In vivo manipulation of interleukin-2 expression by a retroviral tetracycline (tet)-regulated system.

Abstract:

: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/10(6) 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.

journal_name

Cancer Gene Ther

journal_title

Cancer gene therapy

authors

Pitzer C,Schindowski K,Pomer S,Wirth T,Zöller M

doi

10.1038/sj.cgt.7700021

subject

Has Abstract

pub_date

1999-03-01 00:00:00

pages

139-46

issue

2

eissn

0929-1903

issn

1476-5500

journal_volume

6

pub_type

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