Cancer cells

The human immune system serves to detect and destroy abnormal cells in our bodies. Modern medicine uses that system to prevent diseases, like influenza and measles, by injecting vaccines that alert the immune system to be on the lookout for those cells.

The immune system can also detect and destroy some cancer cells, but other cancer cells are able to trick, dodge or destroy immune response.  For example, some cancer cells can change their surface chemistry to make them less detectable; other cancer cells express proteins that deactivate immune response. In the past few years, scientists have developed new methods of treating cancer, called immunotherapy, that foil cancer’s trick by either stimulating the immune system, or by counteracting immune suppression.

Although some of these new treatments hold promise for fighting cancer, there is still much to learn about immunotherapy. For example: Why is immunotherapy effective in some patients but not in others with the same cancer?

In the OSU College of Veterinary Medicine, Dr. Brian Dolan, assistant professor of Biomedical Sciences, is on the forefront of investigation into the use of immunotherapy to fight cancer.

Dolan’s team of investigators includes Ph.D. students in microbiology and molecular and cellular biology, as well as undergraduate students from veterinary medicine. They work in a state-of-the-art laboratory tucked behind the historic facade of the old Poultry Science building. There, Dolan is focused on discovering the mechanisms that allow the immune system to recognize cancer cells as disease.

“We are trying to uncover the secrets of the recognition elements, and how those elements can be enhanced,” he says. “We are also trying to block negative regulators, to make sure the tumor cell is producing components that will mark it as a foreign entity, so it can be targeted for destruction.”

The weapon used in this fight against cancer cells is called a cytotoxic T lymphocyte (CTL). “Your body makes a billion different CTLs,” says Dolan, “and each one could be specific for one thing. That is, one could be specific for a particular virus, one could be specific for another virus, one could be specific for one kind of tumor, and one could be specific for another kind of tumor. It runs the gamut.”

How does it work? CTLs makes chemical ‘puzzle pieces’ that are used as receptors to sense the presence of foreign proteins bound to the body’s own cells. When otherwise healthy cells becomes infected with a virus, or transform into tumor cells, they generate complementary or matching puzzle pieces – that is how the CTL knows what to attack.

A lot of immunotherapy focuses on activating or making more CTLs. The Dolan lab is focused on discovering how the puzzle pieces are generated, and how they match up.

“We are looking at a variety of cellular pathways that, in one way or another, may affect the generation of these puzzle pieces by the tumor cell,” he says. His team recently found they can manipulate these pathways to produce different results. In one case, they found that infecting cancer cells with chlamydia bacteria increased the number of puzzle pieces generated. “The potential is to use this in cases where you want to turn up the pathway so you have more puzzle pieces on the cell surface, increasing the likelihood that a CTL can recognize it and kill it.”

Dolan’s work is in the early stages. The next two steps are to further investigate, and understand, the processes that govern the production of puzzle pieces, and to see if the ‘anti-tumor’ response he got from manipulating a cellular pathway has a beneficial effect in laboratory animals with cancer. If the mice get better, then Dolan envisions collaborating with the Lois Bates Acheson Veterinary Teaching Hospital to develop a compound that can treat dogs and cats with cancer.

The ultimate goal of these investigations is to find cancer treatments that do not have the serious side effects of chemotherapy or radiation. Although Dolan works in the College of Veterinary Medicine, someday his work could also help humans. “There are all kinds of advantages from a One Health standpoint,” says Dolan.” If we find immunotherapies that work well in companion animals, the knowledge gained is very applicable to human medicine.”

Assistant Professor Brian Dolan is investigating the use of immunotherapy to fight cancer.