In vivo manipulation of interleukin-2 expression by a retroviral tetracycline (tet)-regulated system
- We have used the tetracycline (tet)-regulated system as described previously to evaluate the applicability of controlled gene expression in cancer gene therapy. As a model gene, we used the human interleukin-2 (IL-2) gene, which has been placed under the transcriptional control of the tetO/promoter. Human melanoma cells were transduced by two modified retroviral tet vectors containing the transactivator regulatory unit and the IL-2 gene driven by the tetO/promoter, respectively. In the absence of tet, IL-2 expression in the target cells was stable over several months. IL-2 production was in the range of 40 U/106 cells/24 hours. A fine tuning of IL-2 expression could be achieved by culturing the transduced cells with increasing doses of tet, whereby a concentration of 500 ng/mL tet in the culture medium abrogated IL-2 expression. Most importantly for clinical application, IL-2 expression by the transduced melanoma cells could also be regulated in vivo. When nu/nu mice were inoculated with the transduced tumor cells, they failed to develop tumors. Instead, the inhibition of IL-2 expression in the transduced tumor cells by oral administration of tet led to subcutaneous tumor growth; this growth rate was comparable with the growth rate of subcutaneously inoculated untransduced parental cells. The finding demonstrates the applicability of the tet-regulated system in cancer gene therapy.
Author: | Claudia Pitzer, Katharina SchindowskiORCiDGND, Sigmund Pomer, Thomas Wirth, Margot Zöller |
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URN: | urn:nbn:de:hebis:30-34423 |
DOI: | https://doi.org/10.1038/sj.cgt.7700021 |
ISSN: | 1476-5500 |
ISSN: | 0929-1903 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/10195880 |
Parent Title (English): | Cancer gene therapy |
Publisher: | Nature Publ. Group |
Place of publication: | New York, NY |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2006/12/05 |
Year of first Publication: | 1999 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2006/12/05 |
Tag: | gene therapy; interleukin-2 gene; tetracycline; tumor vaccines |
Volume: | 6 |
Issue: | 2 |
Page Number: | 8 |
First Page: | 139 |
Last Page: | 146 |
HeBIS-PPN: | 288692403 |
Institutes: | Biochemie, Chemie und Pharmazie / Pharmazie |
Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
Sammlungen: | Sammlung Biologie / Sondersammelgebiets-Volltexte |
Licence (German): | Deutsches Urheberrecht |