One Cancer-Killing Virus – The newest FDA-approved treatment for skin cancer doesn’t seem a real game changer. A $65,000 course of treatment extends melanoma patients’ lives by less than four and a half months, on average—and that result is barely statistically significant.
It’s how the new drug—Imlygic, made by the biotechnology company Amgen—works that has the oncology world so worked up. Imlygic is a virus—alive and infectious, the first to get a stamp of approval in the US for its ability to attack cancer cells. It opens a whole new front in the fight against cancer, which has the sneaky habit of coming back after chemotherapy, radiation, or surgery. “It is a totally new class of weapons that we can now use,” says Antonio Chiocca, a neurosurgeon at Brigham and Women’s Hospital. And the armory could be bigger, because coming up right behind Imlygic are over a dozen clinical trials for more anti-cancer viruses.
The idea of deploying viruses against cancer actually stretches back decades. The theory makes sense: When normal cells turn cancerous, replicating out of control, their virus-fighting machinery shuts down. That makes them vulnerable. But the field is littered with oncolytic viruses (“onco” is for cancer and “lytic” is lysis, or bursting) that fizzled out in clinical trials. “What this really is, in the end, is proof of concept,” says John Bell, a cancer researcher at the Ottawa Hospital Research Institute, who helped pioneer the use of these viruses. Not just proof of concept that a virus can fight cancer—but that all the extra problems with injecting a live virus are surmountable.
Imlygic itself is a reengineered version of the herpesvirus—the one that causes cold sores. To administer the drug, oncologists inject a massive dose—millions of viruses—directly into the skin tumor. Herpesvirus also prefers to infect cancer cells, busting them into bits. “The immune system sees all the debris,” says Chiocca. “This makes the immune system wake up and say, ‘Hey, there’s something going on here. Let’s check it out.’” So it’s a two-fer: Notionally, Imlygic attacks the tumor directly, and helps stimulate the patient’s own immune system into joining the fight.
The key was learning to engineer the virus into something useful. Researchers had to keep it from infecting healthy cells or causing cold sores, but make sure that it’d get pieces of viral and tumor protein to break up properly to alert the immune system (and express a new protein that also boosts the signal to the immune system). It wasn’t easy.
Although scientists know about the workings of the virus, they’re still pretty fuzzy on the role of the immune system here. Yes, the virus kills some of the cancer cells directly. But when the immune system sweeps in, is it just killing virus-infected cancer cells, or is it able to recognize any cancer cells, no matter where they are in the body? Howard Kaufman, a Rutgers Cancer Institute of New Jersey oncologist who is involved in Imlygic’s clinical trials, calls it one of the open questions for the field, which still “suffers from an acute lack of understanding the science behind it.” Some preliminary evidence suggests the virus is actually targeting all cancer cells, but the results are not clear yet.
What the data do show, though, is that Imlygic isn’t that great a drug by itself. In trials it extended survival time by 4.4 months and shrunk tumors for at least six months in 16 percent of patients. That’s not terribly effective (though its side effects—flu-like symptoms—are downright mild compared to most chemotherapy). It does show promise in combination with other drugs called checkpoint inhibitors, which inhibit the molecules that inhibit—so basically, stimulate—the immune system. One small trial of 19 patients with Imlygic and a checkpoint inhibitor called Yervoy found a response for half of the patients. “I think these combination approaches are where the real action is going to happen the future,” Bell says.
But as Bell also said, Imlygic’s real significance is as proof-of-concept. Oncolytic viruses work—now they have to get better at attacking cancer cells and in other types of cancer. Bell is working with vaccinia, a virus related to smallpox. Duke researchers are experimenting with a poliovirus. The company Oncolytics Biotech has a reovirus in clinical trials. Dozens more studies are underway. Imlygic is just generation one.