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 language | English (US) |
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Pages (from-to) | 838-843 |
Number of pages | 6 |
Journal | Biochemical and biophysical research communications |
Volume | 247 |
Issue number | 3 |
DOIs | |
State | Published - Jun 29 1998 |
Keywords
- Gene transfer
- Immunotherapy
- T-cell activation
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology