Giving the immune system a gentle nudge and pointing it in the right direction is a simplified way to describe the complexities surrounding cancer immunotherapy. In the past several years with new discoveries and approval of several key immunotherapeutic compounds, the field has attracted a huge amount of attention.

Over the years researchers have attempted to modulate the human immune system in several ways, for example through the use of cytokines to stimulate immune cell activity; monoclonal antibodies that target cancer cells and act as a beacon for immune cells to home in on; and cancer vaccines, which prime the immune system toward oncogenic antigens that would not typically be present on the surface of normal cells. Several years ago researchers developed a new approach that they believed would be more effective than other cancer immunotherapies since it would deliver a veritable one-two punch to the tumor it was targeting—they termed it viral oncolytic therapy.

This approach utilized a genetically modified virus that would preferentially infect and kill cancer cells. The first way in which the virus would destroy the cancer is through lysis of the cell as it fills up with newly synthesized viral particles to the point of rupture. The release of new infectious viral particles helps to destroy remaining tumor cells. The second-way oncolytic therapy helps to control cancer growth is through the indirect stimulation of antitumor immune response. The lytic destruction of the cancer cells releases an array of cancer antigens that are often immunogenic. Many researchers have taken advantage of genetic engineering tools and inserted cytokine genes that will be secreted by the cancer cell while it is in the process of creating the viral particles.

Clinical trials using viral oncotherapy started several years ago using an engineered herpes simplex-1 virus that contains the human cytokine gene for granulocyte-macrophage colony stimulating factor (GM-CSF) to enhance host innate immune response toward the cancerous cells.

Now, the FDA has approved Amgen’s Imlygic (talimogene laherparepvec or T-VEC) as the first oncolytic viral therapy for the local treatment of unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma that is recurrent after the initial surgery.

“Advanced melanoma remains a complex disease to treat, requiring the use of several modalities over the course of a patient's therapeutic journey,” explained Howard L. Kaufman, M.D., associate director for Clinical Science at the Rutgers Cancer Institute of New Jersey and principal investigator for the clinical trial that helped pave the way for FDA approval. “As an oncolytic viral therapy, Imlygic has a unique approach, and provides another option for treating eligible patients with unresectable disease that have recurred after initial surgery.”

The clinical trial results did not show that Imlygic was able to improve overall survival or have an effect on visceral metastases, however of the treated patients that achieved a durable response almost 30% had complete remission and 70% had a durable partial remission.

“Not all melanoma patients currently benefit from available therapies, and Imlygic represents an important new option that can provide meaningful, durable responses for patients with this aggressive and complex disease,” noted Sean E. Harper, M.D., executive vice president of research and development at Amgen. “Immunotherapy is an exciting area for cancer research, and we are currently studying Imlygic in combination with other immunotherapies in advanced melanoma and other solid tumors.” 

While Amgen expects the compound to be available to patients almost immediately, it won’t come cheap as the estimated average cost of treatment will run around $65,000. Yet, for many patients who have run the gamut of treatment options, the current price point will be of little consequence.

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