Pancreatic cancer remains one of the most lethal forms of cancer, with a five-year survival rate of just 13%. The disease is often diagnosed at a late stage and shows resistance to existing immunotherapies. Researchers at Northwestern Medicine have identified a mechanism that helps pancreatic tumors evade detection by the immune system and developed an experimental antibody therapy to counteract this effect.
The study, led by Mohamed Abdel-Mohsen, associate professor of medicine in the division of infectious diseases at Northwestern University Feinberg School of Medicine, revealed that pancreatic tumor cells use a sugar-based coating to avoid immune attack. “It took our team about six years to uncover this novel mechanism, develop the right antibodies and test them,” Abdel-Mohsen said. “Seeing it work was a major breakthrough.”
Healthy cells typically display sialic acid on their surfaces as a signal for immune cells not to attack. Pancreatic tumors mimic this process by adding sialic acid to a surface protein called integrin α3β1. This modification allows tumor cells to bind with Siglec-10 sensors on immune cells, sending a misleading "stand down" message.
“In short, the tumor sugar-coats itself — a classic wolf-in-sheep’s-clothing move — to escape immune surveillance,” Abdel-Mohsen explained.
After identifying this evasion tactic, the Northwestern team developed monoclonal antibodies designed to block it. In laboratory experiments and two animal models, these antibodies reactivated immune cells so they could target and destroy cancer cells. Tumors in treated mice grew more slowly than those in untreated controls.
Making these antibodies involved extensive screening efforts. “When you make an antibody, you test what are called hybridomas, cells that produce antibodies. We screened thousands before finding the one that worked,” Abdel-Mohsen said.
Looking ahead, researchers plan to combine their antibody therapy with existing chemotherapy and immunotherapy regimens. “There’s a strong scientific rationale to believe combination therapy will allow us to reach our ultimate goal: a full remission,” Abdel-Mohsen stated. “We don’t want only a 40% tumor reduction or slowing down. We want to remove the cancer altogether.”
The research team is currently refining the antibody for potential human use and preparing for early safety and dosing studies. They are also developing diagnostic tests aimed at identifying patients whose tumors rely on this sugar-based pathway so clinicians can match treatments accordingly.
Abdel-Mohsen estimates that if progress continues as planned, it may take about five years before such therapies become available for patients.
Beyond pancreatic cancer, scientists are investigating whether similar sugar-based mechanisms might be present in other difficult-to-treat cancers like glioblastoma or even non-cancer diseases involving immune system misdirection.
Abdel-Mohsen’s lab specializes in glyco-immunology—the study of how sugars regulate immunity—and aims to translate these findings into new treatments for various conditions including cancer and infectious diseases. “We’re just scratching the surface of this field,” he said. “Here at Northwestern, we’re positioned to turn these sugar-based insights into real treatments for cancer, infectious diseases and aging-related conditions.”
Abdel-Mohsen is affiliated with the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. The study received support from Northwestern University’s Center for Human Immunobiology Pilot Award (2025–2026) as well as several grants from the National Institutes of Health.