Cancer-killing viruses, also called “oncolytic” viruses, made their entry into oncology practices in 2015 with the approval of Amgen’s melanoma drug Imlygic, which was derived from herpes. Many other companies are studying a range of viruses as potential cancer remedies—but finding limited success so far.
Now a team of scientists led by the Ottawa Hospital Research Institute in Canada are proposing a new method for improving the ability of viruses to infect cancer cells. 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. They published their findings in the journal Science Translational Medicine.
The researchers studied vesicular stomatitis virus (VSV), which is being developed as a cancer drug, as is a related virus called Maraba. They 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, they reported. DMF also improved the performance of herpesvirus, Sindbis and adenovirus, they said.
Oncolytic viruses have been a challenge to develop because many patients seem to be resistant to their cancer-killing effects. VSV, for example, only works in about one-third of cancers, the Ottawa scientists point out in their paper. Amgen’s herpes-based viral treatment only extended survival by a few months over older melanoma treatments in its pivotal trial.
But the interest in testing combinations of cancer-killing viruses with other treatments remains strong. Last October, a phase 2 trial of Imlygic combined with Bristol-Myers Squibb’s CTLA4 inhibitor Yervoy doubled response rates in patients with advanced melanoma when compared to the BMS drug by itself. Earlier this month, researchers from the University of Ottawa and Ottawa Hospital announced they are seeing encouraging signs that Maraba is active against triple-negative breast cancer when deployed along with a checkpoint inhibitor.
Several new oncolytic viruses are under development—and they’re garnering support from Big Pharma. Last year, AbbVie nabbed an option on three such therapies being developed by Turnstone Biologics, including Ad-MG1-MAGEA3, derived from the Maraba virus. It’s being tested as a solo treatment and in combination with Merck’s immunotherapy drug Keytruda in people with solid tumors.
As for Tecfidera, its anticancer properties have 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.