Rational selection of building blocks for the assembly of bispecific antibodies.
MAbs
; 13(1): 1870058, 2021.
Article
en En
| MEDLINE
| ID: mdl-33397191
ABSTRACT
Bispecific antibodies, engineered to recognize two targets simultaneously, demonstrate exceptional clinical potential for the therapeutic intervention of complex diseases. However, these molecules are often composed of multiple polypeptide chains of differing sequences. To meet industrial scale productivity, enforcing the correct quaternary assembly of these chains is critical. Here, we describe Chain Selectivity Assessment (CSA), a high-throughput method to rationally select parental monoclonal antibodies (mAbs) to make bispecific antibodies requiring correct heavy/light chain pairing. By deploying CSA, we have successfully identified mAbs that exhibit a native preference toward cognate chain pairing that enables the production of hetero-IgGs without additional engineering. Furthermore, CSA also identified rare light chains (LCs) that permit positive binding of the non-cognate arm in the common LC hetero-IgGs, also without engineering. This rational selection of parental mAbs with favorable developability characteristics is critical to the successful development of bispecific molecules with optimal manufacturability properties.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Inmunoglobulina G
/
Cadenas Pesadas de Inmunoglobulina
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Cadenas Ligeras de Inmunoglobulina
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Anticuerpos Biespecíficos
/
Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
MAbs
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2021
Tipo del documento:
Article