A two-in-one antibody against HER3 and EGFR has superior inhibitory activity compared with monospecific antibodies.
Cancer Cell
; 20(4): 472-86, 2011 Oct 18.
Article
em En
| MEDLINE
| ID: mdl-22014573
ABSTRACT
Extensive crosstalk among ErbB/HER receptors suggests that blocking signaling from more than one family member may be essential to effectively treat cancer and limit drug resistance. We generated a conventional IgG molecule MEHD7945A with dual HER3/EGFR specificity by phage display engineering and used structural and mutational studies to understand how a single antigen recognition surface binds two epitopes with high affinity. As a human IgG1, MEHD7945A exhibited dual action by inhibiting EGFR- and HER3-mediated signaling in vitro and in vivo and the ability to engage immune effector functions. Compared with monospecific anti-HER antibodies, MEHD7945A was more broadly efficacious in multiple tumor models, showing that combined inhibition of EGFR and HER3 with a single antibody is beneficial.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Imunoglobulina G
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Anticorpos Biespecíficos
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Receptor ErbB-3
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Receptores ErbB
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Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Female
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Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article