Synthesis of Bispecific Antibodies using Genetically Encoded Unnatural Amino Acids

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-link...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2012-06, Vol.134 (24), p.9918-9921
Main Authors: Kim, Chan Hyuk, Axup, Jun Y, Dubrovska, Anna, Kazane, Stephanie A, Hutchins, Benjamin A, Wold, Erik D, Smider, Vaughn V, Schultz, Peter G
Format: Article
Language:English
Subjects:
amino acids
Amino Acids - chemistry
antibodies
Antibodies, Bispecific - chemistry
Antibodies, Bispecific - immunology
CD3 Complex - immunology
Cell Line
Cell Line, Tumor
crosslinking
cytotoxicity
Cytotoxicity, Immunologic
Humans
Models, Molecular
Receptor, ErbB-2 - immunology
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Summary: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.
ISSN:0002-7863
1520-5126
1520-5126
DOI:10.1021/ja303904e