Expression of an oncogenic mutant EGF receptor markedly increases the sensitivity of cells to an EGF-receptor-specific antibody-toxin.
Int J Cancer
; 75(6): 878-84, 1998 Mar 16.
Article
em En
| MEDLINE
| ID: mdl-9506533
ABSTRACT
EGFRvIII is a ligand-independent, constitutively active variant of the epidermal growth factor receptor (EGFR) that is specifically expressed in gliomas and various other human malignancies and has been proposed as a target for directed tumor therapy. We have recently constructed a highly potent single-chain antibody-toxin, scFv(14E1)-ETA, which consists of the variable domains of the antibody 14E1 specific for human full-length EGFR genetically fused to a truncated form of Pseudomonas exotoxin A. We demonstrate here binding of 14E1 antibody to both full-length and variant EGFR. In contrast to a recombinant toxin containing transforming growth factor-alpha (TGF-alpha) as a cell targeting domain, scFv(14E1)-ETA was highly active on cells expressing EGFRvIII. Surprisingly, scFv(14E1)-ETA displayed cell killing activity on EGFRvIII-expressing cells that was up to 100-fold higher than on control cells expressing full-length EGFR. No differences in the binding affinities of scFv(14E1)-ETA to full-length EGFR or EGFRvIII were observed, suggesting that events downstream of immunotoxin binding are responsible for the increased sensitivity of EGFRvIII-expressing cells. This might have implications for the development of therapeutic reagents simultaneously targeting different forms of the EGFR.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Imunotoxinas
/
Receptores ErbB
/
Anticorpos Monoclonais
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
1998
Tipo de documento:
Article