Pharmaceutical giant Johnson & Johnson announced on 2 May that it would pay up to US$1 billion to acquire a company that makes cancer-killing viruses. It was a striking show of support for a still-unproven treatment, but the bid is just the latest sign that industry and academics are warming to the approach.
In February, Merck, headquartered in Kenilworth, New Jersey, agreed to pay US$394 million to snatch up an Australian firm working on cancer-killing, or ‘oncolytic’, viruses. And in April, about 300 people showed up for the oversubscribed International Oncolytic Virus Conference in Oxford, UK. When the conference launched in the early 2000s, there were only about 60 attendees. “They were very small meetings for these crazy people working with viruses,” says Jean-Simon Diallo, a molecular biologist at the Ottawa Hospital Research Institute. “We’ve really seen a shift.”
Diallo credits a confluence of developments with igniting the field. One was a 2015 US Food and Drug Administration (FDA) decision to approve a modified herpes virus called talimogene laherparepvec (Imlygic) to treat some forms of melanoma. It was the first cancer-fighting virus to win regulatory support in the lucrative US market. Another is emerging evidence — largely from animal studies — that the viruses might work better when given in concert with other therapies called checkpoint inhibitors, which boost immune responses against tumours.
“The intersection of these two events has really put some spice in the oncolytic-virus field,” says Diallo. “The checkpoint inhibitors have really turned things around for everybody.”
Death by association
Researchers have been trying to develop cancer-fighting viruses for decades, hoping to capitalize on centuries-old observations that people with cancer sometimes go into remission after contracting a viral infection. That has spurred teams to develop a panoply of viruses — some engineered to make them safer or more effective against cancer — that have passed through the gauntlet of a clinical trial.
Many of these trials have met with little success. Even Imlygic fell short of showing a statistically significant improvement in patient survival during a pivotal clinical trial1. Still, the results were enough to persuade the FDA to approve the therapy for melanomas that had resisted other treatments. That study also sparked some hope among researchers by showing that a virus injected directly into one tumour could rein in tumours elsewhere in the body.
It does so by generating an immune response. After the virus infects and kills cancer cells, the immune system kicks in to eliminate the virus, and winds up also getting rid of the dead cancer cells. “The side effect from eliminating the virus is that the systemic immune system recognizes the cancer cells,” says Tomoki Todo, a neurosurgeon at the University of Tokyo. “Then it starts to attack even those cancer cells that are not infected by the virus.”
Scientists reasoned that bolstering such an immune response — for example, by using a checkpoint inhibitor — could amplify this indirect effect. Around the time of Imlygic’s approval, checkpoint inhibitors were showing promise against several different cancers, including melanoma and lung cancer. These inhibitors sometimes send cancer into remission for years, but only for a fraction of people.
Studies in mice suggest that combining checkpoint inhibitors with cancer-killing viruses might boost that percentage. And in a small clinical trial involving 21 people with advanced melanoma, Imlygic, together with a checkpoint inhibitor called pembrolizumab, significantly shrank tumours in 62% of participants and wiped them out altogether in 33% of cases2.
When researchers have combined checkpoint inhibitors with other treatments, they have met with mixed success. Some fervently anticipated combinations have failed in clinical trials. “Could the same thing happen with oncolytic viruses? Sure,” says Dmitriy Zamarin, an oncologist at the Memorial Sloan Kettering Cancer Center in New York City.
But Zamarin and others are cautiously optimistic. Many checkpoint-inhibitor combinations target a specific protein, Zamarin notes, whereas oncolytic viruses provoke a much broader immune response that can target cancer in a number of different ways. “That gives us some comfort,” he says.
Nature 557, 150-151 (2018)