Timely controlled T-cell receptor expression against a leukemia-associated antigen for the co-transplantation of MHC-mismatched T-cell precursors into hematopoietic stem cell reci…

Adoptive transfer (AT) of TCR-gene modified T cells has been associated with several drawbacks: 1) In vitro stimulation required for TCR-gene transduction can profoundly impact its vivo function after AT; 2) TCR-chain mispairing can cause potentially life threatening autoreactivity; and 3) HLA-matched T cell donors are required. Here, we report the in vitro generation of precursor T-cells, with a phenotype similar to thymic double negative (DN)-2 cells. They were generated from murine hematopoietic stem cells that were genetically engineered to conditionally express a TCR against a surrogate tumor-associated ant…