Discovery Biotherapeutics, Bristol Myers Squibb, Redwood City, California 94063, United States.
Frontier Medicines, South San Francisco, California 94080, United States.
Anal Chem. 2021 Dec 14;93(49):16474-16480. doi: 10.1021/acs.analchem.1c03548. Epub 2021 Dec 2.
Identification of antibodies targeting diverse functional epitopes on an antigen is highly crucial for discovering effective therapeutic candidates. Employing a traditional stepwise antibody "screening funnel" as well as prioritizing affinity-based selections over epitope-based selections, result in lead antibody panels lacking epitope diversity. In the present study, we employed an array-based surface plasmon resonance (SPR) platform to perform high-throughput epitope binning analysis on a large number of monoclonal antibodies (mAbs) generated in the early drug discovery process. The mAb panel contained clones from different antibody generation techniques and diverse transgenic mouse strains. The epitope binning results were analyzed in unique ways using various visualizations in the form of dendrograms and network plots, which assisted in determining diversity and redundancy in the mAb sample set. The binning data were further integrated with affinity information to evaluate the performance of seven different transgenic mouse strains. The combination of epitope binning results with binding kinetics and sequence analysis provided an effective and efficient way of selecting high affinity antibodies representing a diverse set of sequence families and epitopes.
鉴定针对抗原上不同功能表位的抗体对于发现有效的治疗候选物至关重要。采用传统的逐步抗体“筛选漏斗”，并优先进行基于亲和力的选择而不是基于表位的选择，导致先导抗体面板缺乏表位多样性。在本研究中，我们采用基于阵列的表面等离子体共振（SPR）平台，对早期药物发现过程中产生的大量单克隆抗体（mAb）进行高通量表位分组分析。mAb 面板包含来自不同抗体生成技术和不同转基因小鼠品系的克隆。使用树状图和网络图等各种可视化形式，以独特的方式分析表位分组结果，有助于确定 mAb 样本集中的多样性和冗余性。进一步将分组数据与亲和力信息集成，以评估七种不同转基因小鼠品系的性能。将表位分组结果与结合动力学和序列分析相结合，为选择代表多种序列家族和表位的高亲和力抗体提供了一种有效且高效的方法。
