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 |
|---|---|
| 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 |
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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 journal › Article
}
TY - JOUR
T1 - Potent inhibition of CTLA-4 expression by an anti-CTLA-4 ribozyme
AU - Cepero, Enrique
AU - Hnatyszyn, H. James
AU - Kraus, Günter
AU - Lichtenheld, Mathias G
PY - 1998/6/29
Y1 - 1998/6/29
N2 - 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.
AB - 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.
KW - Gene transfer
KW - Immunotherapy
KW - T-cell activation
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U2 - 10.1006/bbrc.1998.8889
DO - 10.1006/bbrc.1998.8889
M3 - Article
VL - 247
SP - 838
EP - 843
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -