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Our aim was to study the efficacy of VSV\u2010GP, a vesicular stomatitis virus carrying the glycoprotein of lymphocytic choriomeningitis virus, against prostate cancer, for which current treatment options still fail to cure metastatic disease. VSV\u2010GP was found to infect 6 of 7 prostate cancer cell lines with great efficacy. However, susceptibility was reduced in one cell line with low virus receptor expression and in 3 cell lines after interferon alpha treatment. Four cell lines had developed resistance to interferon type I at different levels of the interferon signaling pathway, resulting in a deficient antiviral response. In prostate cancer mouse models, long\u2010term remission was achieved upon intratumoral and, remarkably, also upon intravenous treatment of subcutaneous tumors and bone metastases. 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