Characterization of immunotoxins active against ovarian cancer cell lines

R. Pirker, D. J P FitzGerald, T. C. Hamilton, R. F. Ozols, W. Laird, A. E. Frankel, M. C. Willingham, I. Pastan

Research output: Contribution to journalArticle

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Abstract

The purpose of the present study was to develop immunotoxins directed against human ovarian carcinoma cells. Four monoclonal antibodies (260F9, 454C11, 280D11, and 245E7) were chosen because they were found to bind to various ovarian carcinoma cell lines. These antibodies were covalently linked to either Pseudomonas exotoxin (PE) or ricin A chain (RTA), and the conjugates were tested against five ovarian cancer cell lines (OVCAR-2, -3, -4, -5; A1847). The ability of the immunotoxins to inhibit both protein synthesis and colony formation was evaluated. Qualitatively similar results were obtained for both types of assays. Usually, PE conjugates were more toxic than their corresponding RTA conjugates. 454C11-PE was very toxic for all ovarian carcinoma lines, whereas 454C11-RTA had low activity. Both 260F9-PE and 260F9-RTA were active in all OVCAR cell lines but not in A1847 cells. 280D11-PE was toxic for OVCAR-4; otherwise, 280D11-PE and RTA conjugates of both 280D11 and 245E7 had little activity. Specificity of immunotoxin action was shown by competition by excess antibody, nontoxicity in nontarget cells, and inactivity of an irrelevant immunotoxin. To investigate the basis of antibody-dependent differences in activity of the various immunotoxins, antibody uptake was studied in OVCAR-2 cells, and the results indicate that antibody internalization is one important factor in the activity of immunotoxins.

Original languageEnglish (US)
Pages (from-to)1261-1267
Number of pages7
JournalJournal of Clinical Investigation
Volume76
Issue number3
StatePublished - 1985

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Immunotoxins
Exotoxins
Pseudomonas
Ovarian Neoplasms
Cell Line
Poisons
Antibodies
Carcinoma
Ricin
Monoclonal Antibodies
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Pirker, R., FitzGerald, D. J. P., Hamilton, T. C., Ozols, R. F., Laird, W., Frankel, A. E., ... Pastan, I. (1985). Characterization of immunotoxins active against ovarian cancer cell lines. Journal of Clinical Investigation, 76(3), 1261-1267.

Characterization of immunotoxins active against ovarian cancer cell lines. / Pirker, R.; FitzGerald, D. J P; Hamilton, T. C.; Ozols, R. F.; Laird, W.; Frankel, A. E.; Willingham, M. C.; Pastan, I.

In: Journal of Clinical Investigation, Vol. 76, No. 3, 1985, p. 1261-1267.

Research output: Contribution to journalArticle

Pirker, R, FitzGerald, DJP, Hamilton, TC, Ozols, RF, Laird, W, Frankel, AE, Willingham, MC & Pastan, I 1985, 'Characterization of immunotoxins active against ovarian cancer cell lines', Journal of Clinical Investigation, vol. 76, no. 3, pp. 1261-1267.
Pirker R, FitzGerald DJP, Hamilton TC, Ozols RF, Laird W, Frankel AE et al. Characterization of immunotoxins active against ovarian cancer cell lines. Journal of Clinical Investigation. 1985;76(3):1261-1267.
Pirker, R. ; FitzGerald, D. J P ; Hamilton, T. C. ; Ozols, R. F. ; Laird, W. ; Frankel, A. E. ; Willingham, M. C. ; Pastan, I. / Characterization of immunotoxins active against ovarian cancer cell lines. In: Journal of Clinical Investigation. 1985 ; Vol. 76, No. 3. pp. 1261-1267.
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