by Ceramide-Triggered extracellular vesicles. Cell. Mol. Gastroenterol. Hepatol. 3, 272\u2013283 (2017).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"22389_CR8","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/s41571-022-00719-w","volume":"20","author":"SZ Shalhout","year":"2023","unstructured":"Shalhout, S. Z., Miller, D. M., Emerick, K. S. & Kaufman, H. L. Therapy with oncolytic viruses: progress and challenges. Nat. Rev. Clin. Oncol. 20, 160\u2013177 (2023).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"22389_CR9","doi-asserted-by":"publisher","first-page":"2780","DOI":"10.1200\/JCO.2014.58.3377","volume":"33","author":"RH Andtbacka","year":"2015","unstructured":"Andtbacka, R. H. et al. Talimogene Laherparepvec improves durable response rate in patients with advanced melanoma. J. Clin. Oncol. 33, 2780\u20132788 (2015).","journal-title":"J. Clin. Oncol."},{"key":"22389_CR10","doi-asserted-by":"publisher","first-page":"1630","DOI":"10.1038\/s41591-022-01897-x","volume":"28","author":"T Todo","year":"2022","unstructured":"Todo, T. et al. Intratumoral oncolytic herpes virus G47\u2206 for residual or recurrent glioblastoma: a phase 2 trial. Nat. Med. 28, 1630\u20131639 (2022).","journal-title":"Nat. Med."},{"key":"22389_CR11","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1158\/1078-0432.CCR-1075-3","volume":"10","author":"T Kawashima","year":"2004","unstructured":"Kawashima, T. et al. Telomerase-specific replication-selective virotherapy for human cancer. Clin. Cancer Res. 10, 285\u2013292 (2004).","journal-title":"Clin. Cancer Res."},{"key":"22389_CR12","doi-asserted-by":"publisher","first-page":"9339","DOI":"10.1158\/0008-5472.CAN-10-2333","volume":"70","author":"S Kuroda","year":"2010","unstructured":"Kuroda, S. et al. Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via Inhibition of DNA repair machinery. Cancer Res. 70, 9339\u20139348 (2010).","journal-title":"Cancer Res."},{"key":"22389_CR13","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.ymthe.2020.01.003","volume":"28","author":"N Kanaya","year":"2020","unstructured":"Kanaya, N. et al. Immune modulation by Telomerase-Specific oncolytic adenovirus synergistically enhances antitumor efficacy with Anti-PD1 antibody. Mol. Ther. 28, 794\u2013804 (2020).","journal-title":"Mol. Ther."},{"key":"22389_CR14","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/ags3.12270","volume":"3","author":"T Fujiwara","year":"2019","unstructured":"Fujiwara, T. Multidisciplinary oncolytic virotherapy for Gastrointestinal cancer. Ann. Gastroenterol. Surg. 3, 396\u2013404 (2019).","journal-title":"Ann. Gastroenterol. Surg."},{"key":"22389_CR15","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1038\/mt.2009.262","volume":"18","author":"J Nemunaitis","year":"2010","unstructured":"Nemunaitis, J. et al. A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Mol. Ther. 18, 429\u2013434 (2010).","journal-title":"Mol. Ther."},{"key":"22389_CR16","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.ejca.2021.04.043","volume":"153","author":"Y Shirakawa","year":"2021","unstructured":"Shirakawa, Y. et al. Phase I dose-escalation study of endoscopic intratumoral injection of OBP-301 (Telomelysin) with radiotherapy in oesophageal cancer patients unfit for standard treatments. Eur. J. Cancer. 153, 98\u2013108 (2021).","journal-title":"Eur. J. Cancer"},{"key":"22389_CR17","doi-asserted-by":"publisher","first-page":"2920","DOI":"10.1016\/j.ymthe.2021.05.015","volume":"29","author":"Y Kakiuchi","year":"2021","unstructured":"Kakiuchi, Y. et al. Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles. Mol. Ther. 29, 2920\u20132930 (2021).","journal-title":"Mol. Ther."},{"key":"22389_CR18","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1080\/14728222.2023.2259102","volume":"27","author":"Y Kakiuchi","year":"2023","unstructured":"Kakiuchi, Y. et al. Exosomes as a drug delivery tool for cancer therapy: a new era for existing drugs and oncolytic viruses. Expert Opin. Ther. Targets. 27, 807\u2013816 (2023).","journal-title":"Expert Opin. Ther. Targets"},{"key":"22389_CR19","doi-asserted-by":"publisher","first-page":"113480","DOI":"10.1016\/j.biopha.2022.113480","volume":"153","author":"Z Wang","year":"2022","unstructured":"Wang, Z., Mo, H., He, Z., Chen, A. & Cheng, P. Extracellular vesicles as an emerging drug delivery system for cancer treatment: current strategies and recent advances. Biomed. Pharmacother. 153, 113480 (2022).","journal-title":"Biomed. Pharmacother"},{"key":"22389_CR20","doi-asserted-by":"crossref","unstructured":"Kalluri, R. & LeBleu, V. S. The biology, function, and biomedical applications of exosomes. Science 367 (2020).","DOI":"10.1126\/science.aau6977"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22389-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22389-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22389-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:57:38Z","timestamp":1762282658000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-22389-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["22389"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-22389-1","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-7034375\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]},"assertion":[{"value":"3 July 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Yasuo Urata is the President and CEO of Oncolys BioPharma, Inc., the manufacturer of OBP-301, OBP-401, and OBP-502. Hiroshi Tazawa and Toshiyoshi Fujiwara are consultants for Oncolys BioPharma, Inc. The remaining authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"38590"}}