Production systems for recombinant antibodies

Abstract

Recombinant antibodies are the fastest growing class of therapeutic proteins. Furthermore, antibodies are key detection reagents in research and diagnostics. The increasing demand for antibodies with regards to amount and quality resulted in the development of a variety of recombinant production systems employing gram-negative and gram-positive bacteria, yeast and filamentous fungi, insect cell lines as well as mammalian cell lines. More recently, antibodies were also successfully produced in transgenic plants and animals. Currently, the production of recombinant antibodies for therapy is performed in mammalian cell lines to reduce the risk of immunogenicity caused by non-human post-translational modifications, in particular glycosylation. However, novel strategies already allow human-like glycosylation patterns in yeast, insect cell lines and transgenic plants. Furthermore, therapeutic strategies not requiring glycosylation of the Fc portion have been conceived, most prominently using bispecific antibodies or scFv fusion proteins, which can be produced in bacteria. Here, we review all current antibody production systems considering their advantages and limitations with respect to intended applications.

Development of Human and Macaque Antibodies Using Antibody Phage Display for the Detection of Equine Encephalitis Viruses

“…Because the gene sequence of the binder is available, the antibody -depending on the desired application -can be converted into different antibody formats (e.g. scFv-Fc fusion or IgG) and produced in different production hosts Schirrmann et al, 2008). In summary, recombinant antibody fragments derived from phage display can be adapted to the final assay requirements.…”

Establishment of Stable Chinese Hamster Ovary Cell Line Capable of Expressing Human Recombinant Hemopexin: A Promising Therapeutic Modality Against Hemolytic Anemia

“…Thus, mammalian cell lines, particularly Chinese hamster ovary (CHO) cells (18), are generally harnessed as an efficient expression host due to the human-compatible glycosylation machinery to efficiently fold and secrete this glycoprotein (19).…”

Specific detection and quantitation of bovine IgG in bioreactor derived mouse mAb preparations

“…In the past decades, monoclonal antibody (mAb) production and application as research and diagnostic tools or as therapeutic agents for various human diseases has created a great deal of interest, which is constantly on the rise (Hagemeyer et al 2009;Siddiqui 2010;Guergova-Kuras et al 2011;Modjtahedi et al 2012;Elvin et al 2013). Apart from their recombinant forms which are generated in high producer CHO or other type of cells, most of the antibodies are produced using hybridomas, either in animals (in vivo) or in cell culture (in vitro) (Schirrmann et al 2008;Liu 2014). In vivo antibody manufacturing has been a widespread method of mAb production because of its reliability, high antibody yield and cost effectiveness (Jackson et al 1996;Peterson and Peavey 1998).…”