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Cancer Gene Ther. 2001 Nov;8(11):861-8.

Gene transfer of interleukin 13 receptor alpha2 chain dramatically enhances the antitumor effect of IL-13 receptor-targeted cytotoxin in human prostate cancer xenografts.

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1
Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.

Abstract

IL-13Ralpha2 chain, the primary interleukin-13 (IL-13) binding protein, plays an important role in IL-13 binding and internalization. Based on these findings, in our previous study we transiently transfected four cancer cell lines that do not express IL-13Ralpha2 chain and demonstrated that these cells acquired increased sensitivity to IL-13 receptor-targeted recombinant cytotoxin, IL13-PE38QQR, which is composed of IL-13 and a mutated form of a Pseudomonas exotoxin. Although some prostate cancer cell lines express functional IL-13R, they are not highly sensitive to IL-13 cytotoxin. Here we investigated whether human prostate cancer and normal prostate epithelial cell lines express IL-13Ralpha2 chain and whether they can be sensitized to the cytotoxic effect of IL-13 cytotoxin after transient or stable gene transfer of IL-13Ralpha2 chain. Gene transfer of IL-13Ralpha2 chain improved binding activity of IL-13 and sensitivity to IL-13 cytotoxin in vitro. In vivo experiments demonstrated that gene transfer of IL-13Ralpha2 chain dramatically enhanced the antitumor activity of IL-13 cytotoxin in human prostate cancer xenograft models. These results suggest that IL-13R-targeted cytotoxin therapy of prostate cancer may be dramatically enhanced by gene transfer of IL-13Ralpha2 chain and this strategy, the combination of gene therapy and cytotoxin therapy, may be utilized in the treatment of localized prostate cancer.

PMID:
11773976
DOI:
10.1038/sj.cgt.7700373
[Indexed for MEDLINE]
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