HER/erbB receptors as therapeutic targets of immunotoxins in human rhabdomyosarcoma cells

Cinzia Ricci, Letizia Polito, Patrizia Nanni, Lorena Landuzzi, Annalisa Astolfi, Giordano Nicoletti, Ilaria Rossi, Carla De Giovanni, Andrea Bolognesi, Pier Luigi Lollini

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Abstract

Human rhabdomyosarcoma cells express HER/erbB growth factors receptors. Receptors belonging to this family are overexpressed and play a role in many types of epithelial and neural cancer and have been selected as targets for cancer therapy. In this paper EGF-R, HER-2 and HER-3 receptors were tested as therapeutic targets of immunotoxins in human rhabdomyosarcoma. Rhabdomyosarcoma cells were treated with indirect immunotoxins consisting in primary specific murine monoclonal antibodies recognizing EGF-R, HER-2 and HER-3 followed by secondary F(ab′)2 antimouse immunoglobulin linked to saporin-S6, a type 1 ribosome-inactivating protein (RIP) from the seeds of Saponaria officinalis. The indirect immunotoxin targeting EGF-R caused a significant inhibition in cell growth and protein synthesis and a strong increase in apoptosis in rhabdomyosarcoma cells, whereas indirect immunotoxins against HER-2 and HER-3 were ineffective. The toxic activity of anti-EGF-R immunotoxin was also observed on rhabdomyosarcoma cells expressing low level of EGF-R. EGF-R could be a novel therapeutic target of immunotoxins in human rhabdomyosarcoma.

Original languageEnglish
Pages (from-to)314-323
Number of pages10
JournalJournal of Immunotherapy
Volume25
Issue number4
DOIs
Publication statusPublished - 2002

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Keywords

  • Apoptosis
  • HER/ErbB receptors
  • Immunotoxins
  • Protein synthesis
  • Rhabdomyosarcoma

ASJC Scopus subject areas

  • Cancer Research
  • Immunology
  • Pharmacology

Cite this

Ricci, C., Polito, L., Nanni, P., Landuzzi, L., Astolfi, A., Nicoletti, G., Rossi, I., De Giovanni, C., Bolognesi, A., & Lollini, P. L. (2002). HER/erbB receptors as therapeutic targets of immunotoxins in human rhabdomyosarcoma cells. Journal of Immunotherapy, 25(4), 314-323. https://doi.org/10.1097/00002371-200207000-00003