Isolation and characterization of a monoclonal antibody containing an extra heavy-light chain Fab arm
Isolation and characterization of a monoclonal antibody containing an extra heavy-light chain Fab arm
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DOI：
10.1080/19420862.2018.1438795
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发表时间：
2018-01-01
期刊：
影响因子：
5.3
通讯作者：
Ambrogelly, Alexandre
中科院分区：
文献类型：
--
作者：
Boyd, Dan;Ebrahimi, Arpa;Ambrogelly, Alexandre
分离和表征单克隆抗体（mAb）变体以了解其结构对功能的影响是早期候选物选择期间的典型活动，有助于降低临床开发风险。特别地，由于其潜在的免疫原性，致力于表征寡聚变体。我们在这里报告一个单克隆抗体的变体组成的一个典型的单克隆抗体单体与抗原结合片段（Fab）的臂从其Fc域截肢在一个非共价的方式。截短的重链在细胞系基因组中编码，并且可能是细胞系生成期间基因组重组的产物。Fab臂的添加导致效力的严重损失，表明其与单体的Fab结构域的相互作用。这种变体的存在可以通过适当的纯化步骤容易地减轻。
Isolation and characterization of monoclonal antibody (mAb) variants to understand the impact of their structure on function is a typical activity during early-stage candidate selection that contributes to derisking clinical development. In particular, efforts are devoted to characterizing oligomeric variants, owing to their potential immunogenic nature. We report here a mAb variant consisting of a canonical mAb monomer associated in a non-covalent fashion with an antigen-binding fragment (Fab) arm amputated from its Fc domain. The truncated heavy chain is encoded in the cell line genome and is the likely product of a genomic recombination during cell line generation. The addition of the Fab arm results in severe loss of potency, indicating its interaction with the Fab domain of the monomer. The presence of such a variant can easily be mitigated by an adequate purification step.