Characterization of cytotoxic activity of saporin anti-gp185/HER-2 immunotoxins.
Int J Cancer
; 55(1): 122-7, 1993 Aug 19.
Article
en En
| MEDLINE
| ID: mdl-8102128
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-1 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 gp185HER-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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Plantas
/
Inmunotoxinas
/
Proteínas Proto-Oncogénicas
/
Antineoplásicos
/
N-Glicosil Hidrolasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Cancer
Año:
1993
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
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ESTADOS UNIDOS DA AMERICA
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EUA
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UNITED STATES
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UNITED STATES OF AMERICA
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US
/
USA