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A new immune-activating antibody therapy has shown potential for shrinking treatment-resistant breast and ovarian cancers, according to a study from King’s College London. The research, published in Journal for ImmunoTherapy of Cancer, reveals that IgE antibodies can stimulate the immune system to attack HER2-positive tumors, potentially offering a new treatment for patients who do not respond to existing HER2-targeted therapies.
A new approach to targeting HER2 cancers
HER2-positive breast and ovarian cancers are often treated with IgG-based antibody therapies, such as trastuzumab (Herceptin) and pertuzumab. These antibodies target the HER2 protein on cancer cells and trigger an immune response, but some tumors develop resistance, making treatment ineffective.
The research team, led by Heather Bax, PhD, a postdoctoral research fellow at King’s College London, explored an alternative type of antibody—IgE, which interacts with the immune system differently than IgG. While IgG antibodies primarily activate immune cells circulating in the bloodstream, IgE antibodies engage immune cells found in tissues, particularly in the tumor’s microenvironment, potentially making them more effective against solid tumors.
“By generating anti-HER2 IgE antibodies equivalent to the clinically used IgGs, for the first time we demonstrate that IgEs harness unique mechanisms to reprogram the immune microenvironment, switching immune cells to effectively target HER2-expressing cancers, including those resistant to existing therapies,” said Bax.
Stronger immune activation and tumor shrinkage
The researchers engineered IgE versions of trastuzumab and pertuzumab and tested their ability to activate immune cells against HER2-positive tumors. Their findings include:
- IgE antibodies reprogrammed the tumor’s immune environment, shifting it from an immunosuppressive to an immunostimulatory state.
- Monocytes exposed to IgE produced more pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β), which help destroy cancer cells.
- In two trastuzumab-resistant HER2-positive tumor models, IgE therapy significantly slowed tumor growth in mice with humanized immune systems.
- The treatment increased the infiltration of beneficial immune cells into tumors, particularly activated T cells, while reducing immunosuppressive cells.
Co-author professor Sophia Karagiannis emphasized the broader impact of these findings: “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.”
Potential for future cancer treatments
HER2-positive breast cancer accounts for about 20% of breast and ovarian cancers, and many patients develop resistance to existing HER2-targeted drugs. These findings suggest that IgE-based therapies could provide a new option for these hard-to-treat cancers.
“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,” said Kotryna Temcinaite, PhD, head of research communications at Breast Cancer Now, which funded the study.
With further development and clinical trials, IgE-based immunotherapy could be available for patients within the next 3–5 years, offering a new strategy for tackling HER2-driven tumors that resist conventional approaches.
