Vivalis cell lines show MAb production power

By Anna Lewcock

- Last updated on GMT

Related tags: Biotechnology, Immune system, Cell culture

French firm Vivalis has announced the first data evaluating its
proprietary EBx cell lines for the production of monoclonal
antibodies (MAbs), with initial results suggesting high cytotoxic
properties in the resultant MAbs.

The antibodies produced using the EBx cell lines showed remarkably low fucose content - a key point in favour of the production method as reduced fucose content is known to be associated with improved antibody-dependent cell cytotoxicity (ADCC) activity, particularly important in treating cancerous cells. Vivalis has been working in collaboration with another French firm, Mat Biopharma, to evaluate its EBx cell lines for the production of Mat Biopharma's monoclonal antibodies. The companies demonstrated that as well as the reduced fucose content, the glycosylation profile of monoclonal antibody of IgG1 subtype produced in the avian EBx cells was similar to human antibody glycosylation profiles. Already having generated a great deal of industry interest for its potential applications in vaccine manufacture, this is the first data showing that Vivalis' EBx cell lines could prove an attractive alternative to traditional Chinese Hamster Ovary (CHO) cell lines in MAb production. The company developed a proprietary process allowing it to generate cell lines from avian embryonic stem (ES) cells without any genetic, chemical or physical modifications, and applied this process to generate duck cell lines known as EBx. "These duck EBx cells continue to display some striking ES features, like telomerase expression and expression in ES cell markers, but in addition display industrial features like growth in suspension in animal serum-free medium up to high cell densities,"​ Franck Grimaud, Vivalis CEO, told in-PharmaTechnologist.com. "The telomerase expression constitutes a key feature because it is responsible for the genetic stability of EBx cells (they are diploid) and the continuous cell growth (they are immortal); these two characteristics render Vivalis EBx cells unique, because cell line immortality is usually associated with genetic instability like in cancer cells or in continuous cell lines that are transformed." ​ Vivalis demonstrated that it was possible to genetically engineer the EBx cells using well-known transfection methods, with the cells able to be transiently or stably modified with an expression vector encoding the antibody gene sequences of interest. Once the genetic modification is complete, the cell clones that are seen to express the most antibody can then be selected for further development. According to Vivalis, the EBx suspension cells can be efficiently produced in stirred-tank bioreactors, with production times and costs similar to traditional MAb production methods in CHO cell lines. These latest results open up a new market to Vivalis, adding to its already strong position in the vaccine market. With the added bonus of the reduced fucose content in the MAbs giving the platform an edge in the market, Vivalis is justified in its high hopes for this application of its EBx cell lines. "There is a clear need for more potent antibodies, to decrease the amount of antibodies injected to patients, to decrease side effects, but also to decrease costs associated with antibody treatment which constitute a serious drawback,"​ said Grimaud. "This constitutes a real competitive over CHO cells for antibody production." ​ The monoclonal antibody market is currently worth around $20bn according to Vivalis, with approximately 50 per cent of marketed monoclonal antibodies targeting cancers with their cytotoxic properties. Grimaud was reluctant to estimate just how much of the market the company could potentially capture through the use of its EBx cell lines, though the firm did say that it has recently signed collaboration agreements with two other companies looking to evaluate the cellular platform for production of antibodies with increased ADCC activity. Although time scales are currently largely dictated by the company's project partner, Grimaud anticipates the first EBx commercial licence for antibody production by 2009. The next step will be for Vivalis and Mat Biopharma to go ahead and produce the first pre-clinical batch of antibodies using the EBx cell line.

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