Scientists successfully use herpes virus to treat skin cancer

By Stephen Beech

The deadliest form of skin cancer can be treated using the herpes virus, suggests a new study.

Scientists found that a genetically engineered herpes simplex virus, when combined with immunotherapy, reduced or eliminated tumors in one-third of melanoma patients during clinical trials.

The herpes simplex virus type 1 (HSV-1), which affects almost two-thirds of the world’s population and is generally associated with oral herpes, may cause painful cold sores or fever blisters around the mouth.

But, when genetically engineered to fight cancer, scientists say the virus may also play an important role in treating advanced melanoma, skin cancer that has spread to other parts of the body.

The study involved 140 patients who had advanced melanoma that did not respond or stopped responding to immunotherapy, which uses the body’s own immune system to fight cancer.

They were treated with a genetically modified HSV-1 in combination with an immunotherapy called nivolumab.

The findings, published in the Journal of Clinical Oncology, showed that, by the end of the clinical trial, one-third of the participants had their tumors shrunk by at least 30%, and nearly one out of six patients had tumors completely disappear.

Principal investigator Dr. Gino In said: “These findings are very encouraging because melanoma is the fifth most common cancer for adults, and about half of all advanced melanoma cases cannot be managed with currently available immunotherapy treatments.

“The survival rate of untreatable advanced melanoma is only a few years, so this new therapy offers hope to patients who may have run out of options to fight the cancer.”

He said the genetically modified HSV-1 evaluated in the study, RP1, is one of a relatively new, innovative class of cancer immunotherapy drugs known as oncolytic viruses that are designed to target and destroy cancer tumors while generating an anti-tumor immune response throughout the entire body.

In January 2025, the U.S. Food and Drug Administration granted priority review to RP1 with nivolumab for patients with advanced melanoma whose cancer had not responded to prior immunotherapy.

When injected into a tumor, RP1 replicates, killing off the cancer cells while leaving healthy cells unharmed.

RP1 also stimulates the body’s white blood cells to seek out and destroy any other cancer cells in the body.

The second cancer drug used in the study, nivolumab, is a standard immunotherapy treatment in fighting advanced melanoma and other cancers that have spread through the body.

Researchers believed that nivolumab, which works by using the body’s own immune system to fight and destroy cancer cells, would enhance the potential effect of RP1.

Patients who took part in the study had already been treated with minimal success by one or more immunotherapy therapies and had to have more than one tumor that could be injected with RP1.

Some tumors were considered “superficial” - meaning visible on the skin, or just below the skin’s surface - and some were located deeper in the body, including in the liver or lungs.

Researchers injected both superficial and deep tumors with RP1, which does not cause herpes.

During the trial, patients were given a combined therapy of RP1 and nivolumab every two weeks for up to eight cycles.

If patients responded to the treatment, they continued on nivolumab alone every four weeks for up to 30 cycles over two years.

The research team measured both treated and untreated tumors.

They discovered that not only did injected tumor size shrink in a third of the patients by 30%, but that patients’ uninjected tumors also shrank or even disappeared, just as frequently and as deeply.

Dr. In said, “This result suggests that RPI is effective in targeting cancer throughout the entire body and not just the injected tumor, which expands the potential effectiveness of the drug because some tumors may be more difficult or impossible to reach."

The study also found that RP1 was well-tolerated and had a "favorable" safety outcome.

While it is too soon to tell if the positive outcomes remain permanent, the research team is "optimistic" about the future of RP1 therapy.

Dr. In, from the University of Southern California's Keck School of Medicine, added: "I believe that oncolytic viruses will open up an important new approach to fighting cancer in some patients in the near future."

Dr. In and his colleagues have now launched a phase 3 trial, known as IGNYTE-3, to confirm their findings in a global group of more than 400 participants.