Receptor for interleukin 13 is a marker and therapeutic target for human high-grade gliomas

Clin Cancer Res. 1999 May;5(5):985-90.

Abstract

Glioblastoma multiforme (GBM) is an incurable brain tumor. Due to the striking heterogeneity that characterizes GBM, there is no known tumor-specific antigen or receptor that is expressed by a majority of GBM patients. We found that virtually all studied human GBM specimens (23 samples) abundantly expressed a receptor for interleukin (IL)-13 in situ, whereas normal human brain had few, if any, IL-13-binding sites. The GBM-associated IL-13 receptor was both quantitatively and qualitatively different from and, thus, more restrictive than the shared signaling receptor of normal tissue: it was IL-4 independent. The receptor for IL-13 was overexpressed by a majority of cancer cells in situ. Furthermore, cytotoxins targeted to this more restrictive IL-13R produced cures in animals bearing xenografts of human high-grade gliomas. Thus, unexpectedly, the receptor for an immune regulatory cytokine may be a long sought marker and, concomitantly, a unique imaging site and therapeutic target for GBM, the most malignant and the most heterogeneous of brain tumors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Animals
  • Biomarkers, Tumor / analysis*
  • Brain Chemistry
  • Brain Neoplasms / chemistry*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma / chemistry*
  • Glioblastoma / genetics
  • Glioblastoma / pathology
  • Glioblastoma / therapy
  • Humans
  • Immunotoxins / therapeutic use
  • Interleukin-13 / metabolism
  • Interleukin-13 Receptor alpha1 Subunit
  • Interleukin-4 / pharmacology
  • Male
  • Mice
  • Mice, Nude
  • Mice, SCID
  • Middle Aged
  • Neoplasm Proteins / analysis*
  • Neoplasm Transplantation
  • Nerve Tissue Proteins / analysis*
  • Receptors, Interleukin / analysis*
  • Receptors, Interleukin-13
  • Recombinant Proteins / metabolism
  • Transplantation, Heterologous

Substances

  • Biomarkers, Tumor
  • IL13RA1 protein, human
  • Il13ra1 protein, mouse
  • Immunotoxins
  • Interleukin-13
  • Interleukin-13 Receptor alpha1 Subunit
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-13
  • Recombinant Proteins
  • Interleukin-4