CSPG4

A new class of immunotherapy shows promising results for fighting the most aggressive form of skin cancer. The study, published today in Nature Communications by researchers from King's College London and Guys and St Thomas NHS Foundation Trust, investigates whether a novel antibody can target and treat melanomas. The results show that the antibody activates the immune response to fight cancer and slows melanoma growth in mice. Malignant melanoma is the most aggressive type of skin cancer with poor survival rates for half of patients within five-years of diagnosis. Although there has been substantial progress in developing immunotherapies (drugs which stimulate the bodys own natural defence system to attack cancer), many patients tumours do not respond. This drug could benefit those patients with melanoma who do not respond to existing treatment. Many existing immunotherapies used in cancer treatment belong to the antibody type called IgG. However, researchers at Kings College London and Guy's and St Thomas' have developed an IgE antibody which can utilise the patients own immune system to attack cancer in a different way. Researchers 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. Immunotherapies currently available draw broadly upon the immune systems defences, however this new antibody was designed to target immune responses specifically towards melanoma cells. The researchers showed 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. An allergy test conducted with patient blood found that CSPG4 IgE did not activate white blood cells called basophils, indicating that the therapy may be safe to take. 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, Kings 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 Kings College London and a Consultant at Guys 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 Kings 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 Kings College London in 2017 and has attracted venture capital financing from multiple investors. Chauhan, J., Grandits, M., Palhares, L.C.G.F. et al. Anti-cancer pro-inflammatory effects of an IgE antibody targeting the melanoma-associated antigen chondroitin sulfate proteoglycan 4. Nat Commun 14, 2192, 2023. 10.1038/s41467-023-37811-3