Scientists focus on a new antibody to fight treatment-resistant cancers

IgG is the commonly used antibody treatment that activates the patient's own immune system against cancer -- also known as immunotherapy. While the therapy is increasingly being seen as an alternative to chemotherapy and radiotherapy as it specifically targets the cancer cells, it is not always effective in some patients with HER2 breast and ovarian cancers and can develop resistance.

The team from King's College London, UK, investigated a different antibody type, IgE, which activates the patient's immune system in different ways than IgG.

As they act on different immune cells to IgG, IgE antibodies uniquely stimulate otherwise inactive immune cells in the 'microenvironment' surrounding the tumour to directly target the cancer cells.

In the study, 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 tumour growth in mice, said Dr Heather Bax from King's College London.

The tumours 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 tumours 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 tumour to suppress an attack, according to the study, published in the Journal for ImmunoTherapy of Cancer (JITC).

"Around 20 per cent 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," said Bax, Postdoctoral Research Fellow in St. John's Institute of Dermatology, at King's.

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