Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
J Am Chem Soc. 2012 Jun 20;134(24):9918-21. doi: 10.1021/ja303904e. Epub 2012 Jun 6.
Bispecific antibodies were constructed using genetically encoded unnatural amino acids with orthogonal chemical reactivity. A two-step process afforded homogeneous products in excellent yield. Using this approach, we synthesized an anti-HER2/anti-CD3 bispecific antibody, which efficiently cross-linked HER2+ cells and CD3+ cells. In vitro effector-cell mediated cytotoxicity was observed at picomolar concentrations.
双特异性抗体是使用具有正交化学反应性的遗传编码非天然氨基酸构建的。两步法以优异的收率得到均相产物。使用这种方法，我们合成了一种抗 HER2/抗 CD3 双特异性抗体，它能有效地交联 HER2+细胞和 CD3+细胞。在皮摩尔浓度下观察到体外效应细胞介导的细胞毒性。
