Two phase II trials evaluated the virus in patients with recurrent head and neck cancer, after intratumoral injections. The initial trials tested the efficacy of the ONYX-015 as a single agent. The maximum tolerated dose has not been reached after intratumoral, hepatic artery, intraperitoneal, or systemic administration of the virus ( 8, 10– 12). The virus has demonstrated a remarkable safety profile, independent of the route of administration. In 1996, ONYX-015 was the first oncolytic virus to enter human clinical trials ( 9). This can at least in part be explained by p53 inactivation due to other mechanisms, such as mdm2 amplification ( 7, 8). Subsequent work, however, has shown that ONYX-015 can grow efficiently in cancer cells with wild-type p53 ( 5, 6). resistance, this could represent an attractive approach in the treatment of cancer ( 3, 4). Because approximately 50% of human cancers have p53 mutations, and these are often associated with chemotherapy. This interaction causes p53 to be degraded and prevents it from causing cell cycle arrest, thus leading to a productive viral infection. The E1B protein in conjunction with E4ORF6 binds to the tumor suppressor protein p53 ( 2). ONYX-015 (dl1520) is chimeric human group C adenovirus that has been genetically engineered to incorporate deletions in the E1B-55k and E3B regions ( 1).