Comparison of Bioreactors for the Produciton of hCTLA4Ig in Transgenic Rice Cell Cultures

초록

Biopharmaceuticals are the fastest growing segment of pharmaceutical industry. Plant cell-based manufacturing system is being studied as a potentially cheap, safe, and scalable alternative to mammalian and bacterial production of biopharmaceuticals, including biosimilars for patent-expiring protein drugs1). However, the slow cell growth and low product yields are the main drawback for industrial application of plant cell cultures. Studies on distinctive features of different bioreactor types are required to optimize production processes by choosing the most suitable bioreactor type for the cultures2). Air-lift bioreactor and stirred-tank bioreactor, the most widely used types of the bioreactor for plant cell cultures, are compared in this study. Transgenic suspension cells of Oryza sativa, which were utilized as a host for producing recombinant human cytotoxic T lymphocyte-associated antigen 4-immunoglobulin (hCTLA4Ig), were cultured in the two types of 5-L bioreactors. A fed-batch culture method was used for the efficient production of hCTLA4Ig with concentrated amino acids feeding3). Dissolved oxygen level was regulated at 30% by adding pure oxygen with solenoid valve during the run. The results of the comparison between air-lift bioreactor and stirred-tank bioreactor show that 1.1-fold higher maximum cell density reaching 12.9 g/L at day 10 with stirred-tank bioreactor due to better mixing during the culture. However, the maximum production level of hCTLA4Ig was 1.35-fold higher (18.2 mg/L) at day 24 with air-lift bioreactor compared to that with stirred-tank bioreactor. It is presumed that mechanical agitation induces cell lysis with the excretion of intracellular protease