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

Luis Álvarez-Vallina, Rosa Yañez, Bélen Blanco, Magdalena Gil, Stephen J. Russell

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

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 under 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.

Original languageEnglish (US)
Pages (from-to)526-529
Number of pages4
JournalCancer Gene Therapy
Volume7
Issue number4
DOIs
StatePublished - 2000

Keywords

  • Chimeric T-cell receptors
  • Engineered T cells
  • Tetracycline-suppressible promoter

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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