Pharmacologic suppression of target cell recognition by engineered T cellsexpressing chimeric T-cell receptors

Adoptive therapy with autologous T cells expressing chimeric T-cell recepto rs (chTCRs) is of potential interest for the treatment of malignancy. To li mit possible T-cell-mediated damage to normal tissues that weakly express t he targeted tumor antigen (Ag), we have tested a strategy for the suppressi on of target cell recognition by engineered T cells. Jurkat T cells were tr ansduced with an anti-hapten chTCR under the control of a tetracycline-supp ressible promoter and were shown to respond to Ag-positive (hapten-coated) but not to Ag-negative target cells. The engineered T cells were then react ed with hapten-coated target cells at different effector to target cell rat ios before and after exposure to tetracycline. When the engineered T cells were treated with tetracycline, expression of the chTCR was greatly decreas ed and recognition of the hapten-coated target cells was completely suppres sed. Tetracycline-mediated suppression of target cell recognition by engine ered T cells may be a useful strategy to limit the toxicity of the approach to cancer gene therapy.