Therapy reawakens immune system to combat pancreatic most cancers

Pancreatic most cancers is notoriously exhausting to deal with and sometimes resists probably the most superior immunotherapies. Northwestern Medicine scientists have uncovered a novel clarification for that resistance: Pancreatic tumors use a sugar-based disguise to cover from the immune system. The scientists additionally created an antibody remedy that blocks the sugar-mediated “don’t-attack” sign.

For the primary time, the group recognized how this sugar trick works and confirmed that blocking it with a monoclonal antibody reawakens immune cells to assault most cancers cells in preclinical mouse fashions.

“It took our team about six years to uncover this novel mechanism, develop the right antibodies and test them,” mentioned research senior writer Mohamed Abdel-Mohsen, affiliate professor of drugs within the division of infectious illnesses at Northwestern University Feinberg School of Medicine. “Seeing it work was a major breakthrough.”

The research was published in the journal Cancer Research (from the American Association for Cancer Research) to mark the beginning of Pancreatic Cancer Awareness Month.

Turning the immune system again on

Pancreatic most cancers is among the many deadliest cancers. It is commonly identified late, with few therapy choices and a five-year survival rate of just 13%. It additionally tends to withstand immunotherapies that work effectively in opposition to different cancers.

Inside pancreatic tumors, the immune system response is unusually suppressed. “We set out to learn why, and whether we could flip that environment, so immune cells attack tumor cells instead of ignoring or even helping them,” Abdel-Mohsen mentioned.

The group discovered that pancreatic tumors hijack a pure security system utilized by wholesome cells. In regular circumstances, wholesome cells categorical a sugar referred to as sialic acid on their floor to sign to the immune system, “don’t harm me.”

The scientists discovered that pancreatic tumors exploit that system by loading the identical sort of sugar onto a floor protein referred to as integrin α3β1. That sugar coat permits the protein to bind to a sensor on immune cells referred to as Siglec-10, sending a false “stand down” sign.

“In short, the tumor sugar-coats itself — a classic wolf-in-sheep’s-clothing move — to escape immune surveillance,” Abdel-Mohsen defined.

Creating a brand new antibody

Once they found this novel hiding mechanism, the Northwestern scientists developed monoclonal antibodies that blocked it. When they used these antibodies within the lab and in two animal fashions, immune cells wakened and started consuming most cancers cells. Tumors in handled mice grew considerably slower than in untreated controls.

Making these antibodies was no small feat. “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 mentioned. 

The tumor sugar-coats itself — a traditional wolf-in-sheep’s-clothing transfer — to flee immune surveillance. ”

The subsequent step, he mentioned, is to mix the antibody with present chemotherapy and immunotherapy therapies. “There’s a strong scientific rationale to believe combination therapy will allow us to reach our ultimate goal: a full remission,” he mentioned. “We don’t want only a 40% tumor reduction or slowing down. We want to remove the cancer altogether.”

Moving towards medical testing

Abdel-Mohsen mentioned his group is now fine-tuning the antibody for human use and shifting towards early security and dosing research. In parallel, they’re testing it together with chemotherapy and immunotherapy and creating a companion take a look at to determine which sufferers’ tumors depend on this sugar-based pathway so clinicians can match the appropriate folks to the appropriate remedy.

Abdel-Mohsen estimates it would take about 5 years earlier than such a remedy might be accessible to sufferers if progress continues as deliberate.

Beyond pancreatic most cancers, the findings may have broader implications, he mentioned. “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.”

Abdel-Mohsen’s lab focuses on the growing field of glyco-immunology, which research how sugars regulate the immune system. “We’re just scratching the surface of this field,” he mentioned. “Here at Northwestern, we’re positioned to turn these sugar-based insights into real treatments for cancer, infectious diseases and aging-related conditions.”

Notes

Abdel-Mohsen is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

This paper was supported partly by Northwestern’s Center for Human Immunobiology Pilot Award, 2025–2026. Abdel-Mohsen can also be supported by National Institutes of Health and the NIH-funded BEAT-HIV Martin Delaney Collaboratory to Cure HIV-1 Infection.