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

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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 ( IF 2.9 ) Pub Date : 2020-07-16 , DOI: 10.1021/acs.biochem.0c00308
Kerene A Brown _{1,

2} , Cristina Lento _{1,

2} , Shanthi Rajendran ₃ , Jason Dowd ₄ , Derek J Wilson _{1,

2}

Affiliation

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.

中文翻译：

临床前贝伐单抗（Avastin）生物仿制药在毫秒级氢-氘交换质谱法扩展构建的血管内皮生长因子A上的表位作图。

贝伐单抗（Avastin）是一种针对血管内皮生长因子A（VEGF-A）的单克隆抗体（mAb）抗癌药物，它的成功推动了生物仿制药的发展。使用表位作图建立目标表位相似性是临床前mAb生物仿制药开发的关键步骤。在这里，我们使用时间分辨电喷雾电离氢-氘交换（HDX）质谱法，在扩展的VEGF-A构建体上快速比较商品化的Avastin和临床前开发的生物仿制药（ApoBev）的表位。在我们的实验中确定的Avastin和ApoBev表位彼此一致，并且与衍生自Avastin Fab结构域/截短的VEGF共晶体结构的已知表位一致。然而，

更新日期：2020-08-04

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