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 (HCT…

Adoptive transfer (AT) of TCR-gene modified T cells has been associated with a couple of draw-backs. 1. Rigorous in vitro stimulation required for TCR-gene transduction can profoundly impact in 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 present a system designed to transduce stem cells with an anti-leukemic TCR-gen whose expression is regulated by a tetracycline-response-element (TRE). The new vector was primarily evaluated on murine T 58 cells and human Jurkat cells. The addition of doxycycline res…