{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T12:19:09Z","timestamp":1762431549649,"version":"3.41.2"},"reference-count":23,"publisher":"Wiley","issue":"2-3","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>A549 carrier cells infected with oncolytic adenovirus can induce complete tumor reduction of subcutaneous ovarian tumors but not intraperitoneal disseminated ovarian tumors. This appears to be a result of the insufficient antitumor effect of A549 carrier cells. Therefore, in the present study, we cloned a novel carrier cell with the aim of improving the antitumor effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Carrier cells infected with oncolytic adenovirus AdE3\u2010<jats:italic>midkine<\/jats:italic> with a <jats:italic>midkine<\/jats:italic> promoter were cloned by limiting dilution. We examined the antitumor effects of these cells on subcutaneous and intraperitoneal OVHM ovarian tumors in a syngeneic mouse model. Biosafety tests were conducted in beagle dogs and rabbits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We cloned EHMK\u201051\u201035 carrier cells with 10\u2010fold higher antitumor effects compared to A549 carrier cells <jats:italic>in vitro<\/jats:italic>. EHMK\u201051\u201035 carrier cells co\u2010infected with AdE3\u2010<jats:italic>midkine<\/jats:italic> and Ad\u2010<jats:italic>mGM\u2010CSF<\/jats:italic> induced a 100% complete tumor reduction in subcutaneous tumors and a 60% reduction of intraperitoneal disseminated tumors. Single\u2010dose acute toxicity test on beagle dogs with EHMK\u201051\u201035 carrier cells co\u2010infected with AdE3\u2010<jats:italic>midkine<\/jats:italic> and Ad\u2010<jats:italic>cGM\u2010CSF<\/jats:italic> showed no serious side effects. Biologically active adenoviruses were not detected in the blood, saliva, feces, urine or whole organs. In a chronic toxicity test, VX2 tumors in rabbits were injected five times with EHMK\u201051\u201035 carrier cells infected with AdE3\u2010<jats:italic>midkine<\/jats:italic> and these rabbits showed no serious side effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Significant antitumor effects and safety of cloned EHMK\u201051\u201035 carrier cells were confirmed in intraperitoneal ovarian tumors and toxicity tests, respectively. These findings will be extended to preclinical efficacy studies using dogs and cats, with the aim of conducting human clinical trials on refractory solid tumors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3064","type":"journal-article","created":{"date-parts":[[2018,12,14]],"date-time":"2018-12-14T00:19:17Z","timestamp":1544746757000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cloning of carrier cells infected with oncolytic adenovirus driven by <i>midkine<\/i> promoter and biosafety studies"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4954-3992","authenticated-orcid":false,"given":"Katsuyuki","family":"Hamada","sequence":"first","affiliation":[{"name":"Department of Clinical Oncology, School of Medicine Toho University  Tokyo Japan"},{"name":"Department of Obstetrics and Gynecology, School of Medicine Ehime University  Ehime Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soichi","family":"Takagi","sequence":"additional","affiliation":[{"name":"Advanced Biomedical Engineering and Science, Graduate School of Medicine Tokyo Women's Medical University  Tokyo Japan"},{"name":"Animal Stem Cell Inc.  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