Researchers from King’s College London and Guy’s and St. Thomas’ NHS Foundation Trust report their new class of immunotherapy shows promising results for fighting melanomas, the most aggressive form of skin cancer. The results show that an IgE antibody activates the immune response to fight cancer and slows melanoma growth in mice.

Their study “Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4,” is published in Nature Communications.

“Outcomes for half of patients with melanoma remain poor despite standard-of-care checkpoint inhibitor therapies,” wrote the researchers. “The prevalence of the melanoma-associated antigen chondroitin sulfate proteoglycan 4 (CSPG4) expression is ~70%, therefore effective immunotherapies directed at CSPG4 could benefit many patients. Since IgE exerts potent immune-activating functions in tissues, we engineer a monoclonal IgE antibody with human constant domains recognizing CSPG4 to target melanoma.”

Many existing immunotherapies used in cancer treatment belong to the antibody type called IgG. However, researchers at King’s College London and Guy’s and St. Thomas’ have developed an IgE antibody that can utilize the patient’s own immune system to attack cancer in a different way.

The team developed an IgE antibody specific for a marker on the surface of human melanoma cells, called chondroitin sulfate proteoglycan 4 (CSPG4) found on up to 70% of melanomas.

They demonstrated that CSPG4 IgE could attach to and activate immune cells found in melanoma patient blood to kill human melanoma cancer cells. CSPG4 IgE treatment slowed cancer growth in mice implanted with human immune cells, including cells from patients with melanoma.

“We have shown that an immune response can be triggered by IgE immunotherapy for melanoma and that this applies to human melanomas and to melanoma patient immune responses,” explained Heather Bax, PhD, postdoctoral research fellow from St. John’s Institute of Dermatology, King’s College London. Bax added: “Our findings replicate existing observations for MOv18 IgE, the first anti-cancer IgE, which targets ovarian cancer, and supports development of IgE therapies for other solid tumors.”

Sophia Karagiannis, PhD, professor, St. John’s Institute of Dermatology, King’s College London, said: “Four in ten people with advanced melanoma do not respond to available treatments. Our findings show that the human immune system reacts differently in the presence of drugs based on IgE antibodies and point to the potential of applying IgE to mount an effective response against melanoma. This opens up the possibility of this new class of drugs to benefit different patient groups and a new frontier in the battle against cancer.”

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