Genetically Modified Cold Sore Virus Shows Promise in Melanoma

A new immunotherapy known as talimogene laherparepvec (T-VEC), or Ovcovex GM-CSF, has shown the ability to shrink advanced melanoma tumors. T-VEC is a genetically modified version of herpes simplex virus type 1, the virus that causes cold sores. T-VEC was also engineered to produce GM-CSF (granulocyte-macrophage colony-stimulating factor), a protein that stimulates the immune system.  Amgen, the California-based biopharmaceutical company that is developing the experimental cancer therapy, announced on March 19 that T-VEC had shown positive results in an advanced melanoma clinical trial.

All 439 patients treated in the phase III trial had advanced, unresected stage III or IV melanoma. The patients were randomized to receive either the new immunotherapy or GM-CSF protein alone. For those in the GM-CSF group, the protein was injected under the skin to boost the immune system. The other patients received injections of T-VEC directly into their tumors every 2 weeks.

The new results, according to Amgen, showed that 16% of patients treated with T-VEC had either complete or partial tumor shrinkage compared to 2% of patients treated with GM-CSF alone. The difference was statistically significant and not simply due to chance. Called a durable response rate (DRR), this difference in tumor response was continuous and lasted for at least 6 months.

The company also announced that the new therapy may be prolonging the life of some patients. However, the study is still ongoing and more data is needed to determine whether this trend is in fact statistically significant or is simply due to chance. The full trial results, including overall survival, will not be available until the trial is complete. The results will likely be announced later this year, according to Amgen.


So far, the most common side effects experienced by patients in trial have been fatigue, chills, and pyrexia, or high fever. Serious adverse events have included cellulitis (a bacterial skin infection), pyrexia, and melanoma progression.

T-VEC is designed to work both locally, within the injected tumor, and systemically to boost a patient’s antitumor immune response. The virus specifically targets tumor cells. Once inside a tumor cell, the virus multiplies itself repeatedly until the cell membrane ruptures, an event called lysis. Lysis releases many copies of the virus into the surrounding tumor tissue. In addition to its own tumor-attacking ability, the virus has been engineered to make GM-CSF protein, which activates the immune system to better attack tumors.

“[There is the] possible generation of a local immune response that could also stimulate systemic immunity, leading to regression of distant uninjected metastases with this therapy,” says Jeffrey Weber, MD, PhD, melanoma clinician and researcher at the Moffitt Cancer Center in Tampa, Florida.

According to Weber, only a small cohort of melanoma patients would be eligible for treatment with T-VEC, if it is approved. This group includes patients with smaller tumors who are not eligible for (or have failed) localized treatment, such as limb perfusion—a drug-delivery technique used for tumors that are confined to a limb. Older patients who cannot tolerate more toxic therapies could benefit as well.

Weber sees T-VEC being used for those with loco-regional disease, but not for the majority of advanced stage IV unresectable patients. For the final phase III data results, “I would want to see survival data and true progression-free survival data in patients that had a significant burden of distant disease,” he says.