Onyx-015 is an experimental oncolytic virus created by genetically engineering an adenovirus. It has been trialed as a possible treatment for cancer. The E1B-55kDa gene has been deleted allowing the virus to selectively replicate in and lyse p53-deficient cancer cells.
Tumours form in cells when mutations in genes involved in cell cycle control and apoptosis accumulate over time. Most tumours studied, have defects in the p53 tumor suppressor pathway. p53 is a transcription factor that plays a role in apoptosis, cell cycle and DNA repair. It blocks cell progression in response to cellular stress or DNA damage. Many viruses replicate by altering the cell cycle and exploiting the same pathways that are altered in cancer cells. E1B proteins produced by adenoviruses protect the infected cell by binding to and degrading the p53 transcription factors, preventing it from targeting the cell for apoptosis. This allows the virus to replicate, package its genome, lyse the cell and spread to new cells.
This gave rise to the idea that an altered adenovirus could be used to target and eliminate cancer cells. Onyx-015 is a adenovirus that was developed in 1987 with the function of the E1B gene knocked out, meaning cells infected with Onyx-015 are incapable of blocking p53's function. If Onyx-015 infects a normal cell, with a functioning p53 gene, it will be prevented from multiplying by the action of the p53 transcription factor. However if Onyx-015 infects a p53 deficient cell it should be able to survive and replicate, resulting in selective destruction of cancer cells.
The patent for ONYX-015 was held by ONYX Pharmaceuticals and it was used in combination with the standard chemotherapeutic agents cisplatin and 5-fluorouracil to combat head and neck tumours. Onyx-015 has been extensively tested in clinical trials, with the data indicating that it is safe and selective for cancer. However, limited therapeutic effect has been demonstrated following injection and systemic spread of the virus was not detected. Further development of Onyx-015 was abandoned in the early 2000s, the rights being sold to the Chinese company, Shanghai Sunway Biotech. On November 17, 2005, the Chinese State Food and Drug Administration approved H101, an oncolytic adenovirus similar to Onyx-015 (E1B-55K/E3B-deleted), for use in combination with chemotherapy for the treatment of late-stage refractory nasopharyngeal cancer.
- ^ Definition of ONYX-015 - National Cancer Institute Drug Dictionary
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