Use of Immunotoxins in Combination to Inhibit Clonogenic Growth of Human Breast Carcinoma Cells1

Y. H. Yu, J. R. Crews, K. Cooper, Sundaram Ramakrishnan, D. S. Leslie, Y. Lidor, C. M. Boyer, R. C. Bast, S. L. George, R. C. Bast, L. L. Houston, D. B. Ring

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Substantial heterogeneity has been observed in the expression of individual antigens within tumor cell populations. Immunotoxins which bind to different cell surface antigens might exert additive or synergistic cytotoxicity when used in combination to eliminate all clonogenic cells within a tumor. Immunotoxins have been prepared by conjugating recombinanty derived toxin A chain to different monoclonal reagents which recognize cell surface determinants of Mr 42,000 (317G5), 55,000 (260F9), and 200,000 (741F8). Each immunotoxin was evaluated for binding, internalization, and cytotoxicity with four breast cancer cell lines. Each of the three immunotoxins bound to the SKBr3 cell line and exerted antitumor activity in a limiting dilution clonogenic assay. Simultaneous treatment with two immunotoxins produced additive antitumor activity with each of the possible combinations. Additive binding could be demonstrated by immunofluorescent techniques, however, with only one of three combinations. With two of the three combinations, subpopulations of tumor cells could be identified which lacked one or the other antigenic determinant but not both. Consequently, log-additive antitumor activity was produced by immunotoxins in combination, and heterogeneity of antigenic targets may have contributed to the combined cytotoxicity in some but not all cases.

Original languageEnglish (US)
Pages (from-to)3231-3238
Number of pages8
JournalCancer Research
Volume50
Issue number11
StatePublished - Jun 1 1990
Externally publishedYes

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Immunotoxins
Breast Neoplasms
Growth
Cell Line
Neoplasm Antigens
Surface Antigens
Epitopes
Neoplasms
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Yu, Y. H., Crews, J. R., Cooper, K., Ramakrishnan, S., Leslie, D. S., Lidor, Y., ... Ring, D. B. (1990). Use of Immunotoxins in Combination to Inhibit Clonogenic Growth of Human Breast Carcinoma Cells1. Cancer Research, 50(11), 3231-3238.

Use of Immunotoxins in Combination to Inhibit Clonogenic Growth of Human Breast Carcinoma Cells1. / Yu, Y. H.; Crews, J. R.; Cooper, K.; Ramakrishnan, Sundaram; Leslie, D. S.; Lidor, Y.; Boyer, C. M.; Bast, R. C.; George, S. L.; Bast, R. C.; Houston, L. L.; Ring, D. B.

In: Cancer Research, Vol. 50, No. 11, 01.06.1990, p. 3231-3238.

Research output: Contribution to journalArticle

Yu, YH, Crews, JR, Cooper, K, Ramakrishnan, S, Leslie, DS, Lidor, Y, Boyer, CM, Bast, RC, George, SL, Bast, RC, Houston, LL & Ring, DB 1990, 'Use of Immunotoxins in Combination to Inhibit Clonogenic Growth of Human Breast Carcinoma Cells1', Cancer Research, vol. 50, no. 11, pp. 3231-3238.
Yu YH, Crews JR, Cooper K, Ramakrishnan S, Leslie DS, Lidor Y et al. Use of Immunotoxins in Combination to Inhibit Clonogenic Growth of Human Breast Carcinoma Cells1. Cancer Research. 1990 Jun 1;50(11):3231-3238.
Yu, Y. H. ; Crews, J. R. ; Cooper, K. ; Ramakrishnan, Sundaram ; Leslie, D. S. ; Lidor, Y. ; Boyer, C. M. ; Bast, R. C. ; George, S. L. ; Bast, R. C. ; Houston, L. L. ; Ring, D. B. / Use of Immunotoxins in Combination to Inhibit Clonogenic Growth of Human Breast Carcinoma Cells1. In: Cancer Research. 1990 ; Vol. 50, No. 11. pp. 3231-3238.
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