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Ad[CE1A] infection, replication, and oncolysis were assessed in a panel of myeloma cell lines (n\u2009=\u20098) and ex vivo samples from myeloma patients (n\u2009=\u200917) and healthy donors (HDs) (n\u2009=\u200914). Ad[CE1A] efficiently infected, replicated, and induced oncolysis in myeloma cells, but not in control cell lines or HDs, demonstrating selective cytotoxicity. Mechanistic studies revealed Ad[CE1A]-induced cell death is caspase-independent, with a potential involvement of necroptosis. Ad[CE1A] also altered immunogenic cell death markers (calreticulin, CD47, extracellular ATP), enhanced antigen presentation via increased MHC class I and II receptor expression (HLA-ABC and HLA-DR), and stimulated bystander cytokine killing, indicating potential for direct and immune-mediated anti-myeloma responses. In vivo experiments with 5TGM1 syngeneic and U266 xenograft models showed Ad[CE1A] significantly reduced myeloma tumor burden compared to vehicle control. Combination therapy with anti-myeloma drugs, bortezomib, melphalan, panobinostat and pomalidomide, enhanced Ad[CE1A] efficacy, with melphalan upregulating <jats:italic>SLAMF7<\/jats:italic>, resulting in increased viral replication. In summary, these findings support Ad[CE1A] as a promising myeloma therapy.<\/jats:p>","DOI":"10.1038\/s41375-025-02617-3","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T18:32:59Z","timestamp":1744914779000},"page":"1449-1463","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["An oncolytic adenovirus targeting SLAMF7 demonstrates anti-myeloma efficacy"],"prefix":"10.1038","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7397-2132","authenticated-orcid":false,"given":"Georgia","family":"Stewart","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Tazzyman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yidan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0911-4250","authenticated-orcid":false,"given":"Rebecca E.","family":"Andrews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren","family":"Lath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Down","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7162-8151","authenticated-orcid":false,"given":"Georgia","family":"Robinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munitta","family":"Muthana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew. 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