Use of immunotoxins in combination to inhibit clonogenic growth of human breast carcinoma cells.

Published

Journal Article

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 recombinantly 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.

Full Text

Duke Authors

Cited Authors

  • Yu, YH; Crews, JR; Cooper, K; Ramakrishnan, S; Houston, LL; Leslie, DS; George, SL; Lidor, Y; Boyer, CM; Ring, DB

Published Date

  • June 1, 1990

Published In

Volume / Issue

  • 50 / 11

Start / End Page

  • 3231 - 3238

PubMed ID

  • 2334918

Pubmed Central ID

  • 2334918

International Standard Serial Number (ISSN)

  • 0008-5472

Language

  • eng

Conference Location

  • United States