TY  - JOUR
A1  - Pitzer, Claudia
A1  - Schindowski, Katharina
A1  - Pomer, Sigmund
A1  - Wirth, Thomas
A1  - Zöller, Margot
T1  - In vivo manipulation of interleukin-2 expression by a retroviral tetracycline (tet)-regulated system
T2  - Cancer gene therapy
N2  - 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.
KW  - tetracycline
KW  - interleukin-2 gene
KW  - gene therapy
KW  - tumor vaccines
Y1  - 2006
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/1917
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-34423
SN  - 1476-5500
SN  - 0929-1903
VL  - 6
IS  - 2
SP  - 139
EP  - 146
PB  - Nature Publ. Group
CY  - New York, NY
ER  -