Human neurological cancer cells express interleukin-4 (IL-4) receptors which are targets for the toxic effects of IL4-Pseudomonas exotoxin chimeric protein

Int J Cancer. 1994 Aug 15;58(4):574-81. doi: 10.1002/ijc.2910580421.

Abstract

Glioblastoma, glioma or neuroblastoma cells were examined for the expression of IL-4 receptors (IL-4R) by flow cytometric analysis and 125I-IL-4 binding. These cancer cell lines expressed IL-4R which were of high affinity (KD = 700 x 10(-12) M) on glioblastoma cells. To investigate the function of these receptors and to target potent cytotoxic antitumor agents to human neurological cancers, we utilized IL4-PE4E, which is composed of IL-4 and mutant Pseudomonas exotoxin (IL4-PE4E). This chimeric molecule was cytotoxic toward human glioblastoma, neuroblastoma and glioma tumor cells in a dose-dependent manner. The cytotoxicity of IL4-PE4E was specific, since it was neutralized by excess IL-4, and by an anti-IL-4 monoclonal antibody in all types of brain tumor tested. IL2-PE4E and IL6-PE4E were not cytotoxic, nor was an IL4-PE4E mutant lacking ADP-ribosylating activity, indicating the IL4-PE4E-mediated cytotoxicity of the brain tumor cells required both IL-4R binding and enzymatic toxin activity. These data indicate that human neurological cancer cells express IL-4R which are targets for the cytotoxic effects of IL4-toxin. In addition, our data also suggest that IL4-PE4E should be studied further as a potential treatment for human neurological cancers.

MeSH terms

  • ADP Ribose Transferases*
  • Bacterial Toxins / pharmacology*
  • Brain Neoplasms / metabolism*
  • Exotoxins
  • Flow Cytometry
  • Glioblastoma / metabolism
  • Glioma / metabolism
  • Humans
  • Neuroblastoma / metabolism
  • Pseudomonas aeruginosa
  • Receptors, Interleukin-4
  • Receptors, Mitogen / metabolism*
  • Recombinant Proteins / pharmacology*
  • Tumor Cells, Cultured
  • Virulence Factors*

Substances

  • Bacterial Toxins
  • Exotoxins
  • Receptors, Interleukin-4
  • Receptors, Mitogen
  • Recombinant Proteins
  • Virulence Factors
  • ADP Ribose Transferases
  • toxA protein, Pseudomonas aeruginosa