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Self-assembled antibody multimers through peptide nucleic acid conjugation.

ABSTRACT: With the recent clinical success of bispecific antibodies, a strategy to rapidly synthesize and evaluate bispecific or higher order multispecific molecules could facilitate the discovery of new therapeutic agents. Here, we show that unnatural amino acids (UAAs) with orthogonal chemical reactivity can be used to generate site-specific antibody-oligonucleotide conjugates. These constructs can then be self-assembled into multimeric complexes with defined composition, valency, and geometry. With this approach, we generated potent bispecific antibodies that recruit cytotoxic T lymphocytes to Her2 and CD20 positive cancer cells, as well as multimeric antibody fragments with enhanced activity. This strategy should accelerate the synthesis and in vitro characterization of antibody constructs with unique specificities and molecular architectures.

SUBMITTER: Kazane SA

PROVIDER: S-EPMC3951380 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Self-assembled antibody multimers through peptide nucleic acid conjugation.

Kazane Stephanie A SA Axup Jun Y JY Kim Chan Hyuk CH Ciobanu Mihai M Wold Erik D ED Barluenga Sofia S Hutchins Benjamin A BA Schultz Peter G PG Winssinger Nicolas N Smider Vaughn V VV

Journal of the American Chemical Society 20121221 1

With the recent clinical success of bispecific antibodies, a strategy to rapidly synthesize and evaluate bispecific or higher order multispecific molecules could facilitate the discovery of new therapeutic agents. Here, we show that unnatural amino acids (UAAs) with orthogonal chemical reactivity can be used to generate site-specific antibody-oligonucleotide conjugates. These constructs can then be self-assembled into multimeric complexes with defined composition, valency, and geometry. With thi ...[more]

PMID: 23210862

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