First-generation immunotherapy responds poorly to metastatic melanoma. But the Melasphynx team, led by Professor Bruno Segui at the Toulouse Cancer Research Center, is paving the way for new treatments. The Arc Foundation supports this work.
Professor Bruno Segui co-leads the Melasphinx team (CRCT) with Nathalie Andrieu-Abadie and works with Professor Maha Ayyoub who heads the immuno-monitoring department (IUCT Oncopole) and Dr Anne Dejean (Infinity Inserm). The Arc Foundation, which was already supporting its work, has just granted new funding to the team.
You work on metastatic melanoma, what are the characteristics of this cancer?
It is a cancer with a poor prognosis. Fifteen thousand new cases are diagnosed each year in France, and 25% progress to metastatic melanoma. If treatments have improved considerably in ten years, even today, one out of two patients affected by this skin cancer among the most aggressive, does not respond to first generation immunotherapy treatments.
What does your work show?
With the Melasphinx team that I co-lead with Dr. Nathalie Andrieu-Abadie at the Toulouse Cancer Research Center (CRCT), we have identified an inflammatory protein (TNF) and shown that it is involved in resistance to immunotherapies. With Professor Nicolas Meyer, onco-dermatologist specializing in melanoma at the IUCT, we demonstrated that this protein was also very present in patients with metastatic melanoma.
Through two phase 1 clinical trials on limited cohorts of patients, we have therefore co-administered anti-TNFs and immunotherapies targeting immune checkpoints, in order to reactivate lymphocytes (TCD8), capable of killing the cells of melanoma. We have also identified predictive biomarkers for immunotherapies linked to this TNF protein. Between 2019 and 2022, this work received initial funding from the ARC Foundation (450,000 euros) and the Toulouse Cancer Health Foundation (175,000 euros).
What will this new funding of 450,000 euros from the Arc Foundation allow over the period 2023-2025?
After having evaluated and verified the safety and tolerance of the combination of these immunotherapies in patients, this new funding will allow us to deepen our understanding of the mechanisms of resistance to immunotherapy and how to overcome them. We hope to launch a phase 2 multicenter clinical trial starting in 2024.
