Biogen’s MS drug Potentiates Oncolytic Viruses In Fight Against Cancer
Oncolytic viruses are a promising anti-cancer platform, achieving significant pre-clinical and clinical milestones in recent years. They offer the attractive therapeutic combination of tumor-specific cell lysis together with immune stimulation, therefore acting as potential in situ tumor vaccines. Moreover, OVs can be engineered for optimization of tumor selectivity and enhanced immune stimulation and can be readily combined with other agents.
However, these viruses need to reach tumor cells and get inside them to achieve a therapeutic effect, and this does not always happen.
Now, a bunch of scientists at the Ottawa Hospital Research Institute in Canada have identified a promising solution for this problem by combining oncolytic vesicular stomatitis virus (VSV) with dimethyl fumarate, a small-molecule drug that is already in use for some nonmalignant disorders and may also have direct anticancer effects.
They have preliminary evidence that dimethyl fumarate (DMF), which is marketed by Biogen as Tecfidera to treat multiple sclerosis, boosts the potency of oncolytic viruses.
In the course of their research, the team tested the effect of a DMF-VSV combo on several cancer cell lines, including renal carcinoma, osteosarcoma and melanoma. When they administered DMF to the
renal carcinoma cells four hours prior to giving them VSV, they found the virus grew by more than 100-fold.DMF also improved the performance of herpesvirus, Sindbis and adenovirus, they report.
Tecfidera’s anticancer properties have already been well documented, and the drug is currently being tested to treat chronic lymphocytic leukemia and cutaneous T cell lymphoma.
The Ottawa team wanted to understand why the MS drug enhances cancer-killing viruses, so they studied gene-expression patterns on cancer cells infected with VSF, both with and without DMF and related drugs. They discovered that VSF ramps up the activity of antiviral genes—but that DMF inhibits those genes.
Strong evidence that Tecfidera is safe, coupled with the availability of both marketed and investigational oncolytic viruses, should provide “a clear path toward clinical evaluation of this promising combination therapy,” the authors of the new study argued.
