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Oncolytic virus replication is an immunogenic phenomenon, and viruses can be armed with immunostimulatory molecules. Therefore, oncolytic immuno\u2010virotherapy of malignant melanoma is an appealing approach, which was recently validated by a positive phase 3 trial. We investigated the potency of oncolytic adenovirus Ad5\/3\u2010D24\u2010GMCSF on a panel of melanoma cell lines and animal models, and summarized the melanoma\u2010specific human data from the Advanced Therapy Access Program (ATAP). The virus effectively eradicated human melanoma cells <jats:italic>in vitro<\/jats:italic> and subcutaneous SK\u2010MEL\u201028 melanoma xenografts in nude mice when combined with low\u2010dose cyclophosphamide. Furthermore, virally\u2010expressed granulocyte\u2010macrophage colony\u2010stimulating factor (GM\u2010CSF) stimulated the differentiation of human monocytes into macrophages. In contrast to human cells, RPMI 1846 hamster melanoma cells exhibited no response to oncolytic viruses and the chimeric 5\/3 fiber failed to increase the efficacy of transduction, suggesting limited utility of the hamster model in the context of viruses with this capsid. In ATAP, treatments appeared safe and well\u2010tolerated. Four out of nine melanoma patients treated were evaluable for possible therapy benefit with modified RECIST criteria: one patient had minor response, two had stable disease, and one had progressive disease. Two patients were alive at 559 and 2,149 days after treatment. Ad5\/3\u2010D24\u2010GMCSF showed promising efficacy in preclinical studies and possible antitumor activity in melanoma patients refractory to other forms of therapy. This data supports continuing the clinical development of oncolytic adenoviruses for treatment of malignant melanoma.<\/jats:p>","DOI":"10.1002\/ijc.29536","type":"journal-article","created":{"date-parts":[[2015,3,27]],"date-time":"2015-03-27T22:07:47Z","timestamp":1427494067000},"page":"1775-1783","source":"Crossref","is-referenced-by-count":45,"title":["Treatment of melanoma with a serotype 5\/3 chimeric oncolytic adenovirus coding for GM\u2010CSF: <scp>R<\/scp>esults <i>in vitro<\/i>, in rodents and in humans"],"prefix":"10.1002","volume":"137","author":[{"given":"Simona","family":"Bramante","sequence":"first","affiliation":[{"name":"Cancer Gene Therapy Group Department of Pathology and Transplantation Laboratory and Haartman Institute University of Helsinki  Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johanna K.","family":"Kaufmann","sequence":"additional","affiliation":[{"name":"Oncolytic Adenovirus Group German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]) Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ville","family":"Veckman","sequence":"additional","affiliation":[{"name":"Unit of Systems Toxicology Finnish Institute of Occupational Health Topeliuksenkatu 41 a Helsinki Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilkka","family":"Liikanen","sequence":"additional","affiliation":[{"name":"Cancer Gene Therapy Group Department of Pathology and Transplantation Laboratory and Haartman Institute University of Helsinki  Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dirk M.","family":"Nettelbeck","sequence":"additional","affiliation":[{"name":"Oncolytic Adenovirus Group German Cancer Research Center (Deutsches Krebsforschungszentrum [DKFZ]) Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Otto","family":"Hemminki","sequence":"additional","affiliation":[{"name":"Cancer Gene Therapy Group Department of Pathology and Transplantation Laboratory and Haartman Institute University of Helsinki  Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lotta","family":"Vassilev","sequence":"additional","affiliation":[{"name":"Oncos Therapeutics Ltd. 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