Effective suppression of breast tumor growth by an anti-EGFR/ErbB2 bispecific antibody.
Effective suppression of breast tumor growth by an anti-EGFR/ErbB2 bispecific antibody.
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DOI：
10.1016/j.canlet.2012.07.007
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发表时间：
2012-12
期刊：
影响因子：
9.7
通讯作者：
Shuhui Wang;Changchun Chen;Yanchun Meng;Shi Hu;Lei Zheng;Jinjing Song;Da-peng Zhang;Bo-hua Li;Ya-jun Guo
中科院分区：
文献类型：
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作者：
Shuhui Wang;Changchun Chen;Yanchun Meng;Shi Hu;Lei Zheng;Jinjing Song;Da-peng Zhang;Bo-hua Li;Ya-jun Guo
尽管抗ErbB 2人源化抗体曲妥珠单抗有效，但只有不到35%的ErbB 2过表达乳腺癌患者对治疗有反应。在这里，我们使用曲妥珠单抗和西妥昔单抗（一种抗EGFR嵌合抗体）设计了一种抗EGFR/ErbB 2双特异性抗体（TC-BsAb）。TC-BsAb治疗导致EGFR和ErbB 2的内化，而曲妥珠单抗和西妥昔单抗，无论是单独或组合，未能诱导ErbB 2内化。体外和体内实验均表明，TC-BsAb在抑制乳腺癌细胞系生长方面比曲妥珠单抗、西妥昔单抗和曲妥珠单抗加西妥昔单抗更有效，表明其在治疗乳腺癌方面的潜在用途。
Despite the effectiveness of the anti-ErbB2 humanized antibody trastuzumab, less than 35% of patients with ErbB2-overexpressing breast cancer respond to the treatment. Here we engineered an anti-EGFR/ErbB2 bispecific antibody (TC-BsAb) using trastuzumab and cetuximab, an anti-EGFR chimeric antibody. TC-BsAb treatment led to internalization of both EGFR and ErbB2, whereas trastuzumab and cetuximab, either alone or in combination, failed to induce ErbB2 internalization. Both in vitro and in vivo experiments indicated that TC-BsAb was significantly more potent in inhibiting the growth of breast cancer cell lines than trastuzumab, cetuximab, and trastuzumab plus cetuximab, suggesting its potential use for treating breast cancer.