Synthesis of Bispecific Antibodies using Genetically Encoded Unnatural Amino Acids

被引：137

作者：

Kim, Chan Hyuk ^{[2
,3
]}

Axup, Jun Y. ^{[2
,3
]}

Dubrovska, Anna ^{[2
,3
]}

Kazane, Stephanie A. ^{[2
,3
]}

Hutchins, Benjamin A. ^{[2
,3
]}

Wold, Erik D. ^{[2
,3
]}

Smider, Vaughn V. ^{[1
]}

Schultz, Peter G. ^{[2
,3
]}

机构：

[1] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2012年 / 134卷 / 24期

基金：

新加坡国家研究基金会;

关键词：

CANCER-THERAPY; TUMOR-CELLS; T-CELLS; FRAGMENTS; IDENTIFICATION; RESIDUES; CODE; FAB;

D O I：

10.1021/ja303904e

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页码：9918 / 9921

页数：4

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