Bringing viruses to the frontlines of cancer treatment

Using viruses to treat cancer.
Some viruses not only have a talent for killing cancer cells, but they also may improve the body’s immune system response to the disease.

As the saying goes, “what doesn’t kill you makes you stronger.” And it turns out that may also be said about one field of cancer research that may seem counterintuitive.

Like cancer, viruses are typically viewed as an enemy to eradicate. But scientists are learning to use some of them as allies in cancer’s treatment. They not only have a talent for killing cancer cells, but also an ability to improve the body’s immune system response to the disease.

Since the late 1800s, doctors have observed that some cancer patients with viral infections go into remission, if only temporarily. Yet while some viruses seemed able to kill tumor cells, researchers couldn’t turn these observations into discovery and treatments until recently. Now, advances in genetic engineering have made it possible to manipulate the genomes of certain viruses, turning them into cancer-killers while priming patients’ immune systems to attack certain cancer cells. Those engineering changes are also designed to neutralize the disease-causing nature of such viruses, rendering them harmless.

Many researchers are hailing these genetically engineered viruses, or oncolytic viruses, as an innovative form of immunotherapy—a type of cancer treatment that harnesses the immune system to fight cancer.

In this article, we’ll explore this new class of therapeutics, including:

If you’ve been diagnosed with cancer and are interested in a second opinion on your diagnosis and treatment plan, call us or chat online with a member of our team.

What is oncolytic virus therapy?

When certain viruses, such as human papillomavirus (HPV), chickenpox or smallpox, are genetically modified and injected into a tumor cell, they make copies of themselves, eventually causing the cell to burst. Not only does that reaction kill the cancer cell itself, but the dying cell also releases substances, such as tumor antigens, that allow the immune system to recognize the type of cell as foreign. The substances released by the dying cancer cells alert the immune system that something is wrong, prompting an attack. This is called oncolytic virus therapy.

To date, the U.S. Food and Drug Administration (FDA) has approved only one oncolytic virus therapy—a genetically modified form of a herpes virus called talimogene laherparepvec (Imylgic®), or T-VEC. It is used to treat certain patients with advanced melanoma that can’t be surgically removed. While T-VEC is the only FDA-approved oncolytic virus so far, clinical trials are underway on many other genetically modified viruses to treat diseases like brain, breast and ovarian cancer.

Clinical trials are currently evaluating the cancer-killing abilities of the viruses listed below.

Adenovirus: A family of common viruses that can cause cold-like symptoms

Herpes simplex virus: A virus that can cause sores on or near the mouth

Maraba virus: A virus found only in insects

Measles: A virus that infects the respiratory tract

Newcastle Disease Virus: A virus found primarily in birds that can cause flu-like symptoms in people

Picornavirus: A family of viruses that can cause a range of diseases

Reovirus: A family of viruses that can affect the gastrointestinal and respiratory tracts

Vaccinia virus: The virus used to help vaccinate against and eliminate smallpox

Vesicular stomatitis virus: A virus that can cause flu-like symptoms

Which types of cancer can viruses attack?

This past spring, City of Hope’s Brain Tumor Program received a $12 million grant from the California Institute for Regenerative Medicine (CIRM) to assess a stem cell-based platform for delivering adenovirus to glioblastoma tumor cells.

Glioblastomas are highly invasive brain tumors that are notoriously difficult to treat. Glioblastomas lack clear boundaries and most chemotherapies have a hard time reaching cancer cells in the brain due to the blood-brain barrier—the natural barrier that protects the brain.

In addition, brain tumors are heterogenous, which means they’re made up of different types of cells and not susceptible to therapies that only target one specific mutation. Oncolytic viruses, on the other hand, can target all malignant cells without harming normal brain tissue.

But how do you protect the virus from the body’s immune system, which is programmed to attack viruses, so it may seek out and kill cancer cells?

To overcome this obstacle, the City of Hope team decided to package the adenovirus within neural stem cells (the nervous system’s stem cells). This effectively shields the virus from the immune system, allowing it to seek out and invade tumor cells—and then alert the body’s immune defenses to cancer’s presence.

In 2018, researchers at Duke University presented findings from a different clinical trial involving an oncolytic virus and glioblastoma. In this trial, investigators showed that using a genetically engineered form of polio virus significantly improved long-term survival rates in patients with recurrent glioblastoma, or glioblastoma that’s returned.

To date, most oncolytic virus therapies have been tested in patients with melanoma or brain tumors, but clinical trials on other types of cancer are emerging. For example, last year, City of Hope launched a clinical trial to determine the effectiveness of VAXINIA, a genetically altered smallpox virus, in patients with advanced solid tumors. The oncolytic virus had been shown to shrink colon, lung, breast, ovarian and pancreatic cancer tumors in previous animal studies.

Combining therapies to fight cancer

Still, the true promise of oncolytic virus therapy may be in its ability to jump-start the immune system. Indeed, researchers have found that these engineered viruses may be helpful when delivered in combination with other treatments—especially alongside checkpoint inhibitor drugs like nivolumab (Opdivo®), ipilimumab (Yervoy®) and pembrolizumab (Keytruda®)—in shrinking solid tumors.

Checkpoint inhibitors are monoclonal antibodies that work by targeting and neutralizing immune checkpoints like CTLA-4 and PD-1, which are pathways tumors use to evade the immune system. Obstructing these checkpoints helps turn on the immune system response against cancer.

Researchers believe that injecting certain patients with an oncolytic virus before delivering a checkpoint inhibitor may enhance the drug’s effect, by improving the immune system’s ability to recognize the cancer cells.

So far, pairing an oncolytic virus with checkpoint inhibitor therapy for colorectal cancer has shown encouraging results in studies. So has pairing an oncolytic virus with a checkpoint inhibitor drug for ovarian cancer. And a recent study demonstrated that the immune-activating effects of T-VEC increased response rates for triple-negative breast cancer tumors when coupled with chemotherapy before surgery.

Oncolytic virus therapy may still be in its infancy, but its impacts are far-reaching. From the accidental discovery of viruses’ cancer-killing abilities to the advances in genetic engineering that led to its combination-therapy potential, oncolytic viruses are an encouraging step forward in the future of cancer treatment.

If you’ve been diagnosed with cancer and are interested in a second opinion on your diagnosis and treatment plan, call us or chat online with a member of our team.