Pancreatic cancer, a notoriously challenging adversary, has long resisted even the most advanced immunotherapies. But a breakthrough discovery by Northwestern Medicine scientists has unveiled a novel strategy to overcome this resistance. The secret to pancreatic cancer's immune evasion lies in a sugar-based disguise, and scientists have developed an innovative antibody therapy to expose and defeat this cunning tactic.
For years, pancreatic tumors have been able to hide from the immune system, but the research team has unraveled the mechanism behind this stealthy behavior. They found that pancreatic cancer cells exploit a natural safety system used by healthy cells, essentially tricking the immune system into ignoring them.
Healthy cells normally express a sugar called sialic acid on their surface, sending a clear message to the immune system: "Don't harm me." However, pancreatic tumors have learned to mimic this strategy, loading the same sugar onto a surface protein called integrin α3β1. This sugar coating allows the protein to bind to a sensor on immune cells, Siglec-10, sending a false signal that tells the immune system to stand down.
"It's a classic wolf-in-sheep's-clothing move," explains study senior author Mohamed Abdel-Mohsen. "The tumor sugar-coats itself to escape immune surveillance, but we've developed a way to expose this deception."
The Northwestern scientists created monoclonal antibodies that block this sugar-mediated "don't-attack" signal. In preclinical mouse models, these antibodies reawakened immune cells, prompting them to attack cancer cells. Treated mice showed significantly slower tumor growth compared to untreated controls.
Developing these antibodies was no easy feat. Abdel-Mohsen notes, "We screened thousands of hybridomas, cells that produce antibodies, before finding the right one."
The team's next steps involve combining the antibody with current chemotherapy and immunotherapy treatments. "There's a strong scientific rationale to believe that combination therapy will lead to full remission," Abdel-Mohsen says. "We're aiming to remove the cancer altogether, not just slow it down or reduce its size."
The scientists are now fine-tuning the antibody for human use and moving towards early safety and dosing studies. Simultaneously, they're testing the antibody in combination with other therapies and developing a companion test to identify patients whose tumors rely on this sugar-based pathway.
Abdel-Mohsen estimates that, with continued progress, this innovative therapy could be available to patients within five years. But the implications of this research extend beyond pancreatic cancer. The team is now investigating whether other hard-to-treat cancers, such as glioblastoma, and non-cancer diseases with immune system involvement, might also employ this sugar-coat trick.
This groundbreaking discovery offers a glimmer of hope in the fight against pancreatic cancer and highlights the potential for innovative antibody therapies to revolutionize cancer treatment.
