Scientists alter mast cells to fight cancerous tumors

Scientists at Zhejiang University have found a way to turn allergy-causing cells in the body into cancer-fighting agents, offering a new targeted approach that combines immune system activation with precise delivery of cancer treatments.

Mast cells, a type of white blood cell, are best known for causing allergic reactions, such as runny noses from pollen or itchy rashes from seafood. Researchers have now discovered how to redirect these cells' rapid response to attack tumors instead.

In a study published in the journal Cell, a team led by professors Gu Zhen and Yu Jicheng of Zhejiang University, in collaboration with professor Liu Fujian of China Medical University, described a method that transforms mast cells into vehicles that deliver cancer-fighting viruses directly to tumors.

During an allergic reaction, antibodies called immunoglobulin E, or IgE, bind to mast cells and act like sensors, detecting foreign substances. In this study, researchers equipped mast cells with IgE antibodies that recognize specific tumor proteins, effectively reprogramming them to find and target cancer cells.

Once engineered, the mast cells were loaded with oncolytic viruses, which are designed to infect and kill cancer cells while sparing healthy ones. Unlike traditional cancer treatments given through the bloodstream or injected directly into tumors, the mast cells protect the viruses during circulation, improving delivery efficiency.

When the reprogrammed mast cells reach the tumor, they release the viruses and other immune-activating molecules in a burst similar to an allergic reaction. This delivers a high concentration of the therapy right where it is needed, while limiting side effects throughout the body.

The reaction also signals other immune cells, including T cells, to join the attack against the tumor. In mice studies of melanoma, breast cancer, and lung metastasis, this approach slowed tumor growth and improved survival.

"Mast cells are not just carriers of treatment; they amplify the immune response," Yu said. "When the viruses break down tumor cells and release tumor proteins, the molecules released by mast cells recruit immune cells, such as CD8+ T cells, into the tumor. This creates a double attack combining virus therapy and immunotherapy."

The researchers said the method could be adapted for personalized cancer treatment. The IgE antibodies can be designed to target proteins unique to a patient's tumor, allowing the therapy to be tailored for each individual.

In experiments using patient-derived tumor models with high levels of HER2, a protein common in some breast cancers, mast cells carrying anti-HER2 IgE successfully delivered the viruses and triggered strong immune responses, leading to noticeable tumor shrinkage.

"This opens the door for future precision therapy," Gu said. "Tumor proteins from each patient could act like the 'allergic signal' that guides mast cells to the tumor, enabling a personalized tumor-allergy immunotherapy."

The mast cell platform could also be used to deliver other treatments, such as small-molecule drugs or antibodies. The team is now working to move the technology toward clinical use, focusing on improving production, selecting patient-specific IgE antibodies, and exploring combinations with existing immunotherapies.