Effective small-scale production of antibodies

Using a CELLine 350 cell culture system, supplied by INTEGRA Biosciences AG, the Institute for Molecular Medicine & Experimental Immunology (IMMEI) (Bonn, Germany) has transformed the effectiveness of its small-scale antibody production.

Designed for ease-of-use the CELLine 350 utilises proprietary membrane technology to separate off the cultivation chamber with an upper semi-permeable membrane through which nutrient can diffuse and a lower one that allows gases to diffuse. Separate ports allow selective access to the upper nutrient supply chamber and the central cultivation chamber. This novel compartmentalised arrangement means that medium can be exchanged without influencing the function or growth of the cells and gases. Consequently, traditional cell growth limitations brought about by a lack of nutrients or the accumulation of metabolic waste can be overcome just as easily as oxygen deficiency. Such optimised conditions promote significant cell growth and lead to drastically increased cell densities.

Petra Peters a technical assistant at IMMEI stated "For about two years I've been working with Hybridoma cells to produce antibodies and for the last year I have been using the Integra Biosciences CELLine 350 to do this work. I've become enthusiastic about this type of cell cultivation because working with CELLine 350 is very time efficient and cost-saving. A colleague called my attention to this cell culture flask and initially I was quite sceptical regarding its stated benefits relating to growth, cell proliferation and especially antibody production. My doubts disappeared a week later, when I saw that my cells had happily multiplied, even in that tiny volume of medium and bit of foetal calf serum I had added. Today I have mastered cell cultivation using the CELLine 350 to such an extent that I can produce large amounts of antibody in a very short time. My CELLine flasks are in use for months in a row and I've even succeeded in storing a used flask for several months at 4°C and then reusing it for cultivating the cells originally grown with that flask. I'm enthusiastic about and can strongly recommend the Integra CELLine flasks for antibody production."

Cells growing under the optimal conditions created in CELLine reach densities of 107 to 108 cells per ml and the concentration of expressed protein is typically 50 to 100 times above what is found in standard cell culture disposables. By combining high product concentration with recurring product collection, large amounts of highly concentrated proteins are routinely obtained in CELLine. In the case of monoclonal antibodies (MAb), average concentrations range from 1 to 2 mg/ml of MAb (in both CELLine 350 and the larger CELLine 1000) and monthly yields typically range from 100 to 250 mg (using a CELLine 1000).

The CELLine has been designed to bring considerable cost savings to cell cultivation. The novel bioreactor drastically reduces the need for high capital investments in cell culture instrumentation or handling large amounts of cell culture disposables in order to be able to obtain milligram amounts of a designated protein. High production yields together with a 90% reduction in media supplement requirements enable further cost and time-savings in downstream processing steps.