Researchers at Zhejiang University have developed a novel method to reprogram mast cells, typically involved in allergies, to deliver cancer-fighting viruses directly to tumors. This approach, detailed in a recent Cell journal study, enhances immune responses and shows promise in animal models. It paves the way for personalized cancer therapies.
Mast cells are a type of white blood cell best known for causing allergic reactions, such as runny noses from pollen or itchy rashes from seafood. A team led by professors Gu Zhen and Yu Jicheng at Zhejiang University, in collaboration with professor Liu Fujian from China Medical University, described in a study published in the journal Cell a method that transforms these cells into vehicles delivering cancer-fighting viruses directly to tumors.
During an allergic reaction, immunoglobulin E (IgE) antibodies bind to mast cells and act as sensors detecting foreign substances. Researchers equipped mast cells with IgE antibodies that recognize specific tumor proteins, reprogramming them to find and target cancer cells. The engineered mast cells were loaded with oncolytic viruses designed to infect and kill cancer cells while sparing healthy ones. Unlike traditional treatments administered through the bloodstream or injected directly into tumors, mast cells protect the viruses during circulation, improving delivery efficiency.
Upon reaching the tumor, the reprogrammed mast cells release the viruses and other immune-activating molecules in a burst similar to an allergic reaction. This delivers a high concentration of therapy precisely where needed, while limiting side effects elsewhere in the body. The reaction also signals other immune cells, including T cells, to join the attack on the tumor. In mouse studies of melanoma, breast cancer, and lung metastasis, the approach slowed tumor growth and improved survival.
"Mast cells are not just carriers of treatment; they amplify the immune response," Yu said. "When viruses break down tumor cells and release tumor proteins, molecules from 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 noted the method could be adapted for personalized cancer treatment, with IgE antibodies designed to target proteins unique to a patient's tumor. In experiments using patient-derived tumor models with high HER2 levels, a protein common in some breast cancers, mast cells carrying anti-HER2 IgE successfully delivered 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' guiding mast cells to the tumor, enabling personalized tumor-allergy immunotherapy."
The mast cell platform could also deliver other treatments, such as small-molecule drugs or antibodies. The team is now working to advance the technology toward clinical use, focusing on improving production, selecting patient-specific IgE antibodies, and exploring combinations with existing immunotherapies.
