Chimeric Antigen Receptor (CAR) T cell therapy is a novel form of immunotherapy for the treatment of children with refractory or relapsed B-cell precursor acute lymphoblastic leukemia (BCP-ALL) that has dramatically increased the survival of patients. Although impressive clinical results have been obtained, treatment with CAR-T cell therapy is not effective in approximately half of the patients. This illustrates the medical need to better understand resistance mechanisms in order to improve therapy efficacy.
The bone marrow microenvironment of BCP-ALL plays a substantial role in the leukemic persistence and relapse. The expansion, function, and long-term persistence of CAR-T cells, associated with long-term disease-free survival, might be hampered by immunosuppressive characteristics within the leukemic bone marrow microenvironment (the leukemic niche). In this project, we will therefore study the effector function of CAR-T cells in relation to their cellular environment by modelling the dynamic interactions between CAR-T cells, leukemic blasts, and bone marrow components. We aim to characterize factors that influence the interaction and function of CAR-T cells using (3D) co-cultures and innovative imaging systems resembling an artificial bone marrow microenvironment.