Johannes Huppa, PhD, Medical University of Vienna, Vienna, Austria, outlines the differences between T-cells and CAR T-cells and how they play a crucial part in the reduced sensitivity of CAR T-cells. Dr Huppa highlights how the reduced sensitivity is related to relapse due to antigen downregulation, as the CAR T-cells are not capable of transducing a binding event into a signaling response as well as T-cells. This interview took place at the 2nd European CAR T-Cell Meeting in Sitges, Spain.