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

Authors

  • Mariko Kawakami M.D., Ph.D.,

    1. Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
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  • Koji Kawakami M.D., Ph.D.,

    1. Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
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  • Satoru Takahashi M.D., Ph.D.,

    1. Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Aichi, Japan
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  • Masato Abe M.D.,

    1. Department of Surgical Pathology, Fujita Health University School of Medicine, Aichi, Japan
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  • Raj K. Puri M.D., Ph.D.

    Corresponding author
    1. Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland
    • Laboratory of Molecular Tumor Biology, Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, NIH Building 29B, Room 2NN10, HFM-735, Bethesda, MD 20892
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    • Fax: (301) 827-0449


  • This article is a U.S. Government work and, as such, is in the public domain in the United States of America.

  • The current study was conducted as part of a collaboration between the Food and Drug Administration and NeoPharm Inc. under a Cooperative Research and Development Agreement.

  • §

    The opinions expressed herein do not necessarily reflect the views of the Food and Drug Administration or the U.S. Government.

Abstract

BACKGROUND

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.

METHODS

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-13Rα2) chain at the mRNA and protein levels.

RESULTS

Overall, approximately 83% of pediatric brain tumor samples expressed IL-13Rα2. 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-13Rα2. Among IL-13Rα2–positive samples, 88% (42 of 48 samples) had positive expression in ≥ 50% of all tumor fields. The results obtained using both assays were consistent with each other.

CONCLUSIONS

The current study established that pediatric brain tumor specimens expressed the IL-13Rα2 chain. Because the IL-13Rα2 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. Cancer 2004. Published 2004 by the American Cancer Society.

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