Anti-transferrin receptor antibody linked to Pseudomonas exotoxin as a model immunotoxin in human ovarian carcinoma cell lines.
The present in vitro study was performed to evaluate the potential usefulness of immunotoxins in treating human ovarian carcinomas. 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 five ovarian carcinoma cell lines, a breast carcinoma cell line (MCF-7), and in KB cells. The ovarian carcinoma cell lines included one previously established cell line (A1847) and four 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-hr 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 were shown to contribute to increased toxicity of anti-TFR-PE. Verapamil increased the rate of protein synthesis inhibition and thus enhanced the toxicity of anti-TFR-PE in the OVCAR cell lines.
Pirker
R
R
FitzGerald
D J
DJ
Hamilton
T C
TC
Ozols
R F
RF
Willingham
M C
MC
Pastan
I
I
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D001943:Breast Neoplasms / Q000628:therapy; D002460:Cell Line; D002470:Cell Survival; D003114:Colony-Forming Units Assay; D005098:Exotoxins / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D066298:In Vitro Techniques; D007700:Kinetics; D010051:Ovarian Neoplasms / Q000628:therapy*; D011956:Receptors, Cell Surface / Q000276:immunology*; D011990:Receptors, Transferrin; D013997:Time Factors; D014410:Tumor Stem Cell Assay; D014700:Verapamil / Q000494:pharmacology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D005098:Exotoxins; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014700:Verapamil; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A