Heat shock protein 72 expression allows permissive replication of oncolytic adenovirus dl1520 (ONYX-015) in rat glioblastoma cells
ONYX-015 (CI-1042), an adenovirus modified selectively to replicate in and kill cells that harbor p53 mutations, is under development by Onyx Pharmaceuticals for the potential treatment of various solid tumors, including head and neck, gastrointestinal and pancreatic tumors. It is a recombinant adenovirus that carries a loss-of-function mutation at the E1B locus, the product of which is a 55 kDa protein that binds to and inactivates the p53 tumor suppressor protein. Wild-type adenoviruses must disable this gene before viral replication can occur. This, the ONYX-015 adenovirus will leave normal cells unaffected. Mutations in the p53 tumor suppressor gene are the most common type of genetic abnormality in cancer, occurring in more than half of all major cancer types. Thus, these cells are susceptible to the virus, which will readily replicate and cause cell death. ONYX-015 is in ongoing phase III trials for the treatment of recurrent head and neck cancer, phase II trials for colorectal, ovary, pancreas and mouth tumors, and phase I trials for digestive disease, esophagus and liver tumors. Onyx Pharmaceuticals was granted US-05677178 covering methods for the treatment of p53-related cancers in October 1997. The patent specifically covers the use of modified adenoviruses and other DNA viruses, which lack viral proteins that bind to p53, for the treatment of cancer patients whose tumors lack p53 function. The USPTO awarded Onyx Pharmaceuticals US-05846945 in December 1998, covering methods for treating cancer using replicating adenoviral therapy in combination with chemotherapy. In April 1999, the company also received EP-094910177.8 covering the technology in Europe.