Advances in recombinant antibody manufacturing.

Renate Kunert,David Reinhart

doi:10.1007/s00253-016-7388-9

Abstract

Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.

Highlights

Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances
In the mid-1970s, the foundation for the commercial success of antibodies was laid by Köhler and Milstein who developed the method for immortalization of B lymphocytes for the purpose of monoclonal antibody production (Köhler and Milstein 1975)
The mean specific secretion rate of 3D6scFvFc was more than 1000-fold higher in the CHO cells compared to the P. pastoris strains

Summary

Introduction

Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. Critical parameters in this procedure are (i) the time until a desired cell density is reached, determined by the specific growth rate (μ) of the cells; (ii) the duration of the production phase enabling an accumulation of recombinant protein from a high-density and viable culture; and (iii) the obtainable product titer determined by the specific production rate (qP) and the overall process duration.

Results

Conclusion