MU researchers continue to retrain immune system to fight cancer after receiving a $3.7 million grant

The study is developing a compound called “fab fragment” that will increase the sensitivity of T cells to cancer cells.

Researchers are striving to develop a new technique of immunotherapy that retrains the immune system to fight cancer. This would serve as an alternative to more conventional approaches like radiotherapy and chemotherapy, that could improve the outcomes for patients not responding to these treatments alone.

A $3.7 million grant from the National Institutes of Health was given to associate professor Dr. Diana Gil Pagés, who is a researcher working on this study at the School of Medicine and the College of Engineering. The grant will help develop a compound called “fab fragment” that will make the T cells in the immune system more sensitive to cancer cells.

The researchers take antibodies and remove the “fabs.” Antibodies are proteins that can target destructive molecules in the body, including bacteria and viruses.

“The fabs are kind of the Velcro that the antibody molecules use to stick to whatever is the target. We use fabs that stick to T cells, not to destroy them in this case but to manipulate them,” Gil Pagés said.

T cells have an important role in the immune system recognizing any cell in the body that may be infected or damaged. That includes cancer cells. However, cancer cells usually evade T cell response by multiple strategies that allow them to remain undetected. By adding the fab, T cells will be able to recognize cancer cells more strongly.

“You think T cell is like the police,” graduate student Hien Huynh said. “The fab we add in gives the police clear glasses [to] see the cancer cells as something it has to attack.”

T cells have trouble recognizing cancer cells because cancer is the body’s own cells mutated instead of something foreign. T cells also have weak antigen recognition in regard to cancer cells. Antigens are foreign bacteria or viruses that invade the body.

“So we are using these fabs that when they bind to the T cells, it makes them more sensitive to identify infection,” Gil Pagés said.

On the other hand, what makes this study tricky is that researchers must find a balance.

“It’s very important for T cells to distinguish between healthy tissue and unhealthy tissue, and if you play with their sensitivity, as we are doing, you may curve the line and make the T cells react to healthy tissue as well as cancer or infected tissue,” Gil Pagés said. “That’s when you run into autoimmune effects of the treatment.”

Huynh, who is working on the study with Gil Pagés, said they have to be cautious to not block where antigens are detected on the T cell when they add the fab. They also can’t stimulate the T cell when tumor antigens have not been engaged on the T cells, thus the T cells will not target nonspecific cells.

It will be years until the study is ready to move onto human trials. Gil Pagés and her staff are currently working on mice. They must first put human reagents in a mouse to simulate the effects on humans. Once they validate their findings, they can then develop a fab that is safe for humans.

“Right now, we are starting our studies with humanized mice,” Dr. Gil Pagés said. “We are trying to identify the best fab fragment to deliver this type of treatment to humans.”

If the study is successful, the fab fragment will help enable the immune system to fight off cancer. However, immunotherapy will not be able to fight off cancer alone. It will have to be paired with chemotherapy and other treatments to obtain the best results.

The grant will ultimately fund the salary for personnel on the study, mice, reagents and lab services. The grant is part of the NIH “Cancer Moonshot Research Initiatives,” which strives to make a decade’s worth of cancer research progress in five years.

Edited by Laura Evans | levans@themaneater.com

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