A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens.
MAbs
; 3(6): 546-57, 2011.
Article
em En
| MEDLINE
| ID: mdl-22123055
ABSTRACT
Bispecific antibodies based on full-length antibody structures are more optimal than fragment-based formats because they benefit from the favorable properties of the Fc region. However, the homodimeric nature of Fc effectively imposes bivalent binding on all current full-length bispecific antibodies, an attribute that can result in nonspecific activation of cross-linked receptors. We engineered a novel bispecific format, referred to as mAb-Fv, that utilizes a heterodimeric Fc region to enable monovalent co-engagement of a second target antigen in a full-length context. mAb-Fv constructs co-targeting CD16 and CD3 were expressed and purified as heterodimeric species, bound selectively to their co-target antigens, and mediated potent cytotoxic activity by NK cells and T cells, respectively. The capacity to co-engage distinct target antigens simultaneously with different valencies is an improved feature for bispecific antibodies with promising therapeutic implications.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos Fc das Imunoglobulinas
/
Fragmentos de Imunoglobulinas
/
Receptores de IgG
/
Complexo CD3
/
Anticorpos Biespecíficos
/
Citotoxicidade Celular Dependente de Anticorpos
Tipo de estudo:
Evaluation_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
MAbs
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos