Epitope Mapping for a Preclinical Bevacizumab (Avastin) Biosimilar on an Extended Construct of Vascular Endothelial Growth Factor A Using Millisecond Hydrogen-Deuterium Exchange Mass Spectrometry.
Biochemistry
; 59(30): 2776-2781, 2020 08 04.
Article
em En
| MEDLINE
| ID: mdl-32672953
ABSTRACT
The success of bevacizumab (Avastin), a monoclonal antibody (mAb) anticancer drug targeting vascular endothelial growth factor A (VEGF-A), has motivated the development of biosimilars. Establishing target epitope similarity using epitope mapping is a critical step in preclinical mAb biosimilar development. Here we use time-resolved electrospray ionization hydrogen-deuterium exchange (HDX) mass spectrometry to rapidly compare the epitopes of commercial Avastin and a biosimilar in preclinical development (ApoBev) on an extended construct of VEGF-A. The Avastin and ApoBev epitopes determined in our experiments agree with each other and with the known epitope derived from the Avastin Fab domain/truncated VEGF co-crystal structure. However, subtly different allosteric effects observed exclusively at short (millisecond) HDX labeling times may reflect a slightly different binding mode for ApoBev.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Mapeamento de Epitopos
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Fator A de Crescimento do Endotélio Vascular
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Medicamentos Biossimilares
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Bevacizumab
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Espectrometria de Massa com Troca Hidrogênio-Deutério
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article