Thursday, August 8, 2013
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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.
Published online Aug. 8, 2013
Patent and licensing status
Spiess, C. et al. Nat.
Biotechnol.; published online July 7, 2013;
Contact: Justin M. Scheer, Genentech Inc., South San
Contact: Christoph Spiess,
same affiliation as above
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