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Hence, more effective strategies are needed urgently to modify therapeutic viruses to enhance their efficiency and safety in killing tumor cells and improve the survival rate of GBM patients. This study generated a new\u2010generation oncolytic adenovirus Ad5 KT\u2010E1A\u2010IL\u201015 (TS\u20102021) and evaluated its antitumor efficacy. Ex vivo analyses revealed Ki67 and TGF\u2010\u03b22 co\u2010localized in GBM cells. In addition, TS\u20102021 selectively replicated in GBM cells, which was dependent on the expression of Ki67 and TGF\u2010\u03b22. The immunocompetent mice model of GBM demonstrated the in vivo efficacy of TS\u20102021 by inhibiting tumor growth and improving survival proficiently. Notably, TS\u20102021 effectively reduced MMP3 expression by inactivating the MKK4\/JNK pathway, thereby reducing tumor invasiveness. Altogether, the findings of the present study highlight that TS\u20102021 can effectively target GBM cells expressing high levels of Ki67 and TGF\u2010\u03b22, exerting potent antitumor effects. Additionally, it can improve efficacy and suppress tumor invasiveness by inhibiting the MKK4\/JNK\/MMP3 pathway. Thus our study demonstrates the efficiency of the novel TS\u20102021 in the mouse model and provides a potential therapeutic option for patients with GBM.<\/jats:p>","DOI":"10.1002\/jmv.29335","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T10:16:15Z","timestamp":1703672175000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["TS\u20102021, a third\u2010generation oncolytic adenovirus that carried Ki67 promoter, TGF\u2010\u03b22 5\u2032UTR, and IL\u221215 against experimental glioblastoma"],"prefix":"10.1002","volume":"96","author":[{"given":"Jialin","family":"Wang","sequence":"first","affiliation":[{"name":"Brain Tumor Research Center, Beijing Neurosurgical Institute Capital Medical University  Beijing China"},{"name":"Department of Neurosurgery Beijing Tiantan Hospital Affiliated to Capital Medical University  Beijing China"},{"name":"Beijing Laboratory of Biomedical 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