CAR-engineered precursor T cells (preTs) for leukemia control after hematopoietic stem cell transplantation

Background: Co-transplanted CAR-engineered preTs are an attractive tool for preventing leukemia relapse. The impact on endogenous TCR expression and thereby thymic selection processes remains unclear. Methods: Murine haematopoietic stem cells were transduced with a lentiviral construct containing an inducible CAR against CD19 and then differentiated into preTs in vitro. Engineered preTs were characterised in vitro and in vivo. Results: High yields of engineered preTs can be generated in vitro expressing the murine CD19 CAR early during differentiation. The progeny of CAR-transduced preTs were functional after in…