Site-Specific Conjugation of Native Antibodies Using Engineered Microbial Transglutaminases.
Bioconjug Chem
; 31(4): 1070-1076, 2020 04 15.
Article
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| MEDLINE
| ID: mdl-32134638
ABSTRACT
Site-specific bioconjugation technologies are frequently employed to generate homogeneous antibody-drug conjugates (ADCs) and are generally considered superior to stochastic approaches like lysine coupling. However, most of the technologies developed so far require undesired manipulation of the antibody sequence or its glycan structures. Herein, we report the successful engineering of microbial transglutaminase enabling efficient, site-specific conjugation of drug-linker constructs to position HC-Q295 of native, fully glycosylated IgG-type antibodies. ADCs generated via this approach demonstrate excellent stability in vitro as well as strong efficacy in vitro and in vivo. As it employs different drug-linker structures and several native antibodies, our study additionally proves the broad applicability of this approach.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Ingeniería de Proteínas
/
Transglutaminasas
/
Inmunoconjugados
Idioma:
En
Revista:
Bioconjug Chem
Asunto de la revista:
BIOQUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania