Potent inhibition of CTLA-4 expression by an anti-CTLA-4 ribozyme

Enrique Cepero, H. James Hnatyszyn, Günter Kraus, Mathias G. Lichtenheld

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Blockading the negative-regulatory CTLA-4 receptor has emerged as a powerful strategy with clinical potential to enhance T-cell responses. Some experimental tumors, for example, are rejected when anti-CTLA-4 antibodies are administered in vivo. The concise target cells and downstream events, however, remain to be defined. The development of gene transfer reagents that inhibit CTLA-4 may facilitate such investigations and may expand the therapeutic range. This communication describes an anti-CTLA-4 hairpin ribozyme that specifically abrogates CTLA-4 expression after gene transfer into a murine T-cell model. The analysis of multiple and independently derived clones and bulk cultures showed that CTLA-4 induction was inhibited > 90% at the RNA level and that it was undetectable at the protein level, with and without selective pressure. This potent inhibition required the catalytic function of the ribozyme. The anti-CTLA-4 ribozyme may be an alternative tool with which to continue the functional and therapeutical exploration of CTLA-4.

Original languageEnglish (US)
Pages (from-to)838-843
Number of pages6
JournalBiochemical and biophysical research communications
Volume247
Issue number3
DOIs
StatePublished - Jun 29 1998

Keywords

  • Gene transfer
  • Immunotherapy
  • T-cell activation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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