Overcome immunosuppression in the tumor microenvironment for effective CAR T cell targeting of pediatric solid tumors

CAR T cell therapies have high potential for the treatment of cancer, but activity in solid tumors remains limited. Evidence is accumulating that tumor-associated macrophages with immunosuppressive function are a key barrier for CAR T cells in pediatric solid tumors. We hypothesize that agents that eliminate or reprogram myeloid cell components can reshape the tumor microenvironment and enable effective infiltration and functional activity of CAR T cells. This project aims to identify the most adequate agents from panels of selected candidates and screens of pharmacological agents and epigenetic and small/molecule modifiers in 3D models of tumor cells, macrophages and both B7H3 and GD2-specific CAR T cells.

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Stijn Kleerebezem