scFv-based "Grababody" as a general strategy to improve recruitment of immune effector cells to antibody-targeted tumors.
Cancer Res
; 73(8): 2619-27, 2013 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-23396586
ABSTRACT
Recruitment of immune cells to tumor cells targeted by a therapeutic antibody can heighten the antitumor efficacy of the antibody. For example, p185(her2/neu)-targeting antibodies not only downregulate the p185(her2/neu) kinase (ERBB2) but also trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC) through the antibody Fc region. Here, we describe a generalized strategy to improve immune cell recruitment to targeted cancer cells, using a modified scFv antibody we call a "Grababody" that binds the target protein and endogenous immunoglobulins. The model system we used to illustrate the use of this platform recognizes p185(her2/neu) and includes an IgG binding domain. The recombinant scFv Grababody that was created recruited circulating human IgGs and attracted immune cells carrying Fc receptors to tumor cells that expressed p185(her2/neu). The presence of the IgG binding domain significantly enhanced CDC and ADCC activity and improved antitumor activity in vivo. Our results illustrate a novel general approach to improve antibody-like proteins for therapeutic applications.
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Base de dados:
MEDLINE
Assunto principal:
Anticorpos de Cadeia Única
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Anticorpos Antineoplásicos
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Citotoxicidade Celular Dependente de Anticorpos
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Neoplasias
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article