Abstract
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 × 10-9 to 1.8 × 10-8 m. In contrast, no significant inhibition of leucine incorporation was observed when anti-TfR-A was tested on rat cells (IC50 > 10-7 m) or when a control immunotoxin directed against carcinoembryonic antigen was substituted for anti-TfR-A on human glioma cells (IC50 > 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 × 10-12 to 1.5 × 10-10 m). In contrast, an IC50 of > 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.
Footnotes
-
↵1 Supported in part by Grants CA 49254 and CA 39748 from the National Cancer Institute and a grant from the Joseph P. Healy Foundation.
-
↵2 To whom requests for reprints should be addressed, at Department of Neurology, University of Massachusetts Medical Center, 55 Lake Ave. North, Worcester, MA 01655.
- Received April 10, 1990.
- Accepted July 13, 1990.
- ©1990 American Association for Cancer Research.
Volume 50, Issue 20
