Agonist antibody discovery: Experimental, computational, and rational engineering approaches.
Agonist antibody discovery: Experimental, computational, and rational engineering approaches.
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DOI：
10.1016/j.drudis.2021.09.008
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发表时间：
2022-01
影响因子：
7.4
通讯作者：
Tessier PM
中科院分区：
文献类型：
--
作者：
Schardt JS;Jhajj HS;O'Meara RL;Lwo TS;Smith MD;Tessier PM
激活细胞信号的激动剂抗体已成为治疗多种疾病的有希望的治疗药物。不幸的是，具有所需激动剂功能的稀有抗体的发现是药物开发的主要瓶颈。然而，最近在发现和优化针对各种治疗靶点的激动剂抗体方面取得了重要进展，这些抗体由不同的信号机制激活。在此，我们综述了用于激动剂抗体发现的新的高通量实验和计算方法，以及优化其激动剂活性的合理分子工程方法。
Agonist antibodies that activate cellular signaling have emerged as promising therapeutics for treating myriad pathologies. Unfortunately, the discovery of rare antibodies with the desired agonist functions is a major bottleneck during drug development. Nevertheless, there has been important recent progress in discovering and optimizing agonist antibodies against a variety of therapeutic targets that are activated by diverse signaling mechanisms. Herein, we review emerging high-throughput experimental and computational methods for agonist antibody discovery as well as rational molecular engineering methods for optimizing their agonist activity.
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