Researchers have discovered that pancreatic tumours evade the immune system by disguising themselves with a sugar coating. To combat this, they have developed a new antibody therapy that blocks this ‘don’t-attack’ signal, which slows tumour growth.
Scientists at Northwestern Medicine have discovered that tumours cloak themselves in a sugar-based disguise that prevents the immune system from attacking, a key reasons why pancreatic cancer is so resistant to treatment. The study details the development of an antibody therapy that blocks this sugar-mediated ‘don’t-attack’ signal, potentially allowing for new therapies to be developed in future.
For the first time, researchers identified precisely how this sugar trick works and demonstrated in preclinical mouse models that blocking it with a monoclonal antibody reawakens immune cells to target cancer cells.
“It took our team about six years to uncover this novel mechanism, develop the right antibodies and test them,” said study senior author Mohamed Abdel-Mohsen, Associate Professor of Medicine in the Division of Infectious Diseases at Northwestern University Feinberg School of Medicine. “Seeing it work was a major breakthrough.”
Turning the immune system back on
Pancreatic cancer is one of the deadliest forms of cancer, often diagnosed at an advanced stage with limited treatment options and a five-year survival rate of just 13 percent. It also shows unusual resistance to immunotherapies that are effective against other cancers.
Pancreatic cancer is one of the deadliest forms of cancer, often diagnosed at an advanced stage with limited treatment options and a five-year survival rate of just 13 percent.
“Inside pancreatic tumours, the immune system response is unusually suppressed. We set out to learn why, and whether we could flip that environment, so immune cells attack tumour cells instead of ignoring or even helping them,” Abdel-Mohsen said.
The team discovered that pancreatic tumours hijack a natural safety system used by healthy cells. Normally, cells display a sugar called sialic acid on their surface, signalling to the immune system not to harm it. Pancreatic tumours exploit this system by coating a surface protein called integrin α3β1 with the same sugar. This allows the protein to bind to a sensor on immune cells known as Siglec-10, sending a false ‘stand down’ signal.
“In short, the tumour sugar-coats itself – a classic wolf-in-sheep’s-clothing move – to escape immune surveillance,” Abdel-Mohsen explained.
Creating a new antibody
After finding this mechanism, the team developed monoclonal antibodies to block it. When tested in the lab and in two animal models, the antibodies reactivated immune cells, which began attacking cancer cells. Tumours in treated mice then grew significantly slower than in untreated controls.
“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. “There’s a strong scientific rationale to believe combination therapy will allow us to reach our ultimate goal: a full remission. We don’t want only a 40 percent tumour reduction or slowing down. We want to remove the cancer altogether.”
Moving toward clinical testing
The team is now refining the antibody for human use and planning early safety and dosing studies. Parallel work includes combining it with existing chemotherapy and immunotherapy and developing a companion test to identify which patients’ tumours rely on this sugar-based pathway. Abdel-Mohsen estimates that if progress continues as planned, such a therapy could reach patients in around five years.
The team is now refining the antibody for human use and planning early safety and dosing studies.
Beyond pancreatic cancer, the findings could have wider implications too. “We’re now asking whether the same sugar-coat trick shows up in other hard-to-treat cancers, such as glioblastoma, and in non-cancer diseases where the immune system is misled,” he said.
“We’re just scratching the surface of this field,” he added. “Here at Northwestern, we’re positioned to turn these sugar-based insights into real treatments for cancer, infectious diseases and aging-related conditions.”