Increasing Serum Half-life and Extending Cholesterol Lowering in Vivo by Engineering Antibody with pH-sensitive Binding to PCSK9
Increasing Serum Half-life and Extending Cholesterol Lowering in Vivo by Engineering Antibody with pH-sensitive Binding to PCSK9
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DOI：
10.1074/jbc.m111.319764
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发表时间：
2012-03-30
影响因子：
4.8
通讯作者：
Rajpal, Arvind
中科院分区：
文献类型：
--
作者：
Chaparro-Riggers, Javier;Liang, Hong;Rajpal, Arvind
背景：拮抗性抗PCSK9抗体具有靶向清除作用，产生剂量依赖的PK值。结果：设计一种与PCSK9结合具有pH敏感性的抗体可减少靶向介导的清除，从而增加PK和体内疗效。结论：pH敏感的抗PCSK9抗体是很好的治疗开发候选抗体。意义：pH敏感的抗体可以减少或减少受靶向介导的清除和高抗原负载阻碍的抗体的使用。
Background: An antagonistic anti-PCSK9 antibody exhibits target- mediated clearance, resulting in a dose-dependent PK.Results: Engineering of an antibody with pH-sensitive binding to PCSK9 decreases target-mediated clearance, resulting in increased PK and efficacy in vivo.Conclusion: pH-sensitive anti-PCSK9 antibodies are excellent candidates for therapeutic development.Significance: pH-sensitive antibodies may enable less frequent or lower dosing of antibodies hampered by target-mediated clearance and high antigen load.