Production of Recombinant Therapeutic Proteins in Human Cells: Current Achievements and Future Perspectives

Abstract

Over the past 20 years the demand for recombinant proteins has increased significantly. Mammalian cell lines have been extensively used to produce recombinant proteins. This expression system offers several advantages over microbial systems, mammalian cells have the cellular machinery to promote the secretion of the recombinant product and the posttranslational modifications, like glycosylation that is present in many of recombinant therapeutic proteins in the market. Human cell lines have emerged as a new and powerful alternative for production of such products. These cells are able to produce recombinant proteins with posttranslational modifications more similar to their natural counterparts, producing proteins with human-like glycosylation pattern avoiding immunogenic reactions against epitopes nonhumans. This review presents the available human cell lines that can be used in pharmaceutical industry, the advantages of this expression system and the main efforts made in this field.

Human Embryonic Kidney 293 Cells: A Vehicle for Biopharmaceutical Manufacturing, Structural Biology, and Electrophysiology

“…Recently, a new strategy has been developed in HEK293 cells by the human cytomegalovirus intermediate-early enhancer promoter in combination with the IFNα2 signal peptide to enhance heterologous protein expression and secretion [Román et al, 2016]. Furthermore, numerous protocols using HEK293 cells as host for transient or stable gene expression have been published [Zhao et al, 2011;Picanco-Castro et al, 2013;Hacker and Balasubramanian, 2016]. In addition, the production process of serum-free suspension culture has been gradually improved and perfected [Pham et al, 2003;Subedi et al, 2015;Do Amaral et al, 2016;Grieger et al, 2016].…”

Production of recombinant coagulation factors: Are humans the best host cells?

“…48,49 Xigris Ò , activated protein C, was the first recombinant therapeutic protein produced in Hek293 cells approved by the FDA (2001); however, it was voluntarily withdrawn from market in 2011 by its manufacturer (Eli Lilly). 50 In addition to Hek293 cells, novel human cell lines have been explored for improved recombinant FVIII production. Our research group showed that human hepatic cell lines, such as SK-HEP and HepG2 cells, have already been used for successful expression of rFVIII.…”

Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives

“…, 2003; Durocher & Butler, 2009; Picanco-Castro et al . , 2013). The advantages of this cell line include high-level protein production without the formation of aggregates, which can be a problem in other human cell lines (Picanco-Castro et al .…”

“…The advantages of this cell line include high-level protein production without the formation of aggregates, which can be a problem in other human cell lines (Picanco-Castro et al . , 2013). Notably, HKB-11 has demonstrated increased expression of human FVIII compared with expression in HEK293 and BHK21 (Mei et al .…”

“…Similar to other human cell lines, it has been shown to produce human glycosylation patterns including α (2,3) and α (2,6) sialic acid linkages (Picanco-Castro et al . , 2013). HKB-11 has been used to produce a recombinant factor VIII protein and tissue factor (Cho et al .…”