S5: Bispecific Antibody Production in E. coli: Half the Story

Humanized monospecific antibodies are convenient therapeutics when the antigen is a well defined single target; however many disease states are complex and may require targeting more than one antigen at the same time.  Thus, bispecific antibodies (bsAbs) are being developed by companies in an attempt to target two different cell surface receptors, two different soluble antigens or to elicit T-cell mediated killing of cancer cells.

In the literature there are a multitude of bsAbs in development that range in valency and format from bivalent diabodies to tetravalent dual-variable-domain antibodies (DVD-Ig). At Genentech one approach for the generation of bivalent bsAbs is the production of intact half antibodies (hAbs) in separate E. coli fermentations.

The production of hAbs in E. coli requires the optimization of a number of cellular processes within two distinct compartments (cytoplasm and periplasm) and across a single membrane (inner membrane). Over the past decade a number of technologies have been tested and implemented at Genentech that aid in the production of antibodies in E. coli. This talk will discuss some of our recent work in this area.