Reprogramming cancer cells in dendritic cells to expand tumor-reactive infiltrating lymphocytes.

Description du projet

Expansion des lymphocytes d’infiltration réagissant à la tumeur

Les lymphocytes d’infiltration tumorale (TIL) sont des cellules immunitaires qui migrent dans les tumeurs et peuvent reconnaître et tuer les cellules cancéreuses. Leur utilisation dans le cadre de la thérapie cellulaire adoptive s’est avérée prometteuse, en particulier dans le cas du mélanome, pour lequel le traitement à base de TIL a récemment reçu l’approbation de la FDA. Cependant, l’expansion sélective des TIL qui ciblent réellement les cellules cancéreuses reste un défi majeur. Avec le soutien du programme Actions Marie Skłodowska-Curie, le projet ExpandTILs propose de reprogrammer des cellules tumorales dérivées de patients en cellules présentatrices d’antigènes afin d’augmenter de manière sélective les TIL réactifs à la tumeur. Les chercheurs apporteront la preuve de l’efficacité de cette nouvelle plateforme d’expansion des TIL, dans l’espoir d’offrir un traitement anticancéreux personnalisé et de transformer l’immunothérapie.

Objectif

Cancer affects 2.6 million people each year in the European Union, making it the second leading cause of death. Immunotherapies have revolutionized the treatment of cancer, seeking to re-arm immune cells against tumors. However, current immunotherapies are mostly inefficient in low immunogenic and solid tumors, which account for more than 80% of cancers in adults. A promising approach is to collect tumor infiltrating lymphocytes (TILs) from patient’s resected tumor tissue, and expand their function in vitro before reinjecting them to achieve antitumor immunity. This therapy is currently involved in many clinical trials and received a first FDA approval in 2024 for advanced melanoma treatment. Yet, a major challenge remains to amplify the diversity of tumor reactive TILs rather than the non-specific TILs.
The aim of the ExpandTILs project is to selectively amplify tumor-reactive TILs to enable personalized, targeted and effective tumor killing. I will use the unique system designed by the host team, reprogramming the patient tumor cells into antigen presenting dendritic cells, to amplify tumor reactive TILs. I will establish an optimized coculture protocol with reprogrammed cancer cells to expand antigen-specific TILs, then train in cutting-edge techniques to characterize and compare their antitumor efficacy to standard-of-care TILs. This interdisciplinary approach, combining cellular reprogramming with cancer immunology, will increase our knowledge about tumor-specific TILs responses and allow us to obtain the proof-of-concept for a tumor reactive TILs expansion platform. This should lead to the creation of a new company, allowing me to learn how to bring new technologies to clinic. Therefore, this fellowship will significantly contribute to my professional growth by allowing me to develop complementary skills in project management, leadership, communication, and entrepreneurship.