Challenges to production of antibodies in bacteria and yeast.

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.