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A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines.

Publication ,  Journal Article
Crews, JR; Maier, LA; Yu, YH; Hester, S; O'Briant, K; Leslie, DS; DeSombre, K; George, SL; Boyer, CM; Argon, Y
Published in: Int J Cancer
July 9, 1992

In previous studies, combinations of immunotoxins reactive with different cell-surface antigens have exerted additive cytotoxicity against tumor cells in culture. In this report we describe a combination of 2 immunotoxins that produce synergistic cytotoxic activity. Recombinantly derived ricin A chain (RTA) was conjugated with murine monoclonal antibodies (MAbs) 317G5, 260F9, 454A12 and 741F8 that bound to cell-surface determinants of 42, 55, 180 (transferrin receptor) and 185 kDa (HER-2/neu) expressed by the SKBr3 human breast-cancer cell line. When inhibition of clonogenic growth was measured in a limiting dilution assay, the combination of 260F9-RTA and 454A12-RTA produced synergistic cytotoxic activity against SKBr3 and 2 other breast-cancer cell lines. All other combinations produced only additive inhibition of clonogenic growth. Simultaneous binding of 260F9 and 454A12 was not supra-additive, but sub-populations of cells which lacked one or the other antigen could be detected. Kinetic studies of internalization, using antibodies conjugated with gold particles, indicated that 454A12 remained within peripheral endosomes for a longer interval in the presence of 260F9. This change in the traffic of the transferrin receptor may contribute to synergy between 260F9-RTA and 454A12-RTA.

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Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

July 9, 1992

Volume

51

Issue

5

Start / End Page

772 / 779

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Ricin
  • Recombinant Proteins
  • Receptors, Transferrin
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Oncogene Proteins, Viral
  • Microscopy, Electron
  • Kinetics
 

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Crews, J. R., Maier, L. A., Yu, Y. H., Hester, S., O’Briant, K., Leslie, D. S., … Argon, Y. (1992). A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines. Int J Cancer, 51(5), 772–779. https://doi.org/10.1002/ijc.2910510518
Crews, J. R., L. A. Maier, Y. H. Yu, S. Hester, K. O’Briant, D. S. Leslie, K. DeSombre, S. L. George, C. M. Boyer, and Y. Argon. “A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines.Int J Cancer 51, no. 5 (July 9, 1992): 772–79. https://doi.org/10.1002/ijc.2910510518.
Crews JR, Maier LA, Yu YH, Hester S, O’Briant K, Leslie DS, et al. A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines. Int J Cancer. 1992 Jul 9;51(5):772–9.
Crews, J. R., et al. “A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines.Int J Cancer, vol. 51, no. 5, July 1992, pp. 772–79. Pubmed, doi:10.1002/ijc.2910510518.
Crews JR, Maier LA, Yu YH, Hester S, O’Briant K, Leslie DS, DeSombre K, George SL, Boyer CM, Argon Y. A combination of two immunotoxins exerts synergistic cytotoxic activity against human breast-cancer cell lines. Int J Cancer. 1992 Jul 9;51(5):772–779.
Journal cover image

Published In

Int J Cancer

DOI

ISSN

0020-7136

Publication Date

July 9, 1992

Volume

51

Issue

5

Start / End Page

772 / 779

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Ricin
  • Recombinant Proteins
  • Receptors, Transferrin
  • Receptor, erbB-2
  • Receptor, ErbB-2
  • Oncology & Carcinogenesis
  • Oncogene Proteins, Viral
  • Microscopy, Electron
  • Kinetics