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. 1992 Nov;34(6):370–376. doi: 10.1007/BF01741746

Enhancement of epidermal growth factor receptor expression on glioma cells by recombinant tumor necrosis factor α

Koji Adachi 1, Paul Belser 1, Hans Bender 1, Derui Li 2, Ulrich Rodeck 1, Etty N Benveniste 3, David Woo 2, Wolff H Schmiegel 4, Dorothee Herlyn 1,✉
PMCID: PMC11038433  PMID: 1563013

Abstract

Recombinant tumor necrosis factor α (rTNFα; 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-α was inhibited when cells were treated with the protein synthesis inhibitor cycloheximide, the effects of rTNFα may be protein-synthesis-dependent. The dose of rTNFα that was optimal for up-regulation of EGF-R on glioma cells did not inhibit the growth of these cells.125I-labeled mAb 425 lysed glioma cells in culture following its internalization into the cells. After glioma cells had been treated with rTNFα, 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 rTNFα effects were specific to the EGF-R and did not affect unrelated glioma-associated antigens. In our previous clinical trials,125I-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with125I-labeled mAb 425 and rTNFα.

Key words: Epidermal growth factor receptor, Tumor necrosis factor, Gliomas

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