Project

Chimeric antigen receptor (CAR) T cells have shown promising success to treat B cell malignancies but many solid tumors do not respond to these treatments.
To address this issue, we will develop a mice model of solid tumor for anti-CD19 CAR T cell therapy that we could compare with well establish models of B cell malignancies, pro-B acute leukemia and Burkitt lymphoma. The solid tumor model will be based on several tumor cell lines both expressing FRET-based reporter for apoptosis, the DEVD probe, and CD19 (MC38-CD19-DEVD and B16-CD19-DEVD). We will inject ectopically these tumors in conditioned mice then we will treat them with anti-CD19 CAR T. We will perform intravital biphotonic imaging directly in the solid tumor or in the bone marrow to compare the CAR T cells dynamics (speed, trajectories) and killing capacities: contacts between CAR T cells and tumor (time and number of contacts per CAR T cells), apoptotic events after direct contacts. We will also analyze tumor CAR T cell infiltration using flow cytometry. Finally, we will perform bulk RNA seq to investigate how CAR T cells modulates tumor cells’ phenotype. As a conclusion, this project’s aim is to improve current knowledge about CAR T cells in solid tumors.