Big Pharma companies active in the immuno-oncology field have recognized the potential clinical and commercial value of oncolytic viruses, according to a report from La Merie Publishing of Stuttgart, Germany. In the short term, the combination of an oncolytic virus with an immune checkpoint inhibitor represents a path toward quick regulatory approval, the report says. Amgen and Merck are in the lead with a pivotal phase 3 combination trial.
Early clinical data indicated synergistic efficacy without increased toxicity when oncolytic viruses were combined with immune checkpoint inhibitors. In addition to direct cancer cell lysis, oncolytic viruses induce a tumor-specific systemic immunity, which can be enhanced by checkpoint inhibitors.
The acquisition of the oncolytic virus company BioVex by Amgen in 2011 was a “game changer” for the field of oncolytic viruses, according to the report. The approval of the herpes simplex oncolytic virus Imlygic (Amgen) in 2015 further strengthened this trend. Pharma companies have increasingly recognized that oncolytic viruses not only could directly lyse cancer cells, but also “freed” tumor-specific neoantigens, thereby indirectly acting as a cancer vaccine.
The next-generation constructs of oncolytic viruses currently in development incorporate transgenes to locally express immune system co-stimulatory molecules, such as 4-1BB, CD40L, OX40, and CD80, as well as CD3 receptors, to recruit T cells or single-chain antibodies for local anti-programmed death-1 (PD-1) activity. If proven effective in clinical trials, oncolytic viruses could become stand-alone therapeutics and could compete with immuno-oncology compounds and cancer vaccines, the report predicts.