CAR T cells therapy complications and therapeutic potential of endothelial cells protecting agents

Chimeric Antigen Receptor T-cells (CAR-Ts) recently revolutionized the treatment of hematologic malignancies, especially relapsed/refractory lymphomas, myeloma and leukaemias. However, this therapy is frequently associated to unwanted side effects which are still troublesome and can be lethal in some cases. The most frequent toxic effects are the Cytokine Release Syndrome (CRS) and the Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS). By understanding the complex interaction between CAR-Ts, Target cells, Host Immune response, and the cytokines released, it is possible to develop promising prevention and treatment strategies, with the aim of reducing the impact of and developing safer treatments for these syndromes. In this thesis we will discuss about CAR prevention strategies that can be taken in consideration while designing CAR themselves by systematically analysing their different components, how they interact with each other and influence efficacy, persistency, prolificacy, and toxicity of CAR-Ts. We then discuss about one potential treatment option for both CRS and ICANS which targets endothelial cells activation, a main feature for both complications.