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Synthesis of bispecific antibodies using genetically encoded unnatural amino acids.


ABSTRACT: 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.

SUBMITTER: Kim CH 

PROVIDER: S-EPMC4299457 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

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Synthesis of bispecific antibodies using genetically encoded unnatural amino acids.

Kim Chan Hyuk CH   Axup Jun Y JY   Dubrovska Anna A   Kazane Stephanie A SA   Hutchins Benjamin A BA   Wold Erik D ED   Smider Vaughn V VV   Schultz Peter G PG  

Journal of the American Chemical Society 20120606 24


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. ...[more]

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