IgE antibodies show promise in targeting HER2 cancers resistant to other therapies

Antibody treatment which activates the patient’s own immune system against cancer, known as immunotherapy, is increasingly being investigated as an alternative for chemotherapy and radiotherapy. This is because it specifically targets the cancer cells, which reduces the side effects seen with more conventional therapies.

Tumors, such as some breast and ovarian cancers, can express the marker HER2. HER2 is responsible for cancer growth and is the target of existing therapies, such as the most commonly used type of antibodies, IgG. However, this treatment is not always effective in some patients.

Now scientists have investigated a different antibody type, IgE, which activates the patient’s immune system in different ways to IgG. As they act on different immune cells to IgG, IgE antibodies uniquely stimulate otherwise inactive immune cells in the ‘microenvironment’ surrounding the tumor to directly target the cancer cells.

In the study, led by Dr Heather Bax at King’s College London, the team engineered IgE versions of existing IgG therapies, and tested their ability to activate immune cells against HER2-expressing cancer cells.

IgE was shown to direct immune cells against HER2-expressing cancer cells, and slowed tumor growth in mice. The tumors grown in mice are known to be resistant to conventional treatments, suggesting this new treatment could be an option for patients who don’t respond to existing therapy.

Further investigation revealed that IgE antibodies stimulated and reprogrammed the ‘immune microenvironment’ around the tumors themselves – shifting from an immunosuppressive to an immunostimulatory response. This means the immune system was activated to target the cancer cells, and to overcome the actions of the tumor to suppress attack.

The study, published in Journal for ImmunoTherapy of Cancer (JITC), with funding from Breast Cancer Now, has shown the potential of IgE as a new therapy for HER2-expressing cancers, including those resistant to other treatments. The researchers believe that, with the right investment and development, this approach could be used in humans in as soon as 3-5 years.

Around 20% of breast and ovarian cancers express the marker, HER2. By generating anti-HER2 IgE antibodies equivalent to the clinically used IgGs, for the first time we demonstrate that IgEs harness unique mechanisms to reprogramme the immune microenvironment, switching immune cells to effectively target HER2-expressing cancers, including those resistant to existing therapies.

Our findings indicate that IgE antibodies could offer a potential new therapy option for patients with HER2-expressing cancer.”

Dr. Heather Bax, Senior Author, Postdoctoral Research Fellow in St. John’s Institute of Dermatology, King’s College London

Co-Author Professor Sophia Karagiannis, Professor of Translational Cancer Immunology and Immunotherapy, in St. John’s Institute of Dermatology, at King’s College London, added: “By generating a panel of IgE antibodies and studying them in different tumor types, we consistently found that the human immune system reacts in the presence of IgE to restrict the growth of cancer.

“The findings of our latest study speak to the potential of applying IgE to stimulate effective responses against hard-to-treat solid tumors. This new class of drugs holds promise to benefit different patient groups and opens a new frontier in the battle against cancer.”

Dr Kotryna Temcinaite, head of research communications and engagement at Breast Cancer Now, who provided funding for the study, said: “This exciting research could lead to much-needed new treatments for people with HER2 positive breast cancer whose cancers don’t respond to existing therapies. Now we know that the treatment works in principle in mice, researchers can continue to develop this immunotherapy to make it suitable for people, as well as to understand the full effect it could have and who it may benefit the most.”