Pharmacologic suppression of target cell recognition by engineered T cells expressing chimeric T-cell receptors.
Adoptive therapy with autologous T cells expressing chimeric T-cell receptors (chTCRs) is of potential interest for the treatment of malignancy. To limit possible T-cell-mediated damage to normal tissues that weakly express the targeted tumor antigen (Ag), we have tested a strategy for the suppression of target cell recognition by engineered T cells. Jurkat T cells were transduced with an anti-hapten chTCR tinder the control of a tetracycline-suppressible promoter and were shown to respond to Ag-positive (hapten-coated) but not to Ag-negative target cells. The engineered T cells were then reacted with hapten-coated target cells at different effector to target cell ratios before and after exposure to tetracycline. When the engineered T cells were treated with tetracycline, expression of the chTCR was greatly decreased and recognition of the hapten-coated target cells was completely suppressed. Tetracycline-mediated suppression of target cell recognition by engineered T cells may be a useful strategy to limit the toxicity of the approach to cancer gene therapy.
Alvarez-Vallina
L
L
Department of Immunology, Hospital Universitario Clínica Puerta de Hierro, Madrid, Spain. Luis.Alvarez@inmu.cph.es
Yañez
R
R
Blanco
B
B
Gil
M
M
Russell
S J
SJ
D005434:Flow Cytometry; D006241:Haptens / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D009592:Nitrohydroxyiodophenylacetate / Q000494:pharmacology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics* / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013752:Tetracycline / Q000494:pharmacology; D014162:Transfection
D006241:Haptens; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D009592:Nitrohydroxyiodophenylacetate; D013752:Tetracycline