Natural killers: Using the body’s cells to target breast cancer, Clemson researchers link both – Florence, South Carolina

Florence, South Carolina 2021-09-17 11:23:57 –

It sounds like a Quentin Tarantino movie plot — something that complements a natural killer and sends it to a hitman.

However, instead of the characters in the movie, these natural killer are part of the human immune system and their target is breast cancer tumor cells. The trigger is a fusion protein developed by researchers at Clemson University that connects the two.

“The idea is to use this bifunctional protein to bridge natural killer cells and breast cancer tumor cells,” said Professor Yanzhang (Charlie) Wei. Faculty of Science Department of Biological Sciences.. “When the two cells are close enough together through this receptor ligand connection, natural killer cells can release what I call the killing mechanism and kill tumor cells.”

This is a new approach to developing breast cancer-specific immunotherapy and may lead to new treatment options for the most common cancers in the world.

In the United States, about 1 in 8 women and 1 in 1,000 men develop invasive breast cancer in their lifetime. Breast cancer is the second most common cause of cancer deaths in women in the United States, second only to lung cancer. NS American Cancer Society It is estimated that about 43,600 US women will die of the disease this year.

Immunotherapy uses the power of the body’s immune system to kill cancer cells.
“Very simply, cancer is uncontrolled cell proliferation. Some cells can become abnormal and become cancerous,” 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 due to genetic mutations and environmental factors. It’s not working very well.

As a result, cancer cells have won the battle between the immune system and the tumor. “
Most breast cancer targeting therapies target either the estrogen receptor, the progesterone receptor, or the epidermal growth factor receptor. However, up to 20 percent of breast cancers do not express these receptors. These cancers are known as triple-negative breast cancers. Triple negatives are the most deadly subtype of breast cancer due to high heterogeneity, high metastatic frequency, early recurrence after standard chemotherapy, and lack of efficient treatment options.

In this new study, Wei and his researchers targeted the prolactin receptor. Prolactin is a natural hormone in the body that plays a role in breast growth and lactation during lactation. Breast cancer cells overexpress prolactin receptors.

“It’s not good news when people are diagnosed with breast cancer and it’s called triple negative,” Way said. “This may give the patient another option.”

Over 90% of breast cancer cells, including triple-negative breast cancer cells, express the prolactin receptor.

Wei and his team have developed a bifunctional protein. Some are variants of prolactin that can bind to prolactin receptors but block signaling that promotes tumor growth. The other part is the extracellular domain of major histocompatibility complex class I chain-related proteins (MICA).

When MICA binds to the prolactin receptor, natural killer cells are activated.

“One of the things tumor cells do is to inhibit the activation of natural killer cells, so these artificial bifunctional proteins are used to connect and activate natural killer cells for cytotoxicity. Promotes the death of breast cancer cells without increasing the number of cells, “said Wei.

Wei is currently seeking funding for animal model research to confirm the results.

One of the big questions is whether bifunctional proteins bring natural killer cells to healthy cells in the body, and also express prolactin receptors to kill them, causing serious side effects.

If animal model studies are successful, potential new therapies may move to human clinical trials.

“If we now have the money and everything is what we expected in animal model research, we could enter clinical trials in five or six years,” he said. .. Wei said that the protein created by Clemson researchers uses human natural killer cells and breast cancer cells, so the conversion from in vitro and animal studies to clinical trials has this potential more than others in the past. He said he hoped it would be easier for immunotherapy.

Developing new immunotherapies for cancer is nothing new to Wei. His work combining tumor cells with dendritic cells, an important part of the body’s adaptive immune system, has proven effective in patients with melanoma, renal cell carcinoma, and neuroblastoma. It led to a cell vaccine. The vaccine has been patented and licensed to three biotechnology companies. The two companies are still pursuing vaccine therapy or related therapies.

“One day, my dream is to be able to create a group of these bifunctional proteins that can be used in other cancers by shifting the target molecule. Some of the bifunctional proteins that target natural killer cells. There are other parts that will target other types of cancer with unique markers, “Wei said.

PLOS One is a peer-reviewed scientific journal published by the Public Library of Science that recently published a study of Wei’s breast cancer and natural killer cells.the title is “MICA-G129R: Bifunctional fusion protein increases PRLR-positive breast cancer cell death in co-culture with natural killer cells.”

Hui Ding, a PhD graduate of Clemson, is the lead author of this treatise. Other authors include Garrett Buzzard, a PhD student at Clemson. Clemson Research Assistant Sisi Huang; Michael Sehorn, Associate Professor, Department of Genetics and Biochemistry, Clemson University. Ken Marcus, a professor of Clemson chemistry.

This study was partially supported by the Clemson Support for Early Exploration and Development (SEED) Grant (CU SEED2017).

Natural killers: Using the body’s cells to target breast cancer, Clemson researchers link both Source link Natural killers: Using the body’s cells to target breast cancer, Clemson researchers link both

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