ENHANCEMENT OF EPIDERMAL GROWTH-FACTOR RECEPTOR EXPRESSION ON GLIOMA-CELLS BY RECOMBINANT TUMOR-NECROSIS-FACTOR-ALPHA

Recombinant tumor necrosis factor-alpha (rTNF-alpha; optimal dose 1000 U/ml) significantly increased the density of epidermal growth factor receptor (EGF-R) in three of four glioma cell lines in culture as determined by binding analysis of anti-EGF-R monoclonal antibody (mAb) 425. Since enhancement of EGF-R expression by rTNF-alpha was inhibited when cells were treated with the protein synthesis inhibitor cycloheximide, the effects of rTNF-alpha may be protein-synthesis-dependent. The dose of rTNF-alpha that was optimal for up-regulation of EGF-R on glioma cells did not inhibit the growth of these cells. I-125-labeled mAb 425 lysed glioma cells in culture following its internalization into the cells. After glioma cells had been treated with rTNF-alpha, the growth-inhibitory effects of the mAb were significantly enhanced, probably a reflection of the increase in EGF-R density on the tumor cell surfaces. The rTNF-alpha effects were specific to the EGF-R and did not affect unrelated glioma-associated antigens. In our previous clinical trials, I-125-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with I-125-labeled mAb 425 and rTNF-alpha.