For as long as humans have been aware of sexually transmitted diseases, herpes has played the role of villain. The incurable virus' sole purpose in modern life, it seems, has been to cause pain and discomfort and fear between the sheets. It might as well wear a sinister little mask and laugh a mwahaha cackle with each new victim it infects.
But its evil rap may soon change: Scientists are now using the herpes simplex virus to fight—and one day possibly cure—cancer. The little villain is turning on the big villain.
The technique is called virotherapy. What is it, exactly? "In general, it means using a virus to kill cancer cells," said Howard Kaufman, a professor of surgery at Rutgers University's Robert Wood Johnson Medical School and a researcher at the forefront of the treatment.
The basic premise works like this: "First, we think many viruses have a natural ability to kill tumor cells," Kaufman told Fusion. Second, and more importantly, injecting a patient with a virus triggers an immune response that is usually switched off when a patient has cancer.
While scientists have been playing with the technique for years, researchers have only recently begun to see its full potential, thanks to the advent of bioengineering. Yes, we’re now entering a virotherapy renaissance—and herpes is the hero.
As anyone who's ever gotten a cold knows, viruses have fantastic breaking-and-entering tactics. Every infection you get, from chickenpox to measles, starts off with a virus attaching itself to your cells. Once it’s glommed on, it injects its genetic code and uses the cell’s gene-making machinery to replicate itself over and over again. From there, it breaks free from the host cell, often destroying it in the process, and continues on its way infecting other cells.
During virotherapy, a modified virus such as herpes would gain entry into cancer cells—then destroy them. But here’s where things get interesting.
While our healthy cells have developed ways to fight off viruses, cancer cells have not. "Many normal cells have a complicated network of molecules to help protect against a virus," said Kaufman. "But turns out cancer cells are deficient in anti-viral factors." Which means cancer cells are pretty defenseless against viruses—something researchers hope to exploit.
As most oncologists will tell you, cancer can behave differently from patient to patient, which is why finding a cure-all treatment has been so difficult. However, one of cancer's most consistent traits is that it’s figured out how to stop a patient's immune system from attacking it. Once cancer spreads, your immune system has very little recourse to fight it. However, "Delivering a virus right where the tumor is growing seems to reverse that immune suppression," says Kaufman.
This reversal is key. If virotherapy can restart the patient's immune response, it could mean fighting cancer in late stages, when it has already spread—and help save lives.
New as the concept of virotherapy may be to the public, it isn't entirely new to researchers. At the end of the nineteenth century, doctors began noticing that when cancer patients contracted an unrelated virus, their cancer went into remission. Back then, however, these cases were rare, and there wasn't much doctors could do with the observation.
In the 1950s and 60s, virotherapy—also known as "oncolytic,” or cancer-busting, viruses—saw a resurgence and coordinated research efforts began. But doctors didn't have the technology at the time to manipulate the virus to do what they wanted. Not only did the virus itself present risks, but the body's natural immune response would attack the virus, preventing it from attacking the cancer.
Then came biotechnology, which allowed scientists to co-opt a virus’ natural urge to destroy cells and use it for good. Specifically, thanks to recombinant DNA technology—or the ability to manipulate genes—researchers can now modify viruses so they don't harm the patient.
Scientists all over the world are now exploring whether viruses can double as cancer-fighting warriors. The National Institutes of Health's website ClinicalTrials.gov, which tracks clinical trials, alone lists roughly 40 ongoing or completed studies testing virotherapy.
And this past spring, Kaufman and a team of researchers reported virotherapy’s first big success in a clinical trial. The team used modified herpes to treat advanced skin cancer in 436 patients. Roughly a quarter of the patients responded to the treatment—about 16 percent were still in remission six months later, and 10 percent saw a complete remission, which means no detectable cancer remained in their body at the time of publication. If that's still the case in five years, it's considered a cure.
The virotherapy drug, called T-VEC, could kill off cancer even after it had spread.
The success of that trial led an FDA panel to recommend that T-VEC be approved this past April. While the FDA, which oversees approval of new treatments, told Fusion that it couldn't comment on the drug's status, Kaufman said he's hopeful it will be approved as soon as August and available for use within a year. This would make T-VEC the first virotherapy drug available in the U.S. "We’re just beginning to talk about a cure," said Kaufman.
Meanwhile, halfway around the world, the future is already here. As scientists in the U.S. furiously work to gain FDA approval for virotherapy, in Latvia, a form of the treatment is already being put into practice.
The virotherapy drug called Rigvir has been available since 2008. The drug contains a non-modified virus used to treat melanoma and sarcomas, and it's had a decent success rate over the past four or so years, according to the country's International Virotherapy Center (IVC), which uses it as part of its virotherapy program.
"We already have cases of astounding cure of cancer for patients at stage III and stage IV in our practice with Rigvir," said Kaspars Losans, the medical director of the center. "Virotherapy, for sure, is the next step in cancer treatment."
Today, scientists are researching which viruses can be manipulated to work best in fighting cancer. "We've looked at a number of viruses" from smallpox and measles to Newcastle Disease and herpes-simplex—as well as viruses such as cow pox, which doesn't cause disease in humans but may still be able to kill cancer cells, said Kaufman.
The side effects? Unlike chemotherapy and radiation, which can put a patient through months of agony, virotherapy has been shown to cause mild and short-lived symptoms. "The patients we treated definitely had flu-like symptoms," said Loren Mell, a virotherapy researcher at University of California, San Diego, in reference to a recent phase I clinical trial in which he gave patients a modified vaccina virus in conjunction with chemotherapy and radiation to determine if such a treatment was safe. "But it was temporary."
Kaufman echoed that sentiment, saying he's seen virotherapy patients experience low-grade fever, chills, fatigue, and pain at injection site—but nothing nearly as excruciating as the symptoms associated with chemotherapy.
Of course, despite virotherapy's promise, researchers must still overcome several hurdles before it becomes the standard of care. While much has been written about Rigvir’s succes in Latvia, experts I spoke with in the U.S. didn't have much insight into its effectiveness. The FDA would not comment if it was ever submitted for use in the States. So whether the virotherapy works as promised still remains to be seen.
In the meantime, researchers are working to determine which patients will respond best to virotherapy since it's impossible to know from the outset.
"It's a very active area of research" said Siwan Hu-Lieskovan a clinical instructor at the UCLA Department of Medicine who specializes in hematology and oncology. And yet, "we unfortunately don't have a way of knowing who will respond and who won't."
Taryn Hillin is Fusion's love and sex writer, with a large focus on the science of relationships. She also loves dogs, Bourbon barrel-aged beers and popcorn — not necessarily in that order.