{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T10:21:52Z","timestamp":1788517312313,"version":"build-2803163510"},"reference-count":32,"publisher":"SAGE Publications","issue":"3-4","license":[{"start":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T00:00:00Z","timestamp":1768262400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82573748"],"award-info":[{"award-number":["82573748"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,2,1]]},"abstract":"<jats:p>\n                    The adenovirus\n                    <jats:italic toggle=\"yes\">E3<\/jats:italic>\n                    region\u2019s immune-modulating genes (\n                    <jats:italic toggle=\"yes\">gp19K<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Adenovirus Death Protein [ADP]<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">E3B<\/jats:italic>\n                    ) are frequently modified in oncolytic adenoviruses (OAds) through deletion and transgene insertion like granulocyte-macrophage colony-stimulating factor (\n                    <jats:italic toggle=\"yes\">GM-CSF<\/jats:italic>\n                    ). However, the synergistic effects of dual-gene deletions on antitumor efficacy and transgene capacity remain unexplored. To address this, we constructed three E3-modified OAds including OAd5-delgp19K (del\n                    <jats:italic toggle=\"yes\">gp19K<\/jats:italic>\n                    ), M20 (del\n                    <jats:italic toggle=\"yes\">gp19K<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">ADP<\/jats:italic>\n                    ), M22-0 (del\n                    <jats:italic toggle=\"yes\">gp19K<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">E3B<\/jats:italic>\n                    ), and their\n                    <jats:italic toggle=\"yes\">GM-CSF<\/jats:italic>\n                    -armed derivatives, systematically evaluating the impact of\n                    <jats:italic toggle=\"yes\">ADP<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">E3B<\/jats:italic>\n                    deletions on viral replication, tumor cell lysis, immune modulation, and\n                    <jats:italic toggle=\"yes\">in\u00a0vivo<\/jats:italic>\n                    antitumor activity. Key findings revealed that\n                    <jats:italic toggle=\"yes\">gp19K\/ADP<\/jats:italic>\n                    deletion OAd prolonged intracellular viral replication, creating a \u201cviral bomb\u201d effect that delayed cell lysis, evading anti-adenovirus antibodies, sustained GM-CSF expression, and culminating in superior tumor suppression.\n                    <jats:italic toggle=\"yes\">Gp19K\/E3B<\/jats:italic>\n                    deletion OAd accelerated viral dissemination but triggered rapid antibody-mediated clearance in immunocompetent hosts, resulting in transient GM-CSF expression and diminished therapeutic persistence. In immunocompetent Syrian hamster Hap-T1 subcutaneous tumor models,\n                    <jats:italic toggle=\"yes\">gp19K\/ADP<\/jats:italic>\n                    deletion OAd demonstrated potent tumor inhibition, durable immune microenvironment remodeling, robust viral replication, and evading anti-adenovirus antibodies. These results underscore the critical role of coordinated\n                    <jats:italic toggle=\"yes\">gp19K\/ADP<\/jats:italic>\n                    deletion in optimizing viral replication, transgene expression, and immune evasion, providing a strategic framework for engineering next-generation OAds.\n                  <\/jats:p>","DOI":"10.1177\/10430342251411042","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T05:15:43Z","timestamp":1768367743000},"page":"102-113","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeted E3 Region Engineering Boosts Antitumor Efficacy of Conditionally Replicating Adenoviruses in an Immunocompetent Tumor Model"],"prefix":"10.1177","volume":"37","author":[{"given":"Yao","family":"Si","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengfeng","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry of Education), Hubei Key Laboratory of Tumor Invasion and Metastasis, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Key Laboratory of Cancer Invasion and Metastasis (Ministry 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