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However, these trials also revealed the disadvantages of the systemic toxicity of IFN and insufficient delivery of IFN. To improve efficacy and tolerability, we have developed an oncolytic adenovirus\u2010expressing IFN (IFN\u2010OAd). Here, we evaluated IFN\u2010OAd in combination with chemotherapy (gemcitabine\u2009+\u2009nab\u2010paclitaxel)\u2009+\u2009radiation. Combination index (CI) analysis showed that IFN\u2010OAd\u2009+\u2009chemotherapy\u2009+\u2009radiation was synergistic (CI\u2009&lt;1). Notably, IFN\u2010OAd\u2009+\u2009chemotherapy\u2009+\u2009radiation remarkably suppressed tumor growth and induced a higher number of tumor\u2010infiltrating lymphocytes without severe side toxic effects in an immunocompetent and adenovirus replication\u2010permissive hamster PDAC model. This is the first study to report that gemcitabine\u2009+\u2009nab\u2010paclitaxel, the current first\u2010line chemotherapy for PDAC, did not hamper virus replication in a replication\u2010permissive immunocompetent model. IFN\u2010OAd has the potential to overcome the barriers to clinical application of IFN\u2010based therapy through its tumor\u2010specific expression of IFN, induction of antitumor immunity, and sensitization with chemoradiation. Combining IFN\u2010OAd with gemcitabine\u2009+\u2009nab\u2010paclitaxel\u2009+\u2009radiation might be an effective and clinically beneficial treatment for PDAC patients.<\/jats:p>","DOI":"10.1111\/cas.15903","type":"journal-article","created":{"date-parts":[[2023,7,13]],"date-time":"2023-07-13T07:11:25Z","timestamp":1689232285000},"page":"3759-3769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Interferon\u2010expressing oncolytic adenovirus\u2009+\u2009chemoradiation inhibited pancreatic cancer growth in a hamster model"],"prefix":"10.1111","volume":"114","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4128-2177","authenticated-orcid":false,"given":"Shuhei","family":"Shinoda","sequence":"first","affiliation":[{"name":"Department of Surgery University of Minnesota  Minneapolis MN USA"},{"name":"Department of Gastroenterology and Hepatology Yamaguchi University Graduate school of Medicine  Yamaguchi 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