CSPG4 IgE could attach to and activate immune cells present in the blood of melanoma patients, effectively killing human melanoma cancer cells.

A newly discovered antibody may benefit patients with melanoma who do not respond to current immunotherapies, according to a study presented at the Hybrid Congress in Hamburg organized by the European Academy of Allergy & Clinical Immunology (EAACI). 

Unlike many existing immunotherapies, which belong to the antibody type called IgG, researchers at King's College London and Guy's and St Thomas' have developed an IgE antibody that leverages the patient's own immune system to target cancer in a distinct manner. The team developed a specific IgE antibody for a marker called chondroitin sulfate proteoglycan 4 (CSPG4), which is found on the surface of human melanoma cells in up to 70% of cases. While current immunotherapies broadly activate the immune system, this novel antibody was designed to specifically target immune responses towards melanoma cells.

The researchers demonstrated that CSPG4 IgE could attach to and activate immune cells present in the blood of melanoma patients, effectively killing human melanoma cancer cells. In mice implanted with human immune cells, including cells from melanoma patients, CSPG4 IgE treatment resulted in a slowdown of cancer growth. Furthermore, an allergy test conducted with patient blood indicated that CSPG4 IgE did not activate basophils, a type of white blood cell, suggesting the therapy's potential safety.

"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,” says Dr Heather Bax, Postdoctoral Research Fellow from St. John's Institute of Dermatology, King's College London, in a news release. “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". 

Professor Sophia Karagiannis, from St. John's Institute of Dermatology, King's College London, adds: "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 points 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."