Natural Killers: Using the Body’s Cells to Target Breast Cancer

Study lays groundwork for possible new immunotherapy for the world’s most commonly diagnosed cancer

It sounds like a plot from a Quentin Tarantino movie — something sets off natural killers and sends them on a killing spree.

But instead of characters in a movie, these natural killers are part of the human immune system, and their targets are breast cancer tumor cells. The triggers are fusion proteins developed by Clemson University researchers that link the two together.

“The idea is to use this bifunctional protein to bridge the natural killer cells and breast cancer tumor cells,” said Yanzhang (Charlie) Wei, a professor in the College of Science’s Department of Biological Sciences. “If the two cells are brought close enough together through this receptor ligand connection, the natural killer cells can release what I call killing machinery to have the tumor cells killed.”

It’s a novel approach to developing breast cancer-specific immunotherapy and could lead to new treatment options for the world’s most common cancer. About 1 in 8 women in the U.S. will develop invasive breast cancer during their lives. It is the second leading cause of cancer death in women in the U.S.

Immunotherapy harnesses the power of the body’s immune system to kill cancer cells.

“Very simply, cancer is uncontrolled cell growth. Some cells will become abnormal and have the potential to become cancer,” Wei said. “The immune system can recognize these abnormal cells and destroy them before they become cancer cells. Unfortunately for those who develop cancer, the immune system is not working very well because of gene mutations and environmental factors.”

Most breast cancer targeting therapies target one of three receptors: estrogen, progesterone or epidermal growth factor. However, up to 20 percent of breast cancers do not express these receptors. Wei and his researchers targeted prolactin receptors. Prolactin is a natural hormone in the body and plays a role in breast growth and milk production. More than 90 percent of breast cancer cells express prolactin receptors, including triple-negative breast cancer cells.

One part of the bifunctional protein is a mutated form of prolactin that still binds to the prolactin receptor but blocks signal transduction that would promote tumor growth. The other part is a protein that binds to the prolactin receptor and activates the natural killer cells.

Wei is now seeking funding for an animal model study to confirm the results. If successful, it could move to human clinical trials.

One big question is whether the bifunctional protein will bring natural killer cells to healthy cells in the body that also express prolactin receptors and kill them, too, causing severe side effects.

“It is my dream that someday we can create a group of these bifunctional proteins that could be used for other cancers by shifting the target molecule,” Wei said.