Description

Development of novel anti-tumor immunotherapies using optimized experimental mouse model

P. De La Rochère¹, M. Dubois^1,3, F. Nemati^1,3, M. Rathaux^1,3, N. Nunez¹, S. Viel¹, D. Meseure², A. Salomon², C. Sedlik¹, D. Decaudin³, E. Piaggio¹

¹ Institut Curie, PSL Research University, INSERM U932, SIRIC, Translational Immunotherapy Team ² Institut Curie, PSL Research University, Département de biologie des tumeurs, ³Institut Curie, PSL Research University, INSERM U932, Laboratoire d’investigation pré-clinique; Paris, F-75005 France

Cancer immunotherapy is switching the target of cancer treatment from the tumor to the immune system. The blockade of immune checkpoints (molecules that modulate antigen-specific T cell responses) with antibodies (Abs) anti-CTLA-4, anti-PD1 and anti-PD-L1, has given impressive clinical results. Thus, today many immunotherapies based on anti-checkpoint Abs as monodrugs or as combinations are awaiting to be tested in experimental models before going into the clinic. However, only a few non-satisfactory animal models are available. Thus, our objective is to optimize the existing mouse models and to create new "humanized" mouse models to facilitate the transfer of novel immunotherapies to the patients. For that we will assess the therapeutic potential of chosen therapies in mouse models consisting of immunodeficient NSG mice transplanted with human tumors (cell lines or patient-derived xenografts (PDX)) and adoptively transferred with human PBMCs or with immune cells coming from human tumor-draining lymph nodes. Our preliminary results sustain the feasibility of our model and we are actually testing anti-checkpoint Abs alone or combined with other therapies developed by our team.