A Bispecific Antibody Based on Pertuzumab Fab Has Potent Antitumor Activity
A Bispecific Antibody Based on Pertuzumab Fab Has Potent Antitumor Activity
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DOI：
10.1097/cji.0000000000000200
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发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Wang, Zhong
中科院分区：
文献类型：
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作者：
Deng, Wentong;Liu, Jiayu;Wang, Zhong
人表皮生长因子受体2（HER 2）在转移性乳腺癌中经常过表达和激活。靶向Her 2的单克隆抗体，如曲妥珠单抗和帕妥珠单抗，已成为HER 2阳性乳腺癌患者的重要靶向治疗。曲妥珠单抗和帕妥珠单抗均可通过抑制Her 2信号传导和诱导ADCC活性（抗体依赖性细胞介导的细胞毒性）来降低Her 2阳性肿瘤负荷。在本研究中，我们通过将帕妥珠单抗Fab连接至抗CD 16单结构域抗体来产生双特异性抗体Her 2（Per）-S-Fab。Her 2（Per）-S-Fab可在大肠杆菌中高效表达和纯化。体内外实验表明，Her 2（Per）-S-Fab对Her 2阳性肿瘤细胞具有较强的细胞毒作用。因此，Her 2（Per）-S-Fab可以提供治疗Her 2阳性癌症患者的替代方案。
Human epidermal growth factor receptor 2 (HER2) is frequently overexpressed and activated in metastatic breast cancers. Monoclonal antibodies targeting Her2, such as trastuzumab and pertuzumab, have become important targeted therapies for patients with HER2-positive breast cancer. Both trastuzumab and pertuzumab can reduce Her2 positive tumor burden by inhibiting Her2 signaling and inducing ADCC activities (antibody dependent cell-mediated cytotoxicity). In this study, we have generated a bispecific antibody, Her2(Per)-S-Fab, by linking the pertuzumab Fab to an anti-CD16 single domain antibody. The Her2(Per)-S-Fab can be expressed and purified efficiently from Escherichia coli. In vitro and in vivo experiments showed Her2(Per)-S-Fab had potent cytotoxicity against Her2-positive tumor cells. Thus, Her2(Per)-S-Fab may provide an alternative to treat Her2-positive cancer patients.