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Effect of vitamins and metal ions on productivity and charge heterogeneity of IgG1 expressed in CHO cells
Author(s) -
Gangwar Neelesh,
Mishra Rishabh,
Budholiya Niharika,
Rathore Anurag S.
Publication year - 2021
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.202000464
Subject(s) - chinese hamster ovary cell , biotin , chemistry , pyridoxine , glycosylation , biochemistry , vitamin , pyridoxine hydrochloride , receptor
Recombinant monoclonal antibodies have emerged as the most successful modality of biotherapeutics. They are primarily expressed in Chinese Hamster Ovary (CHO) cells. It is well known that post‐translational modifications (PTM) contribute significantly to heterogeneity with respect to charge, glycosylation, and size. These attributes in turn impact stability, pharmacokinetics, and pharmacodynamics of the biotherapeutic product. Cell culture media components are known to significantly contribute to both cellular productivity as well as post‐translational modifications. Thus, it is highly desirable to understand how media components affect product quality. This study aims to explore the impact of vitamins and metal ions on protein expression and post‐translational modifications specifically charge heterogeneity. Biotin, choline chloride, D‐calcium pantothenate, folic acid, pyridoxine hydrochloride, thiamine hydrochloride vitamins and Fe, Cu, Mg, Co, Zn, Mn, Ni metal ions were examined in this study. The results indicate that pyridoxine enhances productivity while Zn, Cu, Fe, Mn, and biotin impact charge heterogeneity. While, Fe, Mn and Ni enhance production of the acidic variants, Cu and biotin inhibit it. Zn reduces formation of basic variants while biotin enhances it. The results from this investigation could be used for process control so as to get consistent charge variant profile, in particular for biosimilars.