In 2015, the US Food and Drug Administration (FDA) approved the first oncolytic viral therapy in the United States, talimogene laherparepvec.1 The therapy, often called TVEC, is a genetically modified herpes simplex 1 virus used as a local treatment for unresectable cutaneous, subcutaneous, and nodal lesions in patients with melanoma recurrent after initial surgery.

Oncolytic viruses are typically modified from an existing virus, such as the herpes simplex or the polio virus, that infects and breaks down cancer cells without harming normal tissue.2 A variety of viruses are being researched in cancers including melanoma, brain tumors, breast cancers, and others.

“We are in the middle of two revolutions for immunotherapy for solid tumors,” said Juan Fueyo, MD, professor of neuro-oncology at The University of Texas MD Anderson Cancer Center in Houston. “The first is with the use of immune checkpoint inhibitors and the second is with oncolytic viruses.”

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Two-Pronged Attack

Although the exact mechanism of action of TVEC is unknown, the oncolytic virus is thought to cause cell death, which ruptures tumors, releasing tumor-derived antigens that, along with granulocyte macrophage colony stimulating factor (GM-CSF), may promote an anti-tumor immune response.

To understand the history of oncolytic viruses, you have to go back “many years,” Dr Fueyo said. Over the years, there were reports that patients with cancer sometimes had improvements in their disease after getting viral infections. For example, a case study detailed how a child with Burkett lymphoma who contracted measles later saw an improvement in his cancer.

When these therapies were first being studied, investigators were using viruses deficient for replication as vectors, Dr Fueyo explained. This meant that researchers had to develop viruses that were replication-competent, and would behave like a virus only within tumor cells.

Today, research into oncolytic viruses is most advanced in the area of melanoma, with the recent approval of TVEC. TVEC was approved based on data from OPTiM, a phase 3 clinical trial that randomly assigned 436 patients 2:1 to receive TVAC plus GM-CSF or GM-CSF alone.3 Patients assigned to the experimental arm had a significantly higher durable response rate (16.3% vs 2.1%; P < .001) and overall response rate (26.4% vs 5.7%) compared with GM-CSF alone. Common adverse events with TVEC were fatigue, chills, and pyrexia.