[Frontiers in Bioscience 4576-4594, May 1, 2008]

Production systems for recombinant antibodies

Thomas Schirrmann, Laila Al-Halabi, Stefan Dubel, Michael Hust

Technische Universitat Braunschweig, Institut fur Biochemie und Biotechnologie, Abteilung Biotechnologie, Spielmannstr. 7., 38106 Braunschweig

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Antibody Production in prokaryotic hosts
3.1. Gram-negative bacteria
3.2. Gram-positive bacteria
4. Antibody Production in Eukaryotic Hosts
4.1. Yeast
4.2. Filamentous fungi
4.3. Insect cells
4.4. Mammalian cells
4.5. Transgenic plants
4.6. Transgenic animals
5. Concluding remarks
6. References

1. 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.