In vivo reprogramming of antitumor immunity

Our team is developing strategies to directly reprogram immune cells in vivo in order to enhance their ability to recognize and eliminate tumor cells. This approach offers an alternative to cell therapy strategies that rely on complex ex vivo manipulation. At the intersection of basic immunology, targeted delivery technologies, and translational oncology, we seek to develop new immunotherapies that act directly within the tumor microenvironment. To develop and evaluate these strategies, we combine in vivo, ex vivo, and in vitro models with state-of-the-art approaches in imaging, transcriptomics, proteomics, and multiparametric cytometry. A major component involves the targeted delivery of therapeutic molecules, particularly in the form of mRNA encapsulated in lipid nanoparticles (LNPs). The goal is, in particular, to overcome two major obstacles in solid tumor immunotherapies: insufficient infiltration of effector cells and the limited availability of specific tumor targets. The team’s work draws on internationally recognized expertise in the biology of natural killer (NK) cells and their therapeutic application in oncology. In particular, they have helped unravel the heterogeneity of NK cells and the mechanisms regulating their antitumor activity, as well as develop strategies for mobilizing these cytotoxic cells. More recently, the team has expanded this expertise to the identification of new tumor antigens derived from unconventional regions of the genome.

• Research Area 1 – In vivo programming of immune cells by engaging molecules. We seek to mobilize the antitumor functions of cytotoxic cells present within the tumor using a new generation of molecules capable of engaging and activating them locally.

• Research Area 2 – In vivo reprogramming of the tumor microenvironment. We aim to promote the recruitment and infiltration of cytotoxic cells into solid tumors by locally modulating signals from the tumor microenvironment, particularly chemokines.

• Research Area 3 – Discovery of new tumor antigens derived from the “dark genome.” A large portion of the human genome does not correspond to the traditionally annotated protein-coding regions, yet remains transcriptionally active and dysregulated in cancers. Our goal is to identify tumor antigens within these regions—whether shared across tumors or specific to certain tumors—and to exploit them as new targets for immunotherapy.