Project 456857

Rhabdomyosarcoma (RMS) is the most common soft tissue cancer in childhood. Although progress in treatments have led to a remission rate of approximatively 60% of all pediatric cases, the prognosis of patients with high-risk RMS is still very poor. Therefore, there is a need for new and efficient immunotherapy in this disease. The strategy of Chimeric antibody receptor (CAR)-T cells has given lots of hope for cancer immunotherapy. In this strategy, the T cells, which are white cells (leukocytes) that belong to the immune system, are engineered to express at their surface a molecule (CAR) that recognize tumor cells and induce their killing by the T cells. Although this strategy has proven efficient in some forms of leukemia, it does not work in solid cancer such as RMS. Here, we propose to use two alternative strategies using CAR for RMS. In the first one, we will use NK cells instead of T cells, to develop CAR-NK cells. Natural Killer (NK) cells are also leukocytes that belong to the immune system and they have an intrinsic ability to recognize and kill tumor cells. Our lab has developed a tool that allow to engineer NK cells and we will test CAR-NK cells in RMS. Second, we will engineer hematopoietic stem cells (HSC), that are cells that give rise to all the leukocytes, including T and NK cells. We have designed and patented a tool that allow to engineer HSC and make them express the modification only in T and NK cells, and not in other leukocytes. Using CAR-HSC cells, we hope we will get CAR-T and CAR-NK cells that will work together against RMS, and that these CAR-T and CAR-NK cells will be produced continuously thereby preventing relapses. Together, this application will allow us to test 2 alternative strategies to CAR-T cells: the CAR-NK and the CAR-HSC. We will compare the pro and the cons of each one regarding efficacy, safety and feasibility.