Early clinical readouts for next-generation oncolytic viruses are hinting at high efficacy when combined with checkpoint inhibitors, and pharmas are off to the races to find the best pairings.
After more than two decades of development, oncolytic viruses have yielded little clinical efficacy, partly because companies haven’t fully understood or exploited modality, and partly because safety concerns led them to start cautiously with attenuated viruses.
However, a newly uncovered immune-stimulating mechanism for oncolytic viruses and growing demand for agents that synergize with checkpoint inhibitors have triggered a resurgence of interest.
“No pharmas want to miss out on the next complementary checkpoint inhibitor partner,” said Arthur Kuan, CEO of Cold Genesys Inc.
Pharma and VC investment in oncolytic viruses has trended up over the last ten years from less than $2 million in 2010 to over $100 million in 2015 and $50-$100 million each year since.
Over the past three years, at least nine pharmas have acquired or partnered with oncolytic virus companies (see Table: “Pharma’s Oncolytic Virus Deals”).
“Checkpoint inhibitors saved oncolytic viruses.”
Oncolytic viruses were initially thought to work by preferentially targeting and replicating in cancer cells, then killing them through lysis. The field has since learned that a second mechanism may be equally if not more relevant -- when an oncolytic virus infects a tumor cell, it marks it for immune destruction.
After the cell dies, its tumor antigens are released and detected by T cells, leading to a powerful innate and adaptive immune response (see “Infectious Enthusiasm”).
“In the last 24-36 months, we realized that the viruses weren’t really causing a lot of lysis. They were causing a lot of immunological activity. We don’t think of it as a virus, but as a delivery