A semi high-throughput method for screening small bispecific antibodies with high cytotoxicity.
Sci Rep
; 7(1): 2862, 2017 06 06.
Article
en En
| MEDLINE
| ID: mdl-28588218
ABSTRACT
Small bispecific antibodies that induce T-cell-mediated cytotoxicity have the potential to damage late-stage tumor masses to a clinically relevant degree, but their cytotoxicity is critically dependent on their structural and functional properties. Here, we constructed an optimized procedure for identifying highly cytotoxic antibodies from a variety of the T-cell-recruiting antibodies engineered from a series of antibodies against cancer antigens of epidermal growth factor receptor family and T-cell receptors. By developing and applying a set of rapid operations for expression vector construction and protein preparation, we screened the cytotoxicity of 104 small antibodies with diabody format and identified some with 103-times higher cytotoxicity than that of previously reported active diabody. The results demonstrate that cytotoxicity is enhanced by synergistic effects between the target, epitope, binding affinity, and the order of heavy-chain and light-chain variable domains. We demonstrate the importance of screening to determine the critical rules for highly cytotoxic antibodies.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Ensayos de Selección de Medicamentos Antitumorales
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Anticuerpos Biespecíficos
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Ensayos Analíticos de Alto Rendimiento
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Antineoplásicos Inmunológicos
Tipo de estudio:
Diagnostic_studies
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Prognostic_studies
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Screening_studies
Límite:
Humans
Idioma:
En
Año:
2017
Tipo del documento:
Article