Chinese scientists have turned allergy into a powerful weapon against cancer to deliver drugs and turbocharge the body’s own immune attack on cancer.
The team loaded mast cells – which cause allergic symptoms when they encounter antigens such as seafood and pollen – with anticancer drugs to deliver them into tumours.
The researchers said they were working on clinical applications, including exploring its potential combination with existing cancer immunotherapies.
The scientists from Zhejiang University and the First Hospital of China Medical University published their findings in the peer-reviewed journal Cell last week.
“Our study highlights the translational promise of [immunoglobulin E (IgE)-sensitised mast cells] as an antigen-specific delivery platform for cancer immunotherapy,” they wrote, adding that the new method showed “potential for personalised cancer therapy”.
Mast cells are immune cells that protect the body from pathogens like viruses, bacteria and parasites, as well as toxins such as venom. When they encounter potential dangers, the cells release their stored pro-inflammatory substances to initiate inflammation.
They could also mistake seemingly harmless substances, including peanuts or dust mites, as a threat and cause allergic reactions.
In the study, the Chinese team took advantage of the “over-defence” mechanism to fight cancer.
Co-corresponding author Yu Jicheng, an assistant professor at the College of Pharmaceutical Sciences at Zhejiang University, said: “We attempted to turn tumours into specific allergens that could activate mast cells so that it could guide a targeted immune response.”
The scientists bound IgE antibodies that recognise tumour antigens to the surface of mast cells so they could accurately recognise tumours, he told the Chinese outlet ScienceNet.cn.
They then loaded mast cells with oncolytic viruses that could selectively destroy tumour cells and leave normal cells undamaged.
Once injected into the bloodstream, these engineered mast cells sought out their target tumour and released the inflammatory factors they carried. This recruited immune cells into the tumour micro-environment and stimulated an immune response.
“Mast cells are not only drug delivery platforms, but also amplifiers of the immune response,” Yu said.
“When the viruses break down tumour cells and release tumour antigens, the molecules released by mast cells can recruit immune cells … to enter the tumour. The combination of virus therapy and immunotherapy results in a dual-pronged approach.”
Tests in mouse tumour models of melanoma, lung metastasis and breast cancer showed that their method “induced robust anticancer immune responses and inhibited tumour growth”, the study found.
In patient-derived tumour models, the method was also able to inhibit tumour growth and increase the activity of cancer-killing T cells, according to the paper.
In addition to oncolytic viruses, the mast cell platform could be expanded to carry other payloads, such as small molecules, viruses, proteins, mRNA encapsulated in lipid nanoparticles and drug-loaded nanoparticles for controlled local release, the team wrote.
To personalise the treatment, scientists can also select IgE antibodies based on the specific antigens of different patients’ tumours to bind to the mast cells.
Editor: Zhongxiaowen
