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Enhancement of antibody production by the addition of Coenzyme-Q10
Authors:Yoshinobu Konno  Motoi Aoki  Masakazu Takagishi  Naoto Sakai  Masamichi Koike  Kaori Wakamatsu  Shinji Hosoi
Affiliation:(1) Present address: Bioprocess Research and Development Laboratories, Kyowa Hakko Kirin Co., Ltd., 100-1 Hagiwara-machi, Takasaki-shi, Gunma 370-0013, Japan;(2) Present address: Kyowa Hakko Kirin Co., Ltd., 1-6-1 Ohte-machi, Chiyoda-ku, Tokyo, Japan;(3) Kyowa Hakko Kirin Co., Ltd., Tokyo Branch, 36-2 Nihonbashi Hakozaki-cho, Chuo-ku, Tokyo, Japan;(4) Present address: BioWa, Inc., Princeton Commerce Center, 20 Emmons Drive, Suite C-10, Princeton, NJ 08540, USA;(5) Present address: Graduate School of Engineering, Gunma University, 1-5-1 Tenjin-cho, Kiryu-shi 376-8515, Japan
Abstract:Recently, there has been a growing demand for therapeutic monoclonal antibodies (MAbs) on the global market. Because therapeutic MAbs are more expensive than low-molecular-weight drugs, there have been strong demands to lower their production costs. Therefore, efficient methods to minimize the cost of goods are currently active areas of research. We have screened several enhancers of specific MAb production rate (SPR) using a YB2/0 cell line and found that coenzyme-Q10 (CoQ10) is a promising enhancer candidate. CoQ10 is well known as a strong antioxidant in the respiratory chain and is used for healthcare and other applications. Because CoQ10 is negligibly water soluble, most studies are limited by low concentrations. We added CoQ10 to a culture medium as dispersed nanoparticles at several concentrations (Q-Media) and conducted a fed-batch culture. Although the Q-Media had no effect on cumulative viable cell density, it enhanced SPR by 29%. In addition, the Q-Media had no effect on the binding or cytotoxic activity of MAbs. Q-Media also enhanced SPR with CHO and NS0 cell lines by 30%. These observations suggest that CoQ10 serves as a powerful aid in the production of MAbs by enhancing SPR without changing the characteristics of cell growth, or adversely affecting the quality or biological activity of MAbs.
Keywords:Antioxidant   Coenzyme-Q10   Chinese hamster ovary (CHO)   8-hydroxy-2′-deoxyguanosine   Monoclonal antibodies   NS0   Specific production rate   YB2/0   Enhancer   Productivity
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