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Among various oncolytic viruses, adenoviruses (HAdVs) have been extensively studied due to their ability to be genetically modified for enhanced tumor selectivity and immunogenicity. This review explores the mechanisms by which adenovirus vectors function as cancer immunotherapies, detailing their genetic modifications to improve tumor targeting, replication, and immune activation. Additionally, we highlight key clinical trials that have evaluated adenovirus-based therapies in different cancer types, emphasizing their efficacy, safety, and potential for future therapeutic applications.<\/jats:p>","DOI":"10.3389\/fonc.2026.1824087","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T04:23:43Z","timestamp":1783916623000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Recombinant adenoviruses application for cancer vaccines: from genetic design to clinical translation"],"prefix":"10.3389","volume":"16","author":[{"given":"Nada A.","family":"Almarghalani","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Faculty of Science, King Abdulaziz University","place":["Jeddah, Saudi Arabia"]},{"name":"Immunology Research Program, King Abdullah International Medical Research Center","place":["Jeddah, Saudi Arabia"]},{"name":"Health and Life 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