Department of Neurology; Department of Medicine
Antibodies, Monoclonal; Drug Synergism; Glioma; Humans; Immunotoxins; Male; Middle Aged; Monensin; Receptors, Transferrin; Ricin; Tumor Cells, Cultured
Cancer Biology | Medical Neurobiology | Neurology
The cytotoxic effects of an antihuman transferrin receptor monoclonal antibody-ricin A-chain conjugate (anti-TfR-A) immunotoxin on glioma cells were assessed in vitro. Five human glioma cell lines were studied; three were derived from surgical explants (MG-1, MG-2, MG-3) and two were well characterized established glioma cells (U-87 MG, U-373 MG). The C6 rat glioma line served as a nonhuman control. One of six lines (U-373) expressed glial fibrillary acidic protein, as assessed by immunohistochemistry. All five human lines expressed human transferrin receptor, as assessed by flow cytometry; no human transferrin receptor was demonstrable on rat C6 cells. Potent inhibition of protein synthesis was found after an 18-h incubation with anti-TfR-A. Fifty % inhibitory concentration (IC50) values for human glioma cells ranged from 1.9 X 10(-9) to 1.8 X 10(-8) M. In contrast, no significant inhibition of leucine incorporation was observed when anti-TfR-A was tested on rat cells (IC50 greater than 10(-7) M) or when a control immunotoxin directed against carcinoembryonic antigen was substituted for anti-TfR-A on human glioma cells (IC50 greater than 10(-7) M). Coincubation with the carboxylic ionophore monensin (10(-7) M) decreased the IC50 of anti-TfR-A against human glioma lines from 16- to 842-fold (range, 7.0 X 10(-12) to 1.5 X 10(-10) M). In contrast, an IC50 of greater than 10(-7) M was obtained when C6 cells were incubated with anti-TfR-A and monensin. Anti-TfR-A immunotoxins potentiated by monensin are extremely potent in vitro cytotoxins for human glioma cells.
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Citation: Cancer Res. 1990 Oct 15;50(20):6696-700.
Recht, Lawrence D.; Griffin, Thomas W.; Raso, Vic; and Salimi, Ali R., "Potent cytotoxicity of an antihuman transferrin receptor-ricin A-chain immunotoxin on human glioma cells in vitro" (1990). Open Access Articles. 377.