Virotherapy: skin cancer successfully treated with herpes-based drug

May 27, 2015 | HANNAH DEVLIN, The guardian

Virotherapy’ uses modified herpes virus to attack melanoma cells and has potential to overcome cancer even when disease has spread throughout the body
Patients with aggressive skin cancer have been treated successfully using a drug based on the herpes virus, in a trial that could pave the way for a new generation of cancer treatments.
The findings mark the first positive phase 3 trial results for cancer “virotherapy”, where one disease is harnessed and used to attack another. If approved, the drug, called T-VEC, could be more widely available for cancer patients by next year, scientists predicted.
Crucially, the therapy has the potential to overcome cancer even when the disease has spread to organs throughout the body, offering hope in future to patients who have been faced with the bleakest prognosis.
Kevin Harrington, professor of biological cancer therapies at the Institute of Cancer Research London, who led the work, said: “This is the big promise of this treatment. It’s the first time a virotherapy has been shown to be successful in a phase 3 trial.”
In the trial, involving more than 400 patients with aggressive melanoma, one in four patients responded to the treatment, and 16% were still in remission after six months. About 10% of the patients treated had “complete remission”, with no detectable cancer remaining - considered a cure if the patient is still cancer-free five years after diagnosis.
The results are especially encouraging, Harrington said, because all the patients had inoperable, relapsed or metastatic melanoma with no conventional treatment options available to them. “They had disease that ranged from dozens to hundreds of deposits of melanoma on a limb all the way to patients where cancer had spread to the lungs and liver,” he said.
The treatment works by mounting a two-pronged attack on cancer. It is based on a genetically “neutered” version of the herpes virus, which has been modified to stop it producing the protein that allows it to infect healthy cells. Cancer cells then produce their own version of the blocked protein, filling in the deficit and allowing the modified virus to thrive within cancerous tissue.
The herpes multiplies vigorously inside the cancer cells until they burst open, spilling the virus into the surrounding area, triggering a secondary immune reaction against the tumour.
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, said: “We may normally think of viruses as the enemies of mankind, but it’s their very ability to specifically infect and kill human cells that can make them such promising cancer treatments. In this case we are harnessing the ability of an engineered virus to kill cancer cells and stimulate an immune response.”
Once the immune system has been nudged into action by the T-VEC treatment, it appears to develop an enhanced ability to detect and attack cancer throughout the body. Scientists are not sure why this happens, but the latest trial confirmed the effect, showing that even secondary tumours that had not been infected by the virus shrank or disappeared.
“It’s like an unmasking of the cancer,” said Harrington. “The patient’s immune system wakes up and attacks the cancer cells wherever they are in the body.”
The therapy is given by injection and in the trial patients received a dose every two weeks for up to 18 months. The side-effects tend to be far milder than chemotherapy drugs, with patients typically experiencing mild flu-like symptoms after the first few injections.
Dr Hayley Frend, science information manager at Cancer Research UK, said: “Using a virus to both kill cancer cells and nudge the immune system into attacking them is exciting. Previous studies have shown T-VEC could benefit some people with advanced skin cancer, but this is the first study to prove an increase in survival.”
Patients with stage III and early stage IV melanoma treated with T-VEC (163 people in total) lived an average of 41 months, the trial found. This compared with an average survival of 21.5 months in the 66 earlier-stage patients who received the control treatment.
Rather than the traditional clinical trial, where a drug is compared to a placebo, the control group were given a protein designed to stimulate the immune response against cancer, but without the virus component of the treatment.
The drug, developed by the company Amgen, has been submitted to both the FDA and the European Medicines Agency, and could be available to US patients by next year if approved, and in Europe soon afterwards. Similar treatments are also being trialled for head and neck cancers
More than 13,000 people are diagnosed with malignant melanoma skin cancer each year in the UK, and about 88% of patients survive for more than five years. However, the survival rates for aggressive forms of skin cancer and when the cancer has spread to other organs are far worse.
The possibility that viruses could be harnessed to tackle cancer was first raised in the early twentieth century, when doctors noted that cancer patients who caught measles, hepatitis or glandular fever occasionally underwent a temporary recovery. During an early trial in 1949, patients with Hodgkin’s lymphoma were injected with viral hepatitis. One patient died and 13 contracted hepatitis, but seven experienced temporary remission.
Genetic engineering, which has allowed scientists to create safe versions of natural viruses has led to a revival of the concept, and trials of virotherapies based on infections including herpes, measles and vaccinia (which was used in the smallpox vaccine) are currently underway.
The findings are published today in the Journal of Clinical Oncology  .