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

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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Cepero E,Hnatyszyn HJ,Kraus G,Lichtenheld MG

doi

10.1006/bbrc.1998.8889

subject

Has Abstract

pub_date

1998-06-29 00:00:00

pages

838-43

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(98)98889-1

journal_volume

247

pub_type

杂志文章

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