Review
Challenges to production of antibodies in bacteria and yeast

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Currently, antibodies play major role in treating a wide variety of human diseases (e.g., cancer, viral infection, inflammation). Those pharmaceutic antibodies have become major therapeutic reagents in the pharmaceutical drug market. In addition to full-length antibodies, the market of antibody fragments, which offer potential advantages in clinical use as well as diagnostics, is gradually growing. As the demand for antibody therapeutics increase, the development of host systems for enhanced, and less expensive, production has also become more important. All therapeutic antibodies approved to date are predominantly produced in mammalian hosts, but due to drawbacks such as high production cost and long-term cultivation, the alternative use of bacteria and yeasts has been seriously considered. Recently, there have been reports of substantial progress in genetic engineering and systems biotechnology, results in development of potential hosts that overcame the critical limitations in bacterial and yeast cells, and much enhanced productivity of functional antibodies. In this review, we highlight recent, significant progress made in the engineering of bacterial and yeast cells for enhanced production of functional antibodies.

Section snippets

Antibody production in bacteria

Bacteria are very attractive for use in recombinant protein production because of their fast growth, ease of manipulation, relatively well-known information and much lower antibody production costs. A number of bacterial hosts (e.g., E. coli, Corynebacterium glutamicum, Bacillus megaterium, Pseudomonas putida) have been utilized for recombinant protein productions (7), and the recent progress made in the production of various antibodies using those bacterial hosts is summarized in Table 1.

Antibody production in yeast

Antibodies originate in the immune cells of animals, thus eukaryotic hosts are preferable for producing recombinant antibodies than prokaryotes. Yeast is a eukaryotic host, but has also several beneficial properties that are comparable to prokaryotic microbial hosts (e.g., fast growth, ease of genetic manipulation, low cultivation cost). In addition, the presence of its own glycosylation machinery makes yeast more attractive than prokaryotes for the production of functional antibodies, despite

CONCLUSIONS AND FURTHER PERSPECTIVE

As of 2014, 32 antibodies are being marketed, and more than 200 antibodies are being evaluated in clinical studies. Given this explosive growth of therapeutic antibodies, the finding of new antibodies is no longer an extraordinary issue in most of the cases. Rather, the development of processes for their economic production is becoming an ever more important issue. Although there have been many successful achievements in engineering of bacterial and yeast hosts as described above, the drive to

Acknowledgments

Ki Jun Jeong expresses his appreciation to the Society for Biotechnology, Japan, which awarded him the Young Asian Biotechnologist Prize in 2014. This research was supported by the Intelligent Synthetic Biology Center of Global Frontier Project (Grant no. 2014M3A6A8066443) funded by the Ministry of Science, ICT, and Future Planning (MISP).

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