On October 27, the FDA approved the first oncolytic virus for the treatment of advanced melanoma in patients with inoperable tumors. Talimogene laherparepvec (T-VEC) was first developed by BioVex from the herpes simplex virus 1 (HSV-1). The technology was then acquired by Amgen in 2011, which now commercializes it under the name of Imlygic. Since the drug currently costs US$65,000 per treatment and extends patient’s lives for only 4.4 months, it does not seem like a significant improvement on the field of oncology. Yet this drug is being hailed as a game changer for its highly innovative way to fight cancer, a field which until now relied only on surgery, radiotherapy, chemotherapy, and immunotherapy. More drugs of this type are currently under development and expected to eventually make much larger developments on the field.
The oncolytic (from “onco” meaning cancer and “lytic” meaning breaking) properties of viruses are not a new discovery. More than 100 years ago, scientists observed that cancer patients had a short period of remission after contracting a viral disease. Researchers discovered that contracting influenza led leukemia patients to a short period of remission even though the cancer did not disappear for any of them. Sadly, in those cases remission typically lasted only for a few months. Yet further studies of this kind during the past century allowed to determine that, under correct circumstances, some viral infections were able to destroy tumors. It was later discovered that this effect is caused in part by the diminished ability of cancerous cells to fight viruses, thus viruses infect and replicate much faster in cancerous cells than in healthy ones.
Today, it has been determined that viruses can have three different cancer fighting mechanisms. The first occurs through direct oncolysis (rupture of the cell) of tumor cells through necrosis (cell death caused by external factors), apoptosis (programed cell death), and pyroptosis (programmed cell death after an immune response). The second is through the induction of apoptosis and necrotic death of neighboring uninfected cells by anti-angiogenesis and anti-vasculature, which means that the viruses limit the cell’s ability to generate blood vessels with which support itself. Finally, by cytotoxicity to cancer cells which helps to put micrometastases into a dormant state and to eliminate uninfected cancer cells.
HSV viruses are often preferred to fight cancer as they are among the fastest to reproduce, relatively easy to modify, mostly harmless to humans, and can be treated with antivirals. These viruses also have side effects much milder than conventional chemotherapy, usually flu-like symptoms. Imlygic or T-VEC was developed from HSV-1 and modified to secrete cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) in order to enhance the body’s anti-tumor immune response. The virus was also modified to avoid the development of herpes and to increase its selectivity to avoid the infection of non-tumor cells. Even if the T-VEC enters a healthy cell, it cannot replicate inside the cell. On the other hand, if it enters a cancerous cell it releases GM-CSF destroying the cell and allowing the immune system to target nearby cancerous cells.
Imlygic is currently being used for the treatment of inoperable-melanoma lesions through a direct injection into the affected area where it quickly replicates and destroys cancer cells. This drug is only the first of a new wave of cancer treatments which can bring hope to many patients suffering this deadly disease.
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