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Synthesis of Bispecific Antibodies using Genetically Encoded Unnatural Amino Acids

2012; American Chemical Society; Volume: 134; Issue: 24 Linguagem: Inglês

10.1021/ja303904e

1943-2984

Chan Hyuk Kim, Jun Y. Axup, Anna Dubrovska, Stephanie A. Kazane, Benjamin A. Hutchins, Erik D. Wold, Vaughn V. Smider, Peter G. Schultz,

HER2/EGFR in Cancer Research

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.