biostudies-literatureHoseini SSNHLBI NIH HHSNCI NIH HHS1530-42https://www.ebi.ac.uk/biostudies/studies/S-EPMC4607259biostudies-literatureUnknown29(7)Co-transplantation of hematopoietic stem cells with those engineered to express leukemia-reactive T-cell receptors (TCRs) and differentiated ex vivo into precursor T cells (preTs) may reduce the risk of leukemia relapse. As expression of potentially self-(leukemia-) reactive TCRs will lead to negative selection or provoke autoimmunity upon thymic maturation, we investigated a novel concept whereby TCR expression set under the control of an inducible promoter would allow timely controlled TCR expression. After in vivo maturation and gene induction, preTs developed potent anti-leukemia effects. Engineered preTs provided protection even after repeated leukemia challenges by giving rise to effector and central memory cells. Importantly, adoptive transfer of TCR-transduced allogeneic preTs mediLeukemiaInducible T-cell receptor expression in precursor T cells for leukemia control.PMC4607259P01 CA065493R01 CA72669R01 CA072669R01 HL056067Heinz NHerbst JVignali DAWedekind DBaumann RBlazar BRvan den Brink MRSchambach ASchiedlmeier BHapke MHoseini SSSauer MGfalseInducible T-cell receptor expression in precursor T cells for leukemia control.Co-transplantation of hematopoietic stem cells with those engineered to express leukemia-reactive T-cell receptors (TCRs) and differentiated ex vivo into precursor T cells (preTs) may reduce the risk of leukemia relapse. As expression of potentially self-(leukemia-) reactive TCRs will lead to negative selection or provoke autoimmunity upon thymic maturation, we investigated a novel concept whereby TCR expression set under the control of an inducible promoter would allow timely controlled TCR expression. After in vivo maturation and gene induction, preTs developed potent anti-leukemia effects. Engineered preTs provided protection even after repeated leukemia challenges by giving rise to effector and central memory cells. Importantly, adoptive transfer of TCR-transduced allogeneic preTs medi2015-01-01T00:00:00Z2015 Jul2025-04-04T01:29:09.685Z2019-03-27T02:00:08ZS-EPMC46072592565273910.1038/leu.2015.20