
24 Jan Major funding from the Institut National du Cancer – Pediatric hepatic oncogenesis and immunotherapy project – Aksam Merched – team 6 MIRCADE
Aksam Merched, a professor with the Mircade team at BRIC, led by Christophe Grosset, has secured major funding of €600,000 from the National Cancer Institute (INCa). He is one of just four winners selected under the call for projects aimed at “supporting particularly innovative initiatives in pediatric immuno-oncology.” The project, titled “Innovative Targets in Pediatric Hepatic Oncogenesis, Immunosuppression, and Resistance to Immunotherapy,” is being conducted in collaboration with Valérie Desvergnes, a CNRS research director, and their BANCO group within the ARNA unit (U1212 – CNRS UMR 5320), directed by Philippe Barthélémy.

Team 6 MIRCADE – BRIC
Objective of the project
The primary objective of the project is to develop innovative immunotherapies targeting mRNA to treat hepatoblastoma (HB), the most common malignant liver tumor in children. Currently, the 5-year survival rate for HB is approximately 80%, achieved through a combination of cisplatin-based chemotherapy and surgery. However, this treatment protocol is frequently associated with severe complications, relapses, and resistance to chemotherapy, particularly in high-risk patients whose prognosis remains poor. These challenges underscore the urgent need for safer and more effective therapeutic options.
Scientific innovations
Recent research by Aksam Merched’s team has identified a novel oncogenic pathway, termed NVT, which is particularly active in resistant forms of hepatoblastoma. While immunotherapy (IT) has proven effective in stimulating the immune system to treat certain cancers, its efficacy is limited: some cancers fail to respond or develop resistance, often due to the reactivation of the NVT pathway.
To address these challenges, the INCa-supported project aims to develop innovative, non-viral, bioinspired, and biodegradable nanoparticles that can specifically target cancer cells. These nanoparticles will deliver therapeutic tools designed to neutralize the NVT pathway while simultaneously inhibiting signals that suppress the activity of anti-cancer immune cells.

Collaboration and expertise
Thanks to this collaboration, the team proposes to develop therapeutic nanoparticles in the form of nucleolipid nanovehicles, an innovation based on the expertise of Valérie Desvergnes. Furthermore, the approach will use antisense oligonucleotide (ASO) technology, short strands of DNA or RNA designed to inhibit the translation of target proteins. The development of this technology will be supported by the expertise of Virginie Baylot in ASO and immunotherapy, who will soon join Aksam Merched’s team. The project is strengthened thanks to the expertise of Christophe Grosset in the HB and the involvement of Pauline Trousselier and Morgan Wloch who are already part of another collaborative program between Mircade and BANCO.
Perspectives
This innovative approach holds the promise of surpassing current immunotherapies by delivering greater effectiveness while minimizing side effects and reducing the risk of resistance. Furthermore, the incorporation of appropriate preventive measures is expected to enhance its clinical applicability and impact.
The launch of this project was made possible through the support of emergence initiative of the Cancéropôle du Grand Sud-Ouest, the special support of the associations Les Récoltes de l’Espoir and Cassandra contre les Cancers Pédiatriques and the hard work of Hala Fatrouni and Hadi Najem, two PhD students supervised by Aksam Merched. This partnership between biologists and chemists was facilitated thanks to the RIE (Exploratory Interdisciplinary Research) program at the University of Bordeaux, which selected the NoViTher collaborative project between Valérie Desvergnes and Christophe Grosset in 2023.
