Vaccine Research Targets Cancer Cells

Potential new cancer treatment boosts immune system

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Byram Bridle

Breakthroughs often happen when scientific fields are bridged, says Prof. Byram Bridle, a viral immunologist who joined the pathobiology department in January. And he believes he may have discovered one: Bridle’s research bridges virology and immunology and may be the foundation for a very promising new approach to treating cancer.

Here’s how it works. Bridle started out studying immunological strategies for fighting cancer. “We all have cancer cells showing up in our body from time to time,” he explains, “but usually our immune system gets rid of them. It’s designed to protect us from things that are dangerous, including cancer.” And most of the time, it works. Only a small percentage of cells escape from the immune system and develop into tumours.

Clearly, the body’s natural response was not enough in those cases, so immunologists have been looking for ways to, in Bridle’s words, “hyperactivate the immune system.”

Bridle’s research involved using vaccinations to accomplish this. “Just like when you have a flu vaccination, the ingredients in the vaccine show the immune system what to look for and what to attack. In the cancer vaccine, we take specific proteins from the cancer cells that are different or expressed in larger amounts than in normal cells, and use them in a vaccine. That tells the immune system ‘this is what your tumour looks like, go do a better job of getting rid of it.’”

Early studies used proteins taken from the cells in the patient’s actual tumour, but Bridle says ongoing research is finding that certain proteins are produced by many types of cancer, so that more generic vaccines can be produced.

There are some challenges, of course. One is the risk that this vaccine could cause normal cells to be attacked. In fact, this side effect has been seen when immunotherapy is used to treat skin cancer; when normal cells are also killed, the patient develops white patches on the skin called vitiligo. “This is an acceptable trade-off for curing skin cancer,” Bridle says, “but when you’re treating brain cancer, for example, you can’t afford to also be killing normal cells.” Therefore, in practising due diligence, Bridle’s research also incorporates studies to determine how to prevent autoimmune pathology.

Bridle discovered that other research might hold some answers. Sometimes when people with cancer are infected with a virus, the virus also attacks the cancerous tumours and destroys them. Some viruses, it turns out, actually prefer to invade cancerous cells, and researchers are identifying those that will kill cancer cells while ignoring normal ones. These are called oncolytic viruses.

The problem: the immune system is very good at finding and destroying viruses, often preventing them from getting rid of the cancer.

“With my research, I found a way to combine these two treatments,” explains Bridle. “My goal was to combine the benefits of the two approaches, but I was actually able to see a synergistic effect, where the benefits don’t just add together, they are multiplied.”

Bridle’s strategy involves first vaccinating the patient with the cancer-specific protein to activate the immune system against the cancer cells. Then, after a period of time, he takes the gene encoding that protein, puts it in the oncolytic virus and injects the modified virus into the patient.

Because the immune system has already been sensitized by the first vaccination, it reacts more to the tumor protein expressed by the virus than to the virus itself. The virus can now sneak in under the radar to attack the cancer cells, and the ensuing, massive immune response also attacks the cancer.

Bridle has modified the treatment to include a drug known as a histone deacetylase inhibitor to modulate both the oncolytic and immunological components. Adding this drug makes the treatment more effective at killing the cancer cells while simultaneously reducing the problem of normal cells being attacked by the immune system. “Another good aspect of this is that both the viruses and the immune system will search out cancer cells all over the body. Even if just a few cells have spread, they can find them and destroy them,” Bridle says.

Bridle’s treatment has been tested on mice with cancers that were considered incurable. Almost all the mice were cured.

Of course, curing mice is a long way from curing people, and that’s why Bridle has chosen to return to U of G. “Here I can work with dogs and cats at the Institute for Comparative Cancer Investigation and refine the treatment,” he says.

He hopes not only to effectively treat pets with cancer, but to pave the way for testing on people. Dogs and cats are ideal for his studies at this point because they vary considerably in size and genetics, and live in different environments, just as people do. “Companion animals are good sentinels of human disease.

“If we can refine this, it may be that with as little as a couple of vaccinations, we can effectively treat cancers without all the toxic side-effects of some other treatments,” Bridle says. He emphasizes that he doesn’t want to be critical of chemotherapy and radiation, which have saved many lives, but he can’t help but be excited about the promise of his new approach, and he’s delighted to be bringing it to U of G.

That’s in part because it’s his alma mater: Bridle did his undergraduate work here and earned his PhD before spending several years at McMaster University in the McMaster Immunology Research Centre on a post-doc fellowship.

He lives in Guelph with his wife and two young sons. “We love the outdoors, and spend time wilderness canoeing and camping every summer,” Bridle says. “My older son was carrying his own pack at three.” Bridle also confesses to a passion for hockey and looks forward to playing this winter.