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. 125I-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, 125I-labeled mAb 425 showed immunotherapeutic effects in glioma patients. The present study provides the basis for considerations of combined immunotherapy of glioma patients with 125I-labeled mAb 425 and rTNF alpha.
Adachi
K
K
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104.
Belser
P
P
Bender
H
H
Li
D
D
Rodeck
U
U
Benveniste
E N
EN
Woo
D
D
Schmiegel
W H
WH
Herlyn
D
D
D000911:Antibodies, Monoclonal; D001254:Astrocytoma / Q000378:metabolism / Q000628:therapy / Q000648:ultrastructure; D002455:Cell Division / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000187:drug effects* / Q000502:physiology*; D005910:Glioma / Q000378:metabolism / Q000628:therapy / Q000648:ultrastructure*; D006801:Humans; D007167:Immunotherapy; D000922:Immunotoxins / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology / Q000633:toxicity; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000633:toxicity; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D066246:ErbB Receptors