Chinese scientists use allergy-like immune response for cancer therapy

HANGZHOU -- Chinese scientists have harnessed one of the human body's fastest and strongest immune responses to develop a potential new weapon to fight cancer, according to a study published in Cell on Wednesday.

The research, led by scientists from Zhejiang University and the First Hospital of China Medical University, focused on mast cells, which are immune cells known for triggering allergic symptoms such as hives and sneezing. Mast cells are loaded with tiny packets of inflammatory molecules and can react within seconds when triggered.

Gu Zhen, a professor at the School of Pharmacy at Zhejiang University and one of the leaders of the research team, said that the overactive immune response inspired the team to explore whether inducing allergic-type reactions in tumors could help overcome tumor immunosuppression.

Instead of allowing mast cells to respond to allergens, the team reprogrammed them using IgE antibodies that recognize proteins found on tumor cells.

When these customized mast cells are injected into the bloodstream, they travel to tumors and unleash sudden bursts of inflammation upon encountering their specific cancer target.

The allergy-like reaction inside the tumor helps activate the immune system and turn quiet, hard-to-treat tumors -- "cold" tumors, which typically evade immune detection -- into "hot" ones that the immune cells can recognize and attack.

The researchers also found that mast cells can serve as living carriers for oncolytic viruses -- viruses that selectively infect and kill cancer cells.

By hiding these viruses inside vesicles of mast cells, the team protected them from being destroyed in the bloodstream. Once the mast cells reached a tumor and became activated, the viruses were released.

In mouse melanoma, breast cancer and lung metastasis test subjects, the approach drew more cancer-killing T cells into the tumor and inhibited tumor growth, according to the study.

This strategy also worked in patient-derived tumor models. Human mast cells equipped with IgE antibodies targeting common tumor marker HER2 and loaded with an oncolytic virus triggered strong T-cell responses and notable tumor suppression, the study found.

"This opens up possibilities for precision therapy in the future," Gu said, adding that matching IgE antibodies to a patient's own cancer markers could rapidly create a personalized therapy.

Beyond oncolytic viruses, mast cells can carry a wide range of therapies, including drugs, proteins, antibodies, and even nanomedicines, and then release them only when they encounter the tumor. The researchers said that the platform could one day support multiple treatment modes within a single cell-based therapy.

The team plans to establish a workflow for the selection of patient-specific IgE antibodies, scale up manufacturing of therapeutic mast cells, and explore combinations with existing cancer immunotherapies, aiming to bring their approach to clinical application as soon as possible, Gu said.