Production of recombinant protein therapeutics in cultivated.pdfVIP

R E V I E W y Production of recombinant protein g o l o n h c therapeutics in cultivated mammalian cells e t o i b e r Florian M Wurm u t a n / m o Cultivated mammalian cells have become the dominant system for the production of recombinant proteins for clinical c . e applications because of their capacity for proper protein folding, assembly and post-translational modification. Thus, the r u t quality and efficacy of a protein can be superior when expressed in mammalian cells versus other hosts such as bacteria, plants a n w. and yeast. Recently, the productivity of mammalian cells cultivated in bioreactors has reached the gram per liter range in a w number of cases, a more than 100-fold yield improvement over titers seen for similar processes in the mid-1980s. This increase w / / in volumetric productivity has resulted mainly from improvements in media composition and process control. Opportunities still : p t exist for improving mammalian cell systems through further advancements in production systems as well as through vector and t h host cell engineering. p u o r G g In 1986 human tissue plasminogen activator (tPA, Activase; Genen- nontransformed cells. In general, for efficient expression of the recom- n i tech, S. San Francisco, CA, USA) became the first therapeutic protein binant protein, it is not important whether the biopharmaceutical- h s from recombinant mammalian cells to obtain market approval. Today encoding gene and selector genes are on the same plasmid or not. i l b about 60–70% of all recombinant protein pharmaceuticals are pro- Following selection, survivors are transferred as single cells to a u P duce