Mechanism of action of Reolysin

Reolysin? (Oncolytics Biotech, Calgary, AB, Canada), is a proprietary variant of the reovirus, an acronym for Respiratory Enteric Orphan Virus or reovirus. Reovirus is a common, benign, virus that does not cause any disease symptoms. However, ongoing research has shown that this virus can kill cancer cells, but does not harm normal, healthy, cells. 

Reolysin is currently in late stage Phase III clinical trials in head and neck cancers and has been included in nearly thirty clinical trials including translational, Phase I, Phase II (both single arm and randomized), and Phase III studies in a broad range of cancer indications. Overall, the trial drug has shown to be well-tolerated, with patients exhibiting only mild, flu-like symptoms.

Mechanism of action
Reolysin has been formulated to replicate specifically in tumor cells that bear an activated RAS pathway. These cells are deficient in their ability to activate a natural anti-viral response as mediated by protein kinase RNA-activated or protein kinase R (PKR) activity, which is present in normal cells but absent in tumor cells with activated RAS pathways (normal cells do not possess activated RAS pathways). PKR, an enzyme that lies dormant until it detects viruses replicating within a cell, is one of the immune system?s strongest cellular defenses. Once active, PKR is able to phosphorylate the Eukaryotic translation initiation factor 2A or EIF2A, which inhibits cellular mRNA translation and subsequent viral protein synthesis. Through complex mechanisms, active PKR is also able to induce cellular apoptosis which prevents further viral spread. In this process, as tumor cells die, the progeny viral particles spread to neighboring cells, a process which in turn triggers the continuous cycle of infection, replication and cell death. This cellular cycle of viral oncolysis is involved in ?educating ? the immune system to recognize and kill similar tumor cells, blocking nearly all protein production in the cell to prevent virus replication, stopping only when the virus is eradicated by treatment or cell death.

Animation of Reolysin in combination with Chemoherapy

Reolysin is not licensed for use by the U.S. Food and Drug Administration (FDA) or European Medicines Agency (EMA) and is only available in clinical trials. The trial drug is currently being manufactured under a commercial supply agreement between Oncolytics Biotech and SAFC, a Division of Sigma-Aldrich Corporation.

For more information:
A systematic approach to improve productivity and increase regulatory compliance for a vaccine (SAFC; Vaccine Manufacturing, Case Study);
– Experience peace of mind in your vaccine manufacturing process (SAFC);
– Patient Enrollment Completed in Phase I Trial Investigating Reolysin? in Combination with FOLFIRI in Patients with Colorectal Cancer, Onco’Zine; August 16, 2012;
– Oncolytics Biotech and NCIC CTG Sign Agreement for Randomized Phase II Study in Colorectal Cancer, Onco’Zine; May 3, 2012;
REO 017 Meets Primary Endpoint for First Part of U.S. Phase II Pancreatic Cancer Clinical Trial, Onco’Zine; February 14, 2011;
Randomized Phase II Ovarian Cancer Study With Reolysin? To Be Conducted By The Gynecologic Oncology Group (GOG), Onco’Zine; September 2, 2010.

Last update August 19, 2012