Oncolytic Virus - Possible Applications

Possible Applications

Virus gene therapy has never been used successfully against cancer, mainly due to poor transduction of cells. This problem is solved by oncolytic viruses. The use of viral agents to treat cancer is now a real possibility, and several very promising advances have been made, e.g. ONYX-015 and MV-ERV. The most advanced oncolytic virus, based on herpes simplex is OncoVEX GM-CSF which is in Phase 3 clinical trials in melanoma and head and neck cancer. This virus has given a 20% complete response rate in melanoma, a level of efficacy which has never been seen by any agent in melanoma before.

Viral agents administered intravenously can be particularly effective against metastatic cancers, which are especially difficult to treat conventionally. However, blood-borne viruses can be deactivated by antibodies and cleared from the blood stream quickly e.g. by Kupffer cells (extremely active phagocytic cells in the liver, which are responsible for adenovirus clearance). Avoidance of the immune system until the tumour is destroyed could be the biggest obstacle to the success of oncolytic virus therapy. To date, no technique used to evade the immune system is entirely satisfactory. It is in conjunction with conventional cancer therapies that oncolytic viruses have often showed the most promise, since combined therapies operate synergistically with no apparent negative effects. An exception to each of these points is again provided by OncoVEX GM-CSF (BioVex Inc, Woburn MA), the efficacy of which has been found not to be compromised by host immunity, and with which stand alone therapy has provided an approximately 30% response rate (PR + CR) against systemic disease, following local injection into accessible tumors. This is because this virus stimulates a systemic anti-tumor immune response enhanced through the expression of GM-CSF in the dying tumor micro-environment. OncoVEX GM-CSF is currently completing a pivotal Phase 3 trial in melanoma, the first pivotal trial with an oncolytic virus to ever be conducted, and a phase 3 trial in head and neck cancer is also underway. (The developer of OncoVEX GM-CSF, BioVex Inc, was purchased by Amgen for $1 billion in January 2011.)

The specificity and flexibility of oncolytic viruses means they have the potential to treat a wide range of cancers with minimal side effects. However, altering the host range or tissue specificity of any virus has significant safety implications.