The Stability You Need, the Innovation You Deserve
Lonza has developed a highly efficient mammalian expression system which makes use of selection, via glutamine metabolism, and powerful viral promoters. The GS System™ is well established with over 100 companies using the technology worldwide. Currently there are over 100 products in clinical trials and 10 products in-market that use the GS System™.
The high manufacturing cost of protein products means that maximizing volumetric productivity is essential. Use of the GS System™ reliably results in high-producing cell lines early in cell line construction programs. Maximum expression levels often depend on the product, but at Lonza we have created cell lines producing over 9.6 g/L of recombinant antibody with specific production rates in the range 15-65 pg/cell/day.
Figure 1: Productivity in chemically defined, animal component-free v8 GS-CHO commercial platform process for Lonza’s model antibody cB72.3.
Figure 2: Productivity in chemically defined, animal component-free GS-NS0 bioreactor process
The development stage of any biotechnology project is crucial to success. The GS Expression System™ allows for rapid selection of high-producing cell lines. Product concentrations can be increased further through media and process optimization. This significantly reduces the time required to generate a cell line suitable for cGMP manufacture. Construction of full length antibodies with human constant regions is quick and easy using Lonza’s GS constant region vectors, which enable the addition of any variable region in a single ligation step. Lonza’s proprietary CHOK1SV host cell line is pre-adapted to growth in chemically defined, animal component-free (CDACF) media and suspension culture. It’s pre-adaptation to suspension culture aids adaptation of GS cell lines back to growth in suspension culture after transfection.
Figure 1: Timeline of steps performed to select high-yielding uncloned GS-CHO cell lines adapted to chemically defined, animal component-free media
GS cell lines that are "consistent" in terms of product concentration, growth and product characteristics can be easily created. For unamplified, GS negative cell lines, such as NS0, the selective agent and inhibitor of GS activity methionine sulphoximine is not required for stability. For unamplified, GS positive cell lines, such as CHO, methionine sulphoximine is typically required to maintain volumetric productivity at a consistent level.
For over a 20 years, Lonza has continually advanced the GS Platform. Most recently we have made improvements to the commercial platform process, host cell line and vectors have resulted in the development of our new GS Xceed™ Gene Expression System. The new system produces high product titers in a robust, chemically defined, animal component-free (CDACF) environment and requires no MSX for stability.
The new GS Xceed™ System has shown similar results in both average titer and glycosylation patterns to the existing CHOK1SV cell line.
Figure 1: CHOK1SV and GS-KO Cell lines expressing a model antibody (cB72.3) evaluated in 10 L model of production fed-batch bioreactor, using Lonza's Version 8 Media and Feeds Platform.
Figure 2. Comparability of glycan structure for CHOK1SV GS-KO and CHOK1SV derived cell lines assessed in a shake-flask model of Lonza’s v8 GS-CHO Commercial Platform.
Our mammalian cell culture experts have created hundreds of cell lines in our world renowned GS Gene Expression System™. Many of these cell lines have been grown at large scale and have produced products for use in clinical trials and for in-market supply. Other GS users have accumulated experience with a diverse range of products. In most cases, high harvest product concentrations were achieved. Many investigators use GS, not only to develop a manufacturing process, but as a tool to create recombinant proteins for biological studies. In these cases, the reliability of GS as a consistent means of generating high-producing cell lines quickly, is invaluable.