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首页> 美国政府科技报告 >Engineering Anti-EGFR Antibodies for Treatment of Breast Cancers with Poor Prognosis
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Engineering Anti-EGFR Antibodies for Treatment of Breast Cancers with Poor Prognosis

机译：工程抗EGFR抗体治疗预后不良的乳腺癌

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To enhance in vivo efficacy of anti-EGFR full length IgG for treatment of basal breast cancers, the most aggressive subtypes, we have successfully employed molecular evolution approach to improve Fc binding affinity to Fc receptor that activates ADCC effect in our 2008 report. In the current report, we focus on the molecular evolution of Fc binding affinity to neonatal Fc receptor (FcRn), which modulates the half-life of IgG in vivo. In detail, we first expressed and purified soluble human FcRn in mammalian CHO expression system, then used human FcRn to select yeast-displayed library of Fc domain variants with random mutations. Several Fc domain variants were identified to bind human FcRn with enhanced affinity than wild-type Fc. We also found that by alternating FcRn and Fc gamma RIIIa/V158 in sorting, some variants exhibited higher binding affinity to both human FcRn and Fc gamma RIIIa/V158, which was not observed in previous studies improving the affinity to FcRn while losing the binding to Fc gamma RIIIa/V158. The Fc variants with improved affinity to both FcRn and Fc gamma RIIIa/V158 may show enhanced ADCC and prolonged half-life in vivo.

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