De novo isolation of antibodies with pH-dependent binding properties
De novo isolation of antibodies with pH-dependent binding properties
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DOI：
10.1080/19420862.2015.1006993
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发表时间：
2015-03-01
期刊：
影响因子：
5.3
通讯作者：
Fischer, Nicolas
中科院分区：
文献类型：
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作者：
Bonvin, Pauline;Venet, Sophie;Fischer, Nicolas
pH依赖性抗体被设计成在微酸性pH下释放它们的靶标，这一特性使它们适合临床和生物技术应用。这种抗体以前是通过对预先存在的抗体进行组氨酸扫描获得的，这是一种劳动密集型的策略，导致抗体在pH 6.0时显示出与靶标的残留结合。我们在这里报告了通过噬菌体展示从富含组氨酸的文库中选择ph依赖性抗体的从头分离。通过这种方法分离出了对CXCL10具有不同亲和力的强ph依赖性克隆。我们的最佳候选物在pH为7.2时对CXCL10具有纳摩尔亲和力，但在pH为6.0时没有检测到残留的结合。因此，我们认为这种新工艺是产生ph依赖性抗体的有效策略。
pH-dependent antibodies are engineered to release their target at a slightly acidic pH, a property making them suitable for clinical as well as biotechnological applications. Such antibodies were previously obtained by histidine scanning of pre-existing antibodies, a labor-intensive strategy resulting in antibodies that displayed residual binding to their target at pH 6.0. We report here the de novo isolation of pH-dependent antibodies selected by phage display from libraries enriched in histidines. Strongly pH-dependent clones with various affinity profiles against CXCL10 were isolated by this method. Our best candidate has nanomolar affinity for CXCL10 at pH 7.2, but no residual binding was detected at pH 6.0. We therefore propose that this new process is an efficient strategy to generate pH-dependent antibodies.