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Human neurological cancer cells express interleukin‐4 (IL‐4) receptors which are targets for the toxic effects of IL4‐ pseudomonas exotoxin chimeric protein
Author(s) -
Puri Raj K.,
Leland Pamela,
Kreitman Robert J.,
Pastan Ira
Publication year - 1994
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910580421
Subject(s) - pseudomonas exotoxin , cytotoxic t cell , exotoxin , interleukin 4 , biology , cytotoxicity , glioma , cancer research , receptor , neuroblastoma , interleukin 2 , interleukin 4 receptor , interleukin 12 , cancer cell , interleukin , microbiology and biotechnology , immunology , cell culture , cancer , cytokine , toxin , biochemistry , in vitro , genetics
Glioblastoma, glioma or neuroblastoma cells were examined for the expression of IL‐4 receptors (IL‐4R) by flow cytometric analysis and 125 I‐IL‐4 binding. These cancer cell lines expressed IL‐4R which were of high affinity (K D = 700 × 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.