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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Veröffentlicht in:	Journal of the American Chemical Society 2012-06, Vol.134 (24), p.9918-9921
Hauptverfasser:	Kim, Chan Hyuk, Axup, Jun Y, Dubrovska, Anna, Kazane, Stephanie A, Hutchins, Benjamin A, Wold, Erik D, Smider, Vaughn V, Schultz, Peter G
Format:	Artikel
Sprache:	eng
Schlagworte:	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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Beschreibung
Zusammenfassung:	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