Characterization of cytotoxic activity of saporin anti-GP185/HER-2 immunotoxins

R. Tecce, G. Digiesi, A. Savarese, D. Trizio, P. G. Natali

Research output: Contribution to journalArticle

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Abstract

The oncogene HER-2/neu encodes a trans-membrane receptor of 185 kDa with tyrosine-kinase activity. Over-expression of this molecule has been reported in a significant proportion of human breast and ovarian carcinomas, characterized by a poor clinical prognosis. Two monoclonal antibodies (MAbs), recognizing distinct epitopes of the gp 185 extracellular domain, have been utilized in the present study for the production of immunotoxins (ITs) by conjugation to the type-I RIP (ribosome-inactivating protein) plant toxin saporin 6 (SAP). These ITs have been shown to retain tumor-specificity and specifically to inhibit protein synthesis in the gp 185(HER-2(+)) SK-BR-3 breast-carcinoma cell line with IC50 values lower then 1 nM. Kinetics of the cytotoxic activity of the ITs are characterized by a slow rate, since incubation times ranging from 24 to 60 hr, depending on the different degree of expression of the receptor, are required to determine >90% inhibition in the incorporation of radiolabeled leucine. However, the cytotoxic activity of these ITs, as evaluated by a more sensitive clonogenic assay, appears highly potent, since we have observed that 3 to 4 logs of cells are killed upon exposure to the ITs for short times at concentrations ranging from 1 to 5 x 10-8 M.

Original languageEnglish
Pages (from-to)122-127
Number of pages6
JournalInternational Journal of Cancer
Volume55
Issue number1
Publication statusPublished - 1993

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Immunotoxins
Ribosome Inactivating Proteins
Breast Neoplasms
Oncogenes
Leucine
Protein-Tyrosine Kinases
Inhibitory Concentration 50
Epitopes
Monoclonal Antibodies
saporin
Cell Line
Membranes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Characterization of cytotoxic activity of saporin anti-GP185/HER-2 immunotoxins. / Tecce, R.; Digiesi, G.; Savarese, A.; Trizio, D.; Natali, P. G.

In: International Journal of Cancer, Vol. 55, No. 1, 1993, p. 122-127.

Research output: Contribution to journalArticle

Tecce, R, Digiesi, G, Savarese, A, Trizio, D & Natali, PG 1993, 'Characterization of cytotoxic activity of saporin anti-GP185/HER-2 immunotoxins', International Journal of Cancer, vol. 55, no. 1, pp. 122-127.
Tecce, R. ; Digiesi, G. ; Savarese, A. ; Trizio, D. ; Natali, P. G. / Characterization of cytotoxic activity of saporin anti-GP185/HER-2 immunotoxins. In: International Journal of Cancer. 1993 ; Vol. 55, No. 1. pp. 122-127.
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