Viruses cause disease and death. In fact, we know of about 219 types of viruses that can make us sick or even kill us. But this number is insignificant compared to the thousands of different viruses that live in your gut, and the thousands that are used for applications in medicine, agriculture, nanotechnology, and research. One group of viruses, called oncolytic viruses (OVs), are even having a big impact in our fight against cancer. 

How do Oncolytic viruses work? 

OVs can kill cancer cells with a two-punch attack. The first punch is by directly infecting and killing cancer cells. The second is more indirect, but extremely important.  

As the cancer cell dies, it releases parts of itself, small cell fragments known as tumor antigens that are recognized by a group of immune cells called antigen presenting cells (APCs). APCs oversee the clearing out of dying, or defective cells and when they see tumor antigens, they sound the alarm to other immune cells. APCs secrete signaling molecules called cytokines to recruit more immune cells, activating an army of different cancer fighting cells known as lymphocytes. This activation of immune cells helps the immune system recognize and attack cancer cells anywhere in the body (metastatic lesions), including organs that are difficult to reach like the brain, the spleen, or the bone. 

What are the benefits of using OVs in cancer therapy? 

Unlike treatments like radiation and chemotherapy, OVs can be engineered to be highly specific for cancer cells while leaving healthy cells unharmed. OVs are naturally attracted to cancer cells because as cells become cancerous, they lose some of the antiviral defenses they had as healthy cells. This allows the virus to replicate (make copies of itself), killing the cancer cell in the process, and then spreading to nearby cancer cells. As the virus spreads, the cancer cells become more visible to the immune system, activating a targeted immune response against the cancer.  

How close are we to treating cancer with OVs? 

In 2015, the FDA approved the first oncolytic virus, T-VEC, for the treatment of late-stage inoperable skin melanomas. T-VEC is an OV derived from the Herpes Simplex Virus 1 that causes the common cold sore. Engineered to be safer, T-VEC replicates only in cancer cells and carries a gene that boosts the local immune response. T-VEC is being evaluated in combination with immune checkpoint inhibitors, a type of immunotherapy designed to activate the immune system by taking the brakes off from lymphocytes that became fatigued or unable to attack the tumor.  

There are more than 320 clinical trials at various stages of development to evaluate a wide range of viruses to treat liver, pancreatic, and other hard to treat cancers. Researchers are also “arming” viruses, by inserting instructions for the virus to express cytokines that further amplify anti-tumor immune responses. OVs can also prevent delivery of nutrients and oxygen to the tumor, which speeds up immune responses and tumor death. 

Challenges with OVs  

A major challenge for oncolytic virotherapy is preventing the patients immune system from eliminating the virus before it can reach the tumor. Injecting the OV directly into the tumor can help to prevent this, but it can more difficult if the tumor is located in organs that are hard to reach. Another approach could be to use the patients own immune cells as a “Trojan horse” to  deliver the OV to the tumor and avoid detection by the immune system. 

The future for OVs is promising and research in this field is encouraging. Recent clinical data suggests that OVs can be used on their own as an immunotherapy, in combination with current treatments, or even to enhance the effectiveness of other immunotherapies. There are more than 320 clinical trials evaluating OVs to treat different cancers. It is only a matter of time before they become part of personalized cancer treatments, offering customized medicine that focus on harnessing and improving the patient’s own immune responses. While viruses have a bad reputation for causing death and disease, OVs are incredible tools to help in the fight against cancer. 

Dr. Carmona is postdoctoral research scholar at the Biodesign Center for Personalized Diagnostics at Arizona State University.