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Escherichia coli coculture for making bispecific antibodies

An E. coli coculture method could be used to make bispecific antibodies. Cocultures of two different E. coli cell types expressing an anti-c-Met proto-oncogene (MET; HGFR) half-antibody with a 'hole' modification at the heterodimerization interface or an anti-epidermal growth factor receptor (EGFR) half-antibody with a 'knob' modification at the heterodimerization interface were harvested and lysed. In the lysate, the half-antibodies spontaneously assembled into a bispecific antibody. In EGFR-driven, MET-driven or MET-EGFR co-dependent xenograft mouse models, the purified bispecific antibody decreased tumor volume compared with vehicle. The coculture method was used to generate 27 additional bispecific antibodies. Next steps include optimizing coculture and purification methods to increase antibody titers and identifying new target combinations.

SciBX 6(30); doi:10.1038/scibx.2013.807
Published online Aug. 8, 2013

Patent and licensing status undisclosed

Spiess, C. et al. Nat. Biotechnol.; published online July 7, 2013;
Contact: Justin M. Scheer, Genentech Inc., South San Francisco, Calif.
Contact: Christoph Spiess,
same affiliation as above