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.


New video series puts discussion ‘On the Table’ and in your pocket

Clemson has launched a new video series that puts experts on your screen when and where you want them. “On the Table,” a public policy series from ClemsonTV, tackles such tough subjects as concussions in sports, the role of technology in our lives and health screening disparities, providing in-depth discussion from leading researchers and scholars who are members of the Clemson faculty.

“We wanted to put topics on the table, figuratively and literally, with something very visual to represent the topic,” says ClemsonTV director Jacob Barker. “The web is flooded with how-to videos, but there is very little to offer in the way of substantive discussion. We wanted to combine expert information with the flexibility of on-demand viewing.”
Each episode is hosted by Peter Kent, a career journalist and former science writer at Clemson. The first three episodes are available now, with several more in production.

In episode one, “Protecting Against Concussions,” Greg Batt, an assistant professor in food, nutrition and packaging, and John DesJardins, an associate professor in bioengineering, explain their work with the national Head Health Initiative on three challenges: finding better tools for doctors to detect brain injury; creating new ways to monitor head impacts as they happen; and developing improved, energy-absorbing and energy-reducing materials.

The second episode, “To Trust or Not To Trust,” features Richard Pak, an associate professor in psychology and his research on the relationship between humans and the technology that makes hundreds of hidden decisions in our lives every day. The outcomes can be beneficial, such as self-driving cars that improve highway safety and driving efficiency. Sometimes, however, they can be detrimental. Are we trusting technology enough or too much?

In episode three, “Witness Breast Cancer Awareness,” Rachel Mayo, a professor in public health sciences, talks about the power of a personal experience that led her to launch the South Carolina Witness Project, part of the National Witness Project. The effort, a network of survivors and community-based organizations, aims to eliminate the disparity of breast and cervical cancer diagnoses and deaths: Black women are more likely to have mammograms, but much more likely to die of breast cancer. Mayo’s research shows that how information is presented makes a difference.

Yet another episode looks at Wade Foster.
Wade Foster was 13 when he helped to build a university he could never attend. His children could never attend. His grandchildren could never attend. Foster was a criminal; a black boy caught stealing six dollars worth of clothes from a white family. Sentenced to six months in prison, South Carolina gave Foster to Clemson University to serve his sentence as convict labor. South Carolina called convict labor “slaves of the state.”
Rhondda Thomas, associate professor of African American Literature at Clemson, sheds light on the slaves who labored to build the institution and why it’s necessary to paint the full picture of a school’s history.
Thomas joined the university in 2007 and teaches African American literature in the English department. She is the author of “Exodus: A Cultural History of Afro-Atlantic Identity, 1774-1903 and the editor of Jane Edna Hunter’s autobiography, “A Nickel and a Prayer.” In 2013, she co-edited “The South Carolina Roots of African American Thought” with Clemson professor of English Susanna Ashton.
Last year she received a grant for her research about African Americans who lived and labored on Clemson land during the pre-1963 integration period. James E. Bostic Jr. and Edith H. Bostic of Atlanta awarded Thomas $50,000. That gift was matched by the university, bringing the total grant to $100,000.

My Clemson: Diana Ivankovic

Diana Ivankovic PhD ’95


My husband and I were high school sweethearts when we came to the U.S. from Croatia in 1986 to pursue college degrees. In 1989, with a B.S. in biology and postgraduate training at Greenwood Genetic Center, I joined Miren at Clemson to pursue a graduate degree in microbiology. With a 3-year-old (Sven) and another on the way (Andre), we both walked across the stage of Littlejohn in 1995 to receive our Ph.Ds.
Since then, I have worked as a laboratory coordinator and visiting lecturer at Clemson, become a full professor at Anderson University, had two more children, established the Center for Cancer Research and survived breast cancer. I still teach in Clemson’s summer science program and collaborate with Clemson researchers.
Because of my experience with breast cancer, as well as my mother’s, I have a passion for finding a cure. That’s why I counsel newly diagnosed patients. It’s why I served for many years on the board of the Susan G. Komen Foundation. It’s why I travel abroad with students, even working with shamans in the Peruvian Amazon, searching for new anti-carcinogenic plant extracts. It’s why I work with students at the Center for Cancer Research, trying to inspire my students and fellow researchers to collaborate, share, work together and aim for the stars.
Ivankovic is a professor of biology and the James Henderson director of the Center for Cancer Research at Anderson University, which recently was the recipient of a grant from Coach Dabo Swinney’s All In Team Foundation in support of its breast cancer research.