Production and characterization of a humanized single-chain antibody against human integrin alphav beta3 protein.
J Biol Chem
; 286(27): 24500-7, 2011 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-21606501
ABSTRACT
Anti-angiogenesis therapy is an emerging strategy for cancer treatment. This therapy has many advantages over existing treatments, such as fewer side effects, fewer resistance problems, and a broader tumor type spectrum. Integrin αvß3 is a heterodimeric transmembrane glycoprotein that has been demonstrated to play a key role in tumor angiogenesis and metastasis. We have used a phage antibody display to humanize a mouse monoclonal antibody (mAb E10) against human integrin αvß3 with a predetermined CDR3 gene. Three human phage antibodies were developed. Analysis of the humanized phage antibodies by phage ELISA revealed that the antibodies retained high antigen-binding activity and detected the same epitope as the parent mAb E10. A humanized single chain Fv (scFv) antibody was expressed in Escherichia coli in a soluble form. Analysis of the purified scFv indicated that it has the same specificity and affinity as the original mAb. Cell viability assays and xenograft model results suggested that the humanized scFv possesses anti-tumor growth activity in vitro and in vivo. This successful production of a humanized scFv with the ability to inhibit αvß3-mediated cancer cell growth may provide a novel candidate for integrin αvß3-targeted therapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regiões Determinantes de Complementaridade
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Integrina alfaVbeta3
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Anticorpos de Cadeia Única
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Anticorpos Monoclonais Murinos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article