Cancer Gene Therapy Utilizing Interleukin-13 Receptor α2 Chain

Title: Cancer Gene Therapy Utilizing Interleukin-13 Receptor α2 Chain

Volume: 5 Issue: 2

Author(s): Koji Kawakami

Affiliation:

Keywords: cancer gene therapy, interleukin-13, cytokine receptor, immunotherapy, tumor vaccine, immunotoxin

Abstract: Cancer cells are known to express cell surface molecules such as specific antigens or cytokine receptors, e.g., EGFR, Fas / CD95, gp100, HER-2 / neu, IL-13Rα2, and MAGE. Among them, interleukin-13 receptor (IL-13R) a2 chain is expressed on certain types of cancer cells including glioblastoma, AIDS Kaposis sarcoma, and head and neck cancer. This protein is one of the receptor components for IL-13, a Th2 cell-derived pleiotropic immune regulatory cytokine. IL- 13Rα2 chain on these cancer cells can be targeted with a receptor-directed cytotoxin termed IL13-PE to induce specific cancer cell killing, however, this molecule does not mediate cytotoxicity to cells that do not express or express low levels of IL-13Rα2. In order to achieve a broad therapeutic window for IL13-PE, plasmid-mediated gene transfer of IL-13Rα2 in cancer cells was employed in vitro and in vivo. Cancer cells transfected with IL-13Rα2 demonstrated increased binding to IL-13 and sensitivity to IL13-PE in vitro. In vivo intratumoral gene transfer of IL-13Rα2 profoundly enhanced the antitumor activity of IL13-PE, providing complete elimination of established tumor in some xenografts. In this review article, current findings from IL-13Rα2 gene transfer in a variety of human cancer models in nude mice are summarized. In addition, safety issues and possible future directions utilizing this therapeutic approach are discussed.

Cite this article as:

Kawakami Koji, Cancer Gene Therapy Utilizing Interleukin-13 Receptor α2 Chain, Current Gene Therapy 2005; 5 (2) . https://dx.doi.org/10.2174/1566523053544227