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. 2013 Aug;31(8):753-8.
doi: 10.1038/nbt.2621. Epub 2013 Jul 7.

Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies

Christoph Spiess  1 , Mark Merchant, Arthur Huang, Zhong Zheng, Nai-Ying Yang, Jing Peng, Diego Ellerman, Whitney Shatz, Dorothea Reilly, Daniel G Yansura, Justin M Scheer
Affiliations

Bispecific antibodies with natural architecture produced by co-culture of bacteria expressing two distinct half-antibodies

Christoph Spiess et al. Nat Biotechnol. 2013 Aug.

Abstract

By enabling the simultaneous engagement of two distinct _targets, bispecific antibodies broaden the potential utility of antibody-based therapies. However, bispecific-antibody design and production remain challenging, owing to the need to incorporate two distinct heavy and light chain pairs while maintaining natural nonimmunogenic antibody architecture. Here we present a bispecific-antibody production strategy that relies on co-culture of two bacterial strains, each expressing a half-antibody. Using this approach, we produce 28 unique bispecific antibodies. A bispecific antibody against the receptor tyrosine kinases MET and EGFR binds both _targets monovalently, inhibits their signaling, and suppresses MET and EGFR-driven cell and tumor growth. Our strategy allows rapid generation of bispecific antibodies from any two existing antibodies and yields milligram to gram quantities of bispecific antibodies sufficient for a wide range of discovery and preclinical applications.

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