Efficient antibody production with suppressing O-Glycosylation in yeast

BIOT 84

Kazuo Kobayashi, kkobayashi@kirin.co.jp1, Kousuke Kuroda, Kousuke_Kuroda@kirin.co.jp1, Haruhiko Tsumura, htsumura@kirin.co.jp1, Toshihiro Komeda, t-komeda@kirin.co.jp2, Yasunori Chiba, y-chiba@aist.go.jp3, Yoshihumi Jigami, jigami.yoshi@aist.go.jp3, Kimihisa Ichikawa, yichik@sankyo.co.jp4, Koichi Nonaka, nonaka@sankyo.co.jp5, and Takeshi Suzuki, suzuki_takeshi@sankyo.co.jp5. (1) CMC R&D Laboratories, Kirin Brewery Co., Ltd, 100-1, Hagiwara-machi, Takasaki-shi, Gunma, 370-0013, Japan, (2) 2, Central Laboratories for Frontier Technology, Kirin Brewery Co., Ltd, 3, Miyahara-cho, Takasaki-shi, Gunma, 370-0004, Japan, (3) Cell Engineering Department, National Institute Advanced Industrial Science and Technology, 1-1-1, Higashi, Tukuba-chi, Ibaraki, 305-8566, Japan, (4) Core Technology Research Laboratories, Sankyo Co., Ltd, 1-2-58, Hiro-machi, Shinagawa-ku, Tokyo, 140-8710, Japan, (5) Process Development Laboratories, Sankyo Co., Ltd, 389-4, Aza-otsurugi, Shimokawa, Izumi-mashi, Iwaki-shi, Fukushima, 971-8183, Japan
Antibodies for pharmaceuticals are produced by mammalian cells as conventional host. However several approaches have been investigated to reduce the cost of production by mammalian cells, little method is proposed to overcome the problem. When antibody was produced in fungi, abnormal O-glycosylation (mannosylation) was detected in secreted antibody. This modification was catalyzed by protein-O-mannosyltransferases (Pmtps) which localize in endoplasmic reticulum (ER) but not Golgi apparatus in mammalian cells. Because O-linked sugar chains might have immunogenicity against human, reduce stability and binding to antigens and Fc receptors, it is necessary to produce the antibody without the O-linked sugar chains for pharmaceuticals in yeast. In this study, we have examined to suppress the O-glycosylation in the antibody and developed a novel system for antibody production using methylotrophic yeast O. minuta.
 

Upstream Processing: Advances in Microbial Fermentation Process Development
8:00 AM-10:15 AM, Monday, August 20, 2007 BCEC -- 106, Oral

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007