Allergy Cells to Deliver Oncolytic Viruses or Drugs and to Stimulate the Immune System

A team of scientists in China has found a way to turn the same type of cells that cause allergies into a new kind of weapon against cancer. Their work suggests that the body’s fastest immune reaction, normally blamed for hives and asthma, could be redirected to wake up the immune system inside tumors and help other cancer treatments work better.

The research was led by scientists at Zhejiang University and the First Hospital of China Medical University and was recently published in the journal Cell. The core idea is to reprogram mast cells, which are immune cells best known for their role in allergic reactions, so that they attack cancer instead of reacting to pollen, foods or dust mites. Mast cells sit in tissues like the skin, lungs and gut, packed with tiny granules full of powerful inflammatory chemicals that they can release within seconds. This “rapid response” nature makes them an attractive tool if they can be guided safely and precisely to tumors.

To redirect mast cells, the team used IgE antibodies, the same type of antibody that normally recognizes allergens and sets off allergies. Instead of IgE that binds to dust or food proteins, they attached IgE that recognizes proteins present on the surface of cancer cells, such as HER2 in some breast cancers. When mast cells are “sensitized” with this tumor‑specific IgE, they effectively become programmed to see the tumor as if it were an allergen. Once these engineered cells are infused into the bloodstream, they tend to home in on tumors that display the matching antigen, then become activated and release a burst of inflammatory signals right inside the cancer. This local, allergy‑like reaction changes the character of the tumor environment. Many solid tumors are considered “cold,” meaning they are invisible or uninteresting to T cells and other immune cells that could kill them. By suddenly flooding the tumor with mast‑cell mediators and chemokines, the engineered cells turn these cold tumors into “hot” ones, making them more visible and attractive to cancer‑killing T cells. In preclinical experiments in mice, this approach increased the number of T cells entering the tumor and slowed tumor growth.

The team went a step further and used mast cells not only as signal amplifiers but also as living delivery vehicles for cancer‑killing viruses. These viruses, called oncolytic viruses, are designed to infect and destroy cancer cells while sparing normal tissue, but in the bloodstream they are vulnerable to immune clearance and neutralization. By loading oncolytic adenoviruses into the granules of mast cells, the researchers could hide the viruses during circulation and then release them only when the mast cells were activated inside the tumor. In mouse models of melanoma, breast cancer and lung metastases, this combined strategy attracted more T cells into the tumor and led to better control of tumor growth than using viruses alone.
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Importantly, the concept was also tested in a more human‑like context. The scientists used “humanized” models with patient‑derived tumors that overexpress HER2, a receptor often found in aggressive breast cancer. Human mast cells were armed with IgE that targets HER2 and were loaded with oncolytic virus, then applied to these HER2‑positive tumors. The treatment increased T‑cell activity in the tumors and reduced their growth, suggesting that the same principles might be adapted to real patients if the right tumor markers and matching IgE antibodies are chosen.

One of the most promising aspects of this work is its potential for personalization. In theory, for each patient, doctors could identify key antigens on that person’s tumor and then generate IgE antibodies that recognize those antigens. Mast cells from a suitable source could then be sensitized with these patient‑specific IgE molecules and loaded with the chosen therapeutic cargo, whether it is an oncolytic virus, a drug, a protein or even a nanomedicine. This could lead to a “mix and match” cell therapy platform, where the same type of engineered mast cell can carry different payloads and be tailored to different tumor targets.

The approach also fits well with existing cancer immunotherapies. Many patients do not respond to checkpoint inhibitors and other immune drugs because their tumors remain cold, with very few immune cells inside. By converting tumors into hot ones, mast‑cell‑based therapies might make more patients eligible for benefit from these established drugs, working in combination rather than replacing them. The research teams have said that exploring such combinations is one of their future goals, along with building practical methods for choosing IgE antibodies and scaling up manufacturing of therapeutic mast cells.

Source.