title: Impact of hydrolysates on monoclonal antibody productivity, purification and quality in Chinese hamster ovary cells.
abstract: Plant and yeast derived hydrolysates are economical and efficient alternative medium supplements to improve mammalian cell culture performance. We supplemented two commercial Chinese hamster ovary (CHO) culture media with hydrolysates from four different sources, yeast, soybean, Ex-Cell CD (a chemically defined hydrolysate replacement) and wheat to improve the productivity of two cell lines expressing different monoclonal antibodies (mAbs). Yeast, soybean and Ex-Cell CD improved the final mAb titer by increasing the specific productivity (qP) and/or extension of the culture period. Wheat hydrolysates increased peak viable cell density but did not improve productivity. IgG recovery from protein A purification was not compromised for all cultures by adding yeast, soybean and Ex-Cell CD hydrolysates except for one sample from soybean supplemented culture. Adding these three hydrolysates neither increased the amount of host cell protein, DNA or aggregate impurity amounts nor affect their clearance after purification. Profiling of the glycan types revealed that yeast and soybean hydrolysates could affect the distribution of galactosylated glycans. Ex-Cell CD performed the best at maintaining glycan profile compared to the non-supplemented cultures. Overall, yeast performed the best at improving CHO culture growth and productivity without being detrimental to downstream protein A processes but could affect mAb product glycan distribution while Ex-Cell CD yielded lower titers but has less effect on glycosylation. The hydrolysate to use would thus depend on the requirements of each process and our results would provide a good reference for improving culture performance with hydrolysates or related studies.
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668, Singapore.
authors.forename: Steven C L
authors.initials: SC
authors.lastname: Ho
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668, Singapore.
authors.forename: Rui
authors.initials: R
authors.lastname: Nian
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668, Singapore.
authors.forename: Susanto
authors.initials: S
authors.lastname: Woen
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668, Singapore.
authors.forename: Jake
authors.initials: J
authors.lastname: Chng
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668, Singapore.
authors.forename: Peiqing
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, 138668, Singapore. Electronic address: yang_yuansheng@bti.a-star.edu.sg.
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D016466:CHO Cells; D002452:Cell Count; D018929:Cell Culture Techniques / Q000379:methods*; D002457:Cell Extracts / Q000494:pharmacology*; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology*; D006031:Glycosylation / Q000187:drug effects; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D011134:Polysaccharides / Q000032:analysis; D013025:Glycine max / Q000737:chemistry; D013205:Staphylococcal Protein A; D014908:Triticum; D015003:Yeasts / Q000737:chemistry
chemical_list: D000911:Antibodies, Monoclonal; D002457:Cell Extracts; D003470:Culture Media; D007074:Immunoglobulin G; D011134:Polysaccharides; D013205:Staphylococcal Protein A
keywords: Aggregation; Chinese hamster ovary; Glycosylation; Host cell protein; Hydrolysates; Monoclonal antibody; Productivity; Purification