Send to

Choose Destination
J Immunother. 2005 May-Jun;28(3):193-202.

Evidence that IL-13R alpha2 chain in human glioma cells is responsible for the antitumor activity mediated by receptor-directed cytotoxin therapy.

Author information

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.


The interleukin-13 receptor alpha2 (IL-13R alpha2) chain is a primary IL-13 binding and internalization component of the IL-13R system. Previous studies have shown that human brain tumors, including glioblastoma multiforme (GBM), overexpress IL-13R alpha2 chain, while normal brain cells do not express this protein or express very low levels of it. To target IL-13R on brain tumor cells, the authors have developed an IL-13R-directed cytotoxin termed IL13-PE38QQR to induce specific cancer cell killing. To investigate the role of IL-13R alpha2 chain in GBM, cells were treated with antisense oligonucleotide or siRNA to IL-13R alpha2 chain, and cellular IL-13 binding and sensitivity to IL-13 cytotoxin were assessed. IL-13R alpha2 gene interference in GBM cells showed decreased ligand binding, and consequently IL-13 cytotoxin exhibited less cytotoxicity to these cells. The authors next evaluated the antitumor activity of IL-13 cytotoxin in native IL-13R-expressing tumors and after gene transfer of IL-13R alpha2 by injecting plasmid in U87MG tumors subcutaneously implanted in nude mice. These mice were then treated with IL-13 cytotoxin. Mean tumor size in mice receiving intraperitoneal or intratumoral IL-13 cytotoxin was significantly smaller in control tumors; however, tumor sizes were much smaller in IL-13R alpha2-transfected tumors. Furthermore, convection-enhanced delivery of IL-13R alpha2 cDNA in intracranially established U87MG glioma followed by IL-13 cytotoxin administration by the same route mediated tumor regression and prolonged survival of animals by 164% compared with control. These results indicate that IL-13R alpha2 chain in GBM cells is essential for IL-13 cytotoxin-induced cytotoxicity and that IL-13R alpha2 chain plays a critical biologic role in IL-13 cytotoxin-mediated therapy for GBM.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wolters Kluwer
Loading ...
Support Center