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There have been no major changes in patient survival in the past four decades. Therefore, new therapeutic interventions are needed. We have developed an enhanced conditionally replicative canine oncolytic adenovirus, CAV2-AU-M3, armed with an anti-PD1 heavy-chain antibody (HcAb), and evaluated its efficacy against osteosarcoma across four canine cell lines. CAV2-AU-M3 was characterized for its infectivity, lytic properties, and anti-PD1 Ab production in monolayer and spheroid cultures. Additionally, the impact of intratumoral administration of the virus on tumor growth was measured in a mouse model. Our study demonstrates that CAV2-AU-M3 infects and lyses different canine OS cell lines at varying rates but produces anti-PD1 Ab at similar levels across all osteosarcoma cell lines. Additionally, anti-PD1 Ab produced by CAV2-AU-M3 can effectively bind the cell surface PD1 receptor and inhibit the binding of PDL1 to PD1 receptors.<\/jats:p>","DOI":"10.1007\/s00262-026-04458-0","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T10:15:37Z","timestamp":1781950537000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Oncolytic virus with an immune stimulatory payload for osteosarcoma therapy"],"prefix":"10.1007","volume":"75","author":[{"given":"Sumbul","family":"Khan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa A.","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabella","family":"Shimko-Lofano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maninder","family":"Sandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Logsdon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gracie","family":"Bunch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasin","family":"Fatemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leah M. 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