Compositions including attenuated oncolytic viruses and methods of their use for the treatment of cancer are disclosed. Some attenuated virus exhibit potential as tumor therapies by exhibiting characteristics such as high selectivity, infectivity, cytotoxicity, or replication index for tumor cells, and/or low infectivity, cytotoxicity, or replication index for normal cells. In preferred embodiments, the ratio of replication of virus in normal cells:tumor cells is about 1:100 or greater. Preferred viruses have two or more mechanisms of attenuation including insertion of a transgene such as GFP or an interferon, preferably at position 1 of the viral genome. The compositions can be administered to subjects having tumors, in an effective amount to delay or inhibit the growth of a tumor, reduce the growth or size of the tumor, and/or inhibit or reduce metastasis of the tumor. Methods for manufacturing viruses and methods of testing their oncolytic potential are also disclosed.
