Analysis of interleukin-13 receptor α2 expression in human pediatric brain tumors

Fujita Health University, Nagoya, Aichi, Japan
Cancer (Impact Factor: 4.89). 09/2004; 101(5):1036-42. DOI: 10.1002/cncr.20470
Source: PubMed


Compared with normal brain tissue cells, human malignant glioma cells express higher levels of interleukin-13 receptor (IL-13R). However, whether this receptor is expressed in situ has not been carefully examined. With IL-13R-targeted cytotoxin (IL13-PE38QQR, comprising IL-13 and a mutated form of Pseudomonas exotoxin [PE]) being tested in three Phase I/II clinical trials for the treatment of adult human glioma, and with pediatric studies being planned, the authors set out to analyze pediatric brain tumor tissue specimens for the expression of IL-13R.
Using in situ hybridization and immunohistochemical staining, the authors examined 58 pediatric brain tumor specimens for expression of the predominant IL-13 binding and internalizing protein (IL-13Ralpha2) chain at the mRNA and protein levels.
Overall, approximately 83% of pediatric brain tumor samples expressed IL-13Ralpha2. One hundred percent (11 of 11) high-grade astrocytoma, 79% (26 of 33) low-grade astrocytoma, 67% (4 of 6) medulloblastoma, and 67% (2 of 3) ependymoma samples were positive for IL-13Ralpha2. Among IL-13Ralpha2-positive samples, 88% (42 of 48 samples) had positive expression in > or = 50% of all tumor fields. The results obtained using both assays were consistent with each other.
The current study established that pediatric brain tumor specimens expressed the IL-13Ralpha2 chain. Because the IL-13Ralpha2 chain is a major binding component of the IL-13R complex, these results suggest that the targeting of IL-13R may represent a useful approach for the treatment of pediatric brain tumors.

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Available from: Satoru Takahashi, Oct 09, 2014
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    • "Abundance of IL13Rα2 overexpression in GBM is a well-documented fact [13, 14, 41, 63–65]. IL13Rα2 is expressed in approximately 58% of adult and 83% of the pediatric brain tumors as well as on glioma-initiating cells [13, 41, 65]. "
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    ABSTRACT: Glioblastoma (GBM) is the most lethal primary brain tumor, and despite several refinements in its multimodal management, generally has very poor prognosis. Targeted immunotherapy is an emerging field of research that shows great promise in the treatment of GBM. One of the most extensively studied targets is the interleukin-13 receptor alpha chain variant 2 (IL13Rα2). Its selective expression on GBM, discovered almost two decades ago, has been a target for therapy ever since. Immunotherapeutic strategies have been developed targeting IL13Rα2, including monoclonal antibodies as well as cell-based strategies such as IL13Rα2-pulsed dendritic cells and IL13Rα2-targeted chimeric antigen receptor-expressing T cells. Advanced therapeutic development has led to the completion of several clinical trials with promising outcomes. In this review, we will discuss the recent advances in the IL13Rα2-targeted immunotherapy and evaluate the most promising strategy for targeted GBM immunotherapy.
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    • "One attractive immunotherapy target is IL13Rα2, a 42-kDa monomeric high affinity IL-13 receptor distinct from the more ubiquitously expressed IL-13Rα1/IL-4Rα receptor complex [3]. IL13Rα2 is expressed by a high percentage of gliomas, but not at significant levels on normal brain tissue [4]–[7], and in IL13Rα2-expressing tumors has been identified on both stem-like malignant cells and their more differentiated counterparts [8]. Targeting IL13Rα2 is currently the focus of ongoing clinical development for the treatment of brain tumors [8]–[12]. "
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    • "IL-13Rα2 is overexpressed on certain types of human tumor tissues [15-22]. We now provide evidence that IL-13Rα2 is highly expressed in a variety of murine tumor cell lines (Additional file 1, Figure S1). "
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