Initial development of biosimilar immune checkpoint blockers using HEK293 cells

Ramos, Michael Bernardes; Araújo, Anna Érika Vieira de; Pestana, Cristiane Pinheiro; Bom, Ana Paula Dinis Ano; Bastos, Renata Chagas; Oliveira, Aline de Almeida; Neves, Patrícia Cristina da Costa; Silva, Haroldo Cid da

doi:10.1016/j.pep.2020.105596

Cited by 1 publication

(1 citation statement)

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“…The CHO cell lines, epithelial cells derived from the ovary of the Chinese hamster, have been the predominant mammalian line in the biotechnology industry, particularly for glycoprotein production ( Lalonde and Durocher, 2017 ). However, these cell lines can introduce immunogenic structures that negatively impact the efficacy of some biopharmaceutical products [see, for example, ( Seth et al, 2006 ; Dietmair et al, 2012 ; Kantardjieff and Zhou, 2014 ; Phillips, 2014 ; Ramos et al, 2020 )]. As a result, there has been a growing interest within the industry in utilizing human cell lines, such as HEK293 for the production of recombinant proteins.…”

Section: Introductionmentioning

confidence: 99%

Sodium acetate increases the productivity of HEK293 cells expressing the ECD-Her1 protein in batch cultures: experimental results and metabolic flux analysis

Pérez-Fernández,

Calzadilla,

Enrico Bena

et al. 2024

Front. Bioeng. Biotechnol.

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Human Embryonic Kidney cells (HEK293) are a popular host for recombinant protein expression and production in the biotechnological industry. This has driven within both, the scientific and the engineering communities, the search for strategies to increase their protein productivity. The present work is inserted into this search exploring the impact of adding sodium acetate (NaAc) into a batch culture of HEK293 cells. We monitored, as a function of time, the cell density, many external metabolites, and the supernatant concentration of the heterologous extra-cellular domain ECD-Her1 protein, a protein used to produce a candidate prostate cancer vaccine. We observed that by adding different concentrations of NaAc (0, 4, 6 and 8 mM), the production of ECD-Her1 protein increases consistently with increasing concentration, whereas the carrying capacity of the medium decreases. To understand these results we exploited a combination of experimental and computational techniques. Metabolic Flux Analysis (MFA) was used to infer intracellular metabolic fluxes from the concentration of external metabolites. Moreover, we measured independently the extracellular acidification rate and oxygen consumption rate of the cells. Both approaches support the idea that the addition of NaAc to the culture has a significant impact on the metabolism of the HEK293 cells and that, if properly tuned, enhances the productivity of the heterologous ECD-Her1 protein.

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