HUMAN NEUROLOGICAL CANCER-CELLS EXPRESS INTERLEUKIN-4 (IL-4) RECEPTORS WHICH ARE TARGETS FOR THE TOXIC EFFECTS OF IL4-PSEUDOMONAS EXOTOXIN CHIMERIC PROTEIN

Glioblastoma, glioma or neuroblastoma cells were examined for the expr ession of IL-4 receptors (IL-4R) by now cytometric analysis and I-125- IL-4 binding. These cancer cell lines expressed IL-4R which were of hi gh affinity (K-D = 700 x 10(-12) M) on glioblastoma cells. To investig ate the function of these receptors and to target potent cytotoxic ant itumor agents to human neurological cancers, we utilized IL4-PE4E, whi ch is composed of IL-4 and mutant Pseudomonas exotoxin (IL4-PE4E). Thi s chimeric molecule was cytotoxic toward human glioblastoma, neuroblas toma and glioma tumor cells in a dose-dependent manner. The cytotoxici ty 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 te sted. IL2-PE4E and IL6-PE4E were not cytotoxic, nor was an IL4-PE4E mu tant lacking ADP-ribosylating activity, indicating the IL4-PE4E-mediat ed cytotoxicity of the brain tumor cells required both IL-4R binding a nd enzymatic toxin activity. These data indicate that human neurologic al cancer cells express IL-4R which are targets for the cytotoxic effe cts of IL4-toxin. In addition, our data also suggest that IL4-PE4E sho uld be studied further as a potential treatment for human neurological cancers. (C) 1994 Wiley-Liss, Inc.