New Study Reveals Potential Link between Mast Cell Activation and Neoantigen Load in Cancers

New Study Reveals Potential Link between Mast Cell Activation and Neoantigen Load in Cancers

Hamburg, Germany 10 June 2023 – A ground-breaking study was presented 10 June at the Hybrid Congress in Hamburg organized by the European Academy of Allergy & Clinical Immunology (EAACI). Study was conducted by researchers from King’s College London and Guy’s and St Thomas’ NHS Foundation Trust has revealed promising results for a new class of immunotherapy in the fight against aggressive skin cancer. The study investigates the efficacy of a novel antibody in targeting and treating melanomas, demonstrating its ability to activate the immune response and impede melanoma growth in mice.

Malignant melanoma, the most aggressive form of skin cancer, poses significant challenges with low survival rates for many patients within five years of diagnosis. While substantial progress has been made in the development of immunotherapies that harness the body’s natural defence system to combat cancer, a significant number of patients fail to respond to existing treatments. The newly discovered antibody holds the potential to benefit patients with melanoma who do not respond to current therapies.

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), 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.

Dr Heather Bax, Postdoctoral Research Fellow from St. John’s Institute of Dermatology, King’s College London, said: “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. Our findings replicate existing observations for MOv18 IgE, the firstanti-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, 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 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.”

Professor James Spicer, from King’s College London and a Consultant at Guy’s and St Thomas’ NHS Foundation Trust, said: “We have recently completed the first ever trial testing an IgE therapy for cancer (MOv18 IgE), and are excited about the prospect of a whole new class of antibody drugs in oncology. The collaboration between the King’s College London and Guy’s and St Thomas’ research groups is close and ever more productive.”

The first IgE antibody (MOv18 IgE) generated at King’s College London has been trialled for ovarian cancer with results expected to be published later in 2023. Epsilogen Ltd owns rights to both CSPG4 IgE and MOv18 IgE. Epsilogen was spun out from King’s College London in 2017 and has attracted venture capital financing from multiple investors.”

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