ANTI-TRANSFERRIN RECEPTOR ANTIBODY LINKED TO PSEUDOMONAS EXOTOXIN AS A MODEL IMMUNOTOXIN IN HUMAN OVARIAN-CARCINOMA CELL-LINES

  • 1 January 1985
    • journal article
    • research article
    • Vol. 45  (2) , 751-757
Abstract
The potential usefulness of immunotoxins in treating human ovarian carcinomas was evaluated. A monoclonal antibody against the human transferrin receptor was covalently linked to Pseudomonas exotoxin. The activity of this immunotoxin (anti-TFR-PE) was studied in 5 ovarian carcinoma cell lines, a breast carcinoma cell line (MCF-7) and in KB cells. The ovarian carcinoma cell lines included 1 previously established cell line (A1847) and 4 recent isolates obtained from the malignant ascites of patients with metastatic ovarian carcinoma (OVCAR cell lines). While all cell lines showed inhibition of protein synthesis by anti-TFR-PE, there were quantitative differences when the level of protein synthesis was assayed after a 12-h incubation with the immunotoxin. These differences resulted from different kinetics of anti-TFR-PE activity in the various cell lines. Higher levels of cellular binding and internalization of anti-TFR contributed to increased toxicity of anti-TFR-PE. Verapamil increased the rate of protein synthesis inhibition and enhanced the toxicity of anti-TFR-PE in the OVCAR cell lines.

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