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 Citations (Scopus)

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
Pages (from-to)838-843
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume247
Issue number3
DOIs
StatePublished - Jun 29 1998

Fingerprint

Gene transfer
Catalytic RNA
T-cells
T-Lymphocytes
Tumors
Clone Cells
RNA
Gene Expression
Antibodies
Communication
Genes
Neoplasms
Proteins
Therapeutics
hairpin ribozyme

Keywords

  • Gene transfer
  • Immunotherapy
  • T-cell activation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Potent inhibition of CTLA-4 expression by an anti-CTLA-4 ribozyme. / Cepero, Enrique; Hnatyszyn, H. James; Kraus, Günter; Lichtenheld, Mathias G.

In: Biochemical and Biophysical Research Communications, Vol. 247, No. 3, 29.06.1998, p. 838-843.

Research output: Contribution to journalArticle

Cepero, Enrique ; Hnatyszyn, H. James ; Kraus, Günter ; Lichtenheld, Mathias G. / Potent inhibition of CTLA-4 expression by an anti-CTLA-4 ribozyme. In: Biochemical and Biophysical Research Communications. 1998 ; Vol. 247, No. 3. pp. 838-843.
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