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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| 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.
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| Authors | K Kawakami, S R Husain, R K Bright, R K Puri |
| Journal | Cancer gene therapy (Cancer Gene Ther) Vol. 8 Issue 11 Pg. 861-8 (Nov 2001) ISSN: 0929-1903 [Print] England |
| PMID | 11773976 (Publication Type: Journal Article) |
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