PO.ET02.05 · 实验与分子治疗
从结合到桥联：完整的FcgammaR测定工具套件加速抗体治疗药物开发
Binding to bridging: Complete suite of FcgammaR assay tools accelerates antibody therapeutic development
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
抗体之所以是有效的治疗药物，是因为其与抗原结合的特异性，以及通过Fc效应功能（如抗体依赖性细胞介导的细胞毒性（ADCC）、抗体依赖性细胞吞噬作用（ADCP）和补体依赖性细胞毒性（CDC）），通过与NK细胞和巨噬细胞等免疫细胞相互作用来激活免疫反应的能力。然而，用于表征这些相互作用的传统方法变异性高且耗费人力。我们开发了一套用于表征抗体效应功能的发光测定，可在整个抗体开发过程中进行稳健、简化的测量：Lumit®结合免疫测定、用于ADCC/ADCP的Fc效应报告基因生物测定，以及使用经作用机制（MoA）验证的原代细胞的HiBiT靶细胞杀伤生物测定。我们展示了其在抗CD20生物类似药抗体中的应用，显示出从结合到功能性杀伤研究的一致排序。这些快速、高通量的测定支持可比性、稳定性和批次放行决策。
查看英文原文 English abstract
Antibodies are effective therapeutics because of their specificity in binding to an antigen and ability to activate an immune response through Fc effector functions like antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cell phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC) by engaging with immune cells like NK cells and macrophage. However, traditional methods for characterizing these interactions are highly variable and labor-intensive. We developed a suite of luminescent assays for characterizing antibody effector functions for robust, streamlined measurement across antibody development: Lumit® Binding Immunoassays, Fc Effector Reporter Bioassays for ADCC/ADCP, and HiBiT Target Cell Killing Bioassays using MoA-qualified primary cells. We demonstrate application to anti-CD20 biosimilar antibodies, showing concordant rank order from binding to functional killing studies. These rapid, high-throughput assays support comparability, stability, and lot-release decisions.
利益披露 Disclosure
D. Garvin, None..
K. Riching, None..
B. F. Binkowski, None..
R. Moravec, None..
P. Stecha, None..
R. Flemming, None..
B. Godat, None..
K. Hillman, None..
M. Urh, None.