US FDA approves first ever oncolytic therapy for treating Melanoma, a type of skin cancer

Dr. Andrejs Liepins/SPL Killer T cells (orange) are recruited to attack malignant cells (mauve) in the viral-based cancer therapy T-VEC.

Dr. Andrejs Liepins/SPL
Killer T cells (orange) are recruited to attack malignant cells (mauve) in the viral-based cancer therapy T-VEC.

The first ever oncolytic virus therapy i.e. using viruses to preferentially kill cancer cells has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of melanoma lesions in the skin and lymph nodes. Melanoma is a type of skin cancer, that accounts for most of the skin cancer-related deaths, and is most often caused by exposure to ultraviolet (UV) light. According to the National Cancer Institute approximately 74,000 Americans will be diagnosed with melanoma and nearly 10,000 will die from the disease in 2015.

“Melanoma is a serious disease that can advance and spread to other parts of the body, where it becomes difficult to treat. This approval provides patients and health care providers with a novel treatment for melanoma,” said Karen Midthun, M.D., director of the FDA’s Center for Biologics Evaluation and Research.

How does it work?

The FDA-approved Imlygic (talimogene laherparepvec or T-VEC) is a genetically engineered virus that is used to treat advanced melanoma, especially lesions that cannot be removed completely by surgery. They are injected directly into the lesions, where it replicates inside the cancer cells and causes the cells to rupture and die.

A typical course with Imlygic involves as a series of injections into the melanoma lesions. After the first injection, a second dose is administered three weeks later, followed by additional doses every two weeks for at least six months, unless other treatment is required or until there are no remaining injectable lesions to treat.

Imlygic is actually a modified, live oncolytic herpes virus therapy, so it mean herpes virus infection can also occur. Hence it should not be given to individuals with suppressed immune systems or who are pregnant. However, researchers have tried to alter T-VEC drastically to reduce its ability to cause herpes. Researchers also inserted a gene that could produce a protein that stimulates the immune system, which makes the virus even more potent against cancer.

But does it work or extend longevity?

The efficacy and safety were assessed in a multi-center study involving 436 participants with metastatic melanoma (the cancer had spread to distant parts of the body from its primary lesion) and could not be surgically removed. The melanoma in the skin and lymph nodes of patients were treated with Imlygic and a comparator therapy for atleast 6months or until there were no remaining injectable lesions.

16.3% of the participants in the clinical trial who received Imlygic experienced a decrease in their skin and lymph node lesions, lasting for a minimum of six months, compared to 2.1% of the participants receiving the comparator therapy. Some of the common side effects observed in the participants of the clinical study were fatigue, chills, fever, nausea, flu-like symptoms and pain at the injection site.

The virus shrank tumours in people with advanced melanoma and extended patient survival by a median of 4.4 months. However, it did not have an effect on melanoma that spread to the brain, bone, liver, lungs, or other internal organs.

Is it a novel treatment?

Surprisingly, no! As early as 1800s, physicians started noting that cancer patients sometimes went into remission after experiencing a viral infection. This led to an era, where clinicians injected a wide range of viruses into cancer patients- some that led to the destruction of the tumor and some that proved fatal to the patient!

For some reason, viruses preferentially infect cancer cells.  Researchers saw that two situations can cause the body to have sub-optimal antiviral response 1) Malignancy or spread of cancer cells can suppress antiviral response and 2) Mutated cancer cells are more prone to infection. This makes cancerous cells more susceptible to virus infections and hence was particularly attractive in developing oncolytic therapies.

However, unlike the wild viruses used in those mid-twentieth-century experiments, some of today’s anti-cancer viruses are engineered with utmost caution. Even in the case of T-VEC, researchers are continuing to look for ways to improve it, especially the delivery method. If it could be delivered directly into the blood stream or systemically, the virus could target these tumors better- even in organs that are difficult to reach with an injection.

This would require a technique to prevent the body from mounting an immune response to the virus prematurely, which would disable it before it could reach and kill tumour cells, says Howard Kaufman, a cancer researcher at Rutgers Cancer Institute of New Jersey.

Stephen Hodi, an oncologist at the Dana-Farber Cancer Institute in Boston, Massachusetts notes, “Administering T-VEC in combination with cancer immunotherapy could prove particularly effective.” In June 2014, a small clinical trial by Amgen suggested that this combination may boost effectiveness over that of the immunotherapies alone.

If these cancer-killing viruses could be directly targeted to the organ of choice through bloodstream rather than injecting it to an organ, it will open up a method to treat a wide range of cancers.

“The era of the oncolytic virus is probably here,” says Stephen Russell, a cancer researcher and haematologist at the Mayo Clinic in Rochester, Minnesota. “I expect to see a great deal happening over the next few years.”

Imlygic is manufactured by BioVex Inc., a subsidiary of Amgen Inc., based in Thousand Oaks, California.

Source: FDA, Nature News

Original paper of the clinical trial

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