Novel cell line development strategy for monoclonal antibody manufacturing using translational enhancing technology

Kenji Masuda, Kazuhiko Watanabe, Tomonori Ueno, Yuto Nakazawa, Yumiko Tanabe, Yuko Ushiki-Kaku, Kiyoko Ogawa-Goto, Yukikazu Ehara, Hisashi Saeki, Takeshi Okumura, Koichi Nonaka, Masamichi Kamihira

研究成果: ジャーナルへの寄稿学術誌査読

5 被引用数 (Scopus)

抄録

Chinese hamster ovary (CHO) cells are widely used for constructing expression systems to produce therapeutic proteins. However, the establishment of high-producer clones remains a laborious and time-consuming process, despite various progresses having been made in cell line development. We previously developed a new strategy for screening high monoclonal antibody (mAb)-producing cells using flow cytometry (FCM). We also reported that p180 and SF3b4 play key roles in active translation on the endoplasmic reticulum, and that the productivity of secreted alkaline phosphatase was enhanced by the overexpression of p180 and SF3b4. Here, we attempted to apply the translational enhancing technology to high mAb-producing cells obtained after high-producer cell sorting. A high mAb-producing CHO clone, L003, which showed an mAb production level of >3 g/L in fed-batch culture, was established from a high mAb-producing cell pool fractionated by FCM. Clones generated by the overexpression of p180 and SF3b4 in L003 cells were evaluated by fed-batch culture. The specific productivity of clones overexpressing these two factors was ∼3.1-fold higher than that of parental L003 cells in the early phase of the culture period. Furthermore, the final mAb concentration was increased to 9.5 g/L during 17 days of fed-batch culture after optimizing the medium and culture process. These results indicate that the overexpression of p180 and SF3b4 would be promising for establishing high-producer cell lines applicable to industrial production.

本文言語英語
ページ(範囲)273-280
ページ数8
ジャーナルJournal of Bioscience and Bioengineering
133
3
DOI
出版ステータス出版済み - 3月 2022

!!!All Science Journal Classification (ASJC) codes

  • バイオテクノロジー
  • バイオエンジニアリング
  • 応用微生物学とバイオテクノロジー

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