Rachel Willand-Charnley, an assistant professor in South Dakota State University's Department of Chemistry and Biochemistry, has received a $100,000 grant to treat colon cancer cells with a glycan therapeutic they developed, targeted at reversing cancer’s ability to thwart immune mediated cytotoxicity via simple sugar residues.
The grant comes by way of the recently established Haarberg Center for Drug, Disease and Delivery Exploratory Grant Program, housed in SDSU's College of Pharmacy and Allied Health Professions.
The Haarberg 3D Center is funded by the South Dakota Board of Regents, with a goal of advancing research commercialization of biomedical technologies through university, industry and clinical collaborations. Recently, the center received a $1.1 million gift from Kevin and Lorie Haarberg and a planned gift of $10 million.
"The focus of this grant has its roots—first and foremost—in the understanding that cancers manipulate communication with your immune system via sugar residues,” Willand-Charnley said. “We have striven to understand how cancers manipulate communication with your immune system via sugar residues on the cell surface and now to prevent that manipulation via our glycan therapeutics."
As Willand-Charnley—an interdisciplinary applied organic chemist who specializes in glycobiology and cancer immunology—explains, all cells in the human body actually "wear" a layer of sugar residue, the glycocalyx.
Why do we care? Why does that matter?
The sugar coat acts as a shield and is our cells' first layer of protection. More importantly, it’s our cells’ first form of communication, Willand-Charnley said.
"The sugar coat is how cells in your body, including cancer cells, communicate with each other," Willand-Charnley said.
Currently, one of the major challenges in cancer treatment, that the RAWC Lab has and is addressing is halting cancer’s ability to use simple sugar residues to manipulate communication with the immune system, a system that would otherwise kill cancer cells. While our immune system would normally "attack" those unhealthy cells, cancer cells can "hide" from our immune system through a specific type of sugar residue the RAWC Lab studies, called sialic acid.
What Willand-Charnley, who studied under Noble laureate Carolyn Bertozzi at the University of California-Berkeley and Stanford University, specializes in the study of sialic acid.
"What we've learned as glyco-cancer immunologists is that cancers overexpress the sugar sialic acid, and for years we didn't really understand what benefit it brought the cancers," Willand-Charnley said. "But thanks to my work and the work of those who have come before me, we understand that by overexpressing sialic acid, it's able to manipulate communication with our immune system."
Basically, sialic acid—through manipulation—allows cancer cells to survive.
Willand-Charnley's grant will develop their antibody-enzyme drug conjugate that will pretreat cancer cells with a specific enzyme which will halt its ability to trick the immune system into believing it is a healthy cell.
Antibody enzyme drug conjugates, Willand-Charnley says, are more promising for cancer treatments than traditional chemotherapeutics because the enzyme that is tethered to an antibody allows for increased cell specificity, reducing off target reactivity with healthy cells. The result of the treatment is the immune system will once again recognize the cancer cell. The therapeutic drug, metaphorically, unmasks the danger that the cancer cell truly is without additionally killing healthy cells.
"By targeting the sugar residues on the cell surface of the cancer that it is utilizing to hide in plain sight," Willand-Charnley explained. "You allow the immune system to correctly identify it—metaphorically—as the wolf in sheep's clothing."
Several types of cancers, including colon cancer, utilize sialic acid. As Willand-Charnley notes, a therapeutic that could reverse the functionality of sialic acid would make significant contributions to the treatment of cancer and subsequent health of cancer patients.