Oncolytic Viruses Make Their Debut
Does a virus engineered to harness the immune system to fight cancer sound like a clever idea? Amgen (Thousand Oaks, CA) certainly thinks so, because their talimogene laherparepvec (T-Vec) recently earned an FDA approval to fight inoperable melanoma recurrent after initial surgery. Oncolytic viruses—like T-Vec—have the attention of both industry media and mainstream news programs. This new class of therapy is an elegant “hack” of the immune system, so let’s explore the science behind the latest drug approval fighting cancer.
An Opportunistic Virus Is Made
T-Vec is an oncolytic virus—an engineered virus that infects and kills cancer cells. Oncolytic viruses are created in the lab by genetically modifying existing viruses in two ways:
- Making the virus safe by removing genes that allow the virus to spead disease.
- Engineering viral surface proteins, so the virus recognizes and binds to the cell receptors of cancerous cells, disregarding the healthy, non-cancerous cells.
The oncolytic virus follows the same life cycle as any virus—once inside the human body it hunts down, attaches to, and enters its host cell. In this case, the host happens to be cancer cells! The virally infected cancer cells are destroyed via the process of cell lysis—as the oncolytic virus multiplies inside of the cells, it causes the cancer cells to burst open and kills them. Spewing from the burst cells are new infectious particles that further target remaining tumor cells. The presence of a replicating virus also activates the patient’s immune response, so the cancerous area is further attacked.
The Vector of T-Vec
Interestingly enough, the virus used in T-Vec is a modified herpes simplex 1 virus. The key modifications made to ensure safety and efficacy are:
- Deletion of viral gene ICP34.5: This gene codes for a protein that enables the virus to replicate in human cells by blocking a human protein known as PKR. PKR prevents viral replication and is less active in most tumor cells. This makes the virus able to selectively replicate in tumor cells.
- Deletion of viral gene ICP47: This gene codes for a viral protein that inhibits the immune response to the virus by turning off a process called antigen presentation. Normally, one of the key ways the immune system “knows” to attack a virally-infected cell is by recognizing antigens—or fragments of viral proteins—displayed on the infected cell’s surface. Turning this process off helps the virus evade the immune system. Turning it back on prompts the immune system to attack virus-infected tumor cells.
- Activation of viral gene US11: This gene increases viral replication in tumor cells.
- Insertion of a gene for the human protein GM-CSF: This gene activates the immune system and aids in the overall immune response towards the tumor triggered by viral infection.
The Oncolytic Bandwagon
T-Vec is currently being studied for possible use in other solid tumors, and Amgen is collaborating with Merck (Kenilworth, NJ) and Roche (Basel, Switzerland) to test T-Vec in combination with their checkpoint inhibitor therapies. The potential of this treatment has also beckoned other companies to the oncolytic bandwagon:
Cocktail Fodder: Renegade Viruses Of The Past
The idea of using viruses to challenge cancer is cutting-edge, 21st-century science—but the inkling of a cancer-fighting virus was first observed more than a century ago. In 1904, an editorial published in the American Journal of Medical Science revealed a spontaneous regression of cervical cancer occurred after administration of a rabies vaccination. A few years later, a similar phenomenon occurred: the remission of lymphoma after a measles virus infection. Our modern understanding of viruses at the molecular level combined with our increased ability to manipulate genetic material made this century-old idea a medical reality of today.