LIFE

Altered herpes virus used to fight melanoma

Laura Ungar
@laura_ungar

Shari Wells vividly recalls sitting with doctors at the University of Louisville's James Graham Brown Cancer Center and learning that her melanoma was so dangerous and advanced that she likely had less than six months to live.

But then came a clinical trial that she calls "my lifesaver," in which a modified version of the herpes virus is used to fight the deadliest form of skin cancer, which strikes 70,000 Americans a year, kills 9,000, and is on the rise.

The treatment "saved my life," said Wells, 56, of Ashland, Ky., whose cancer went into remission. "I was never so thankful in my whole life than for that medicine. Without it, I would be dead."

Herpes, known for cold sores and misery, is being made into a weapon, the latest example of turning one bane of humanity against another by using viruses to target cancer.

A study involving 436 late-stage melanoma patients at 64 centers around the globe, published in the current issue of the Journal of Clinical Oncology, shows that those injected with a genetically-modified version of the herpes simplex virus known as T-VEC responded better than a control group. Sixteen percent saw a significant decrease in tumor sizes within the first year of treatment that lasted for at least six months, compared with 2 percent of patients who didn't get T-VEC.

Researchers expect the treatment to yield even better results when combined with another type of immunotherapy, which uses the body's own immune system to fight cancer.

"It appears for many patients that (T-VEC) gives long-term remission and in some cases, cure," said Rob Coffin, who invented the treatment. "Quite a number of people in that study got a complete response; all their disease went away… I'm a great believer in the concept of using viruses to treat cancer."

Over the years, scientists have explored altering various viruses, including measles and polio, to combat several types of cancer, including brain tumors, breast cancers and others. A 2013 review in the journal Molecular Cancer concluded that cancer-fighting viruses armed with genes that stimulate the immune system, "are potent therapeutic cancer vaccines." Such viruses, including T-VEC, will be discussed at the annual meeting of the American Society of Clinical Oncology, which runs through June 2.

T-VEC, a product of California-based biotechnology company Amgen, is made by removing the gene that causes herpes from the virus and inserting a different gene that revs up the immune system, said researcher Jason Chesney of the University of Louisville, deputy director of the Brown Cancer Center and a co-author on the study. The virus enters cancer cells and "blows them up," he said, at the same time stimulating the body to fight the cancer.

In the study, patients were injected with viruses once every two weeks. Those with "durable," or lasting, responses saw at least a 50 percent decrease in the size of tumors that were injected and those that weren't. The most common side effects included things like fatigue, chills and nausea.

Wells, whose cancer first appeared in a mole on her left leg, was diagnosed with melanoma in 2007. Seven months later, she said, tests showed it had metastasized and was at Stage 4. She endured numerous procedures, including surgeries, but the cancer raged on — until she was accepted into the T-VEC trial beginning in 2010 and received two-and-a-half years of treatment.

"I was the first one accepted (in Louisville) and the first one in remission," she said.

Researchers and Amgen have high hopes for T-VEC. Amgen acquired the company Coffin founded, Massachusetts-based BioVex, in a billion-dollar deal in 2011. Examining early results of this Phase 3 sponsored study, an independent advisory panel to the U.S. Food and Drug Administration recommended T-VEC be approved, and researchers expect word within months from the agency.

FDA staff had initially expressed concerns about T-VEC, saying, among other things, that it was unclear from the study whether the treatment offered improved overall survival benefits to patients. Median overall survival differed by 4.4 months between T-VEC and the control group, the study says.

Researchers and melanoma experts say the best hope for patients may be combining T-VEC with another type of treatment called immune checkpoint inhibitors, which Chesney says "release the brakes in the immune system." He's currently testing this combined therapy at Brown Cancer Center.

Richard Daugherty, a 52-year-old patient of Chesney's from Jeffersonville, Ind., is undergoing this therapy for internal melanoma centered inside his groin and pelvis. When he was diagnosed in March, another doctor gave him up to a year to live. But one treatment with T-VEC reduced the size of tumors where it was injected by about 20 percent — and the only side effect he felt was fatigue.

Upon hearing the results before his second injection this week, "I thought I was imagining things," he said. "The excitement and hope is amazing. I completely feel like I'll go into …remission."

Timothy Turnham, executive director of the Washington, D.C-based Melanoma Research Foundation, agrees that combination therapy seems to be the best approach. He said the results of T-VEC alone were "interesting but not amazing," but when used with immune checkpoint inhibitors "the numbers you get are much stronger," and this combined treatment may prove to be a game-changer for melanoma treatment, especially given the relatively mild side effects.

Melanoma patient Mary Kenna Deddens, 66, is currently being injected with T-VEC as part of another study at the Brown Cancer Center and said she hopes the FDA approves it for wide use, because patients with advanced melanoma need more options.

"It would help a lot of people," she says. "It's another tool in the toolbox."

Reporter Laura Ungar, who also covers public health for USA Today, can be reached at (502)582-7190 or on Twitter @laura_ungar.