Escherichia coli offers short-cut to large-scale Trimerbody® manufacturing

05-08-2015

Trimerbody® is a unique mono/multispecific antibody format based on the use of specific collagen trimerization domains and optimized peptide linkers. Trimerbodies are trimeric in solution and exhibit excellent antigen binding capacity and stability in vitro and in vivo. Due to their trimeric nature and the requirement of disulfide bonds for the generation of functional antigen-binding sites in the single-chain variable fragment domains (scFv), Trimerbodies have been produced in eukaryotic cell systems, including yeast (Pichia Pastoris) and mammalian cells. However, nearly 30% of currently clinically approved recombinant therapeutic proteins are produced in Escherichia coli (E. coli). The leading reason for this choice is cost-effectiveness as well as the availability of a diverse molecular toolkit for genetic engineering.

Leadartis scientists, in collaboration with academic teams from Spain and Denmark, have demonstrated that E. coli is an effective expression system for scFv-based N-terminal Trimerbodies. Functional and structural analysis of equivalent Trimerbodies produced in E. coli or mammalian cells, demonstrated their comparableness, suggesting that E. coli is a viable manufacturing system for scFv-based N-terminal Trimerbodies.

Conclusions and relevance
Innovations in protein manufacturing have been instrumental in drastically reducing biotherapeutics development timelines and cost with larger scales and higher protein yields being at the forefront of the wishing list to further assisting clinical development. Every manufacturing method poses its own advantages and limitations so having different options becomes critical to the success of a particular developmental program. Further, E. coli-based platforms are tremendously popular among new and established biologics manufacturers consequently offering a viable alternative to shrink developmental workflows by substituting time-intensive steps shortening product and process development timelines.

These findings were reported on August 2015 in AMB Express. (http://www.amb-express.com/content/5/1/45)

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