单克隆抗体
抗体
蛋白质组
计算生物学
血浆蛋白结合
细胞
药物开发
药品
生物
化学
细胞生物学
免疫学
生物信息学
药理学
生物化学
作者
Diana M. Norden,Carmen Navia,Jonathan T. Sullivan,Benjamin J. Doranz
出处
期刊:mAbs
[Informa]
日期:2024-08-24
卷期号:16 (1)
标识
DOI:10.1080/19420862.2024.2393785
摘要
Specificity profiling is a requirement for monoclonal antibodies (mAbs) and antibody-directed biotherapeutics such as CAR-T cells prior to initiating human trials. However, traditional approaches to assess the specificity of mAbs, primarily tissue cross-reactivity studies, have been unreliable, leading to off-target binding going undetected. Here, we review the emergence of cell-based protein arrays as an alternative and improved assessment of mAb specificity. Cell-based protein arrays assess binding across the full human membrane proteome, ~6,000 membrane proteins each individually expressed in their native structural configuration within live or unfixed cells. Our own profiling indicates a surprisingly high off-target rate across the industry, with 33% of lead candidates displaying off-target binding. Moreover, about 20% of therapeutic mAbs in clinical development and currently on the market display off-target binding. Case studies and off-target rates at different phases of biotherapeutic drug approval suggest that off-target binding is likely a major cause of adverse events and drug attrition.
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