Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies

Malphettes, Laetitia; Mathy, Gregory; Gimenez, Laura

doi:10.1186/s12919-018-0097-x

Cited by 2 publications

(4 citation statements)

References 153 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, a nonsynchronized mechanistic model without cell-cycle effects was used to predict the needed concentrations of glucose and glutamine in the feed (Möller, Steinmetz, Braakmann & Pörtner, 2018).…”

Section: Synchronized Cultivationmentioning

confidence: 99%

Model‐based identification of cell‐cycle‐dependent metabolism and putative autocrine effects in antibody producing CHO cell culture

Möller

Korte

Pörtner

et al. 2018

Biotech & Bioengineering

View full text Add to dashboard Cite

The understanding of cell-cycle-dependent population heterogeneities in mammalian cell culture and their influence on production rates is still limited. Furthermore, metabolic regulations arising from self-expressed signaling factors (autocrine/autoinhibitory factors) have been postulated in the past, but no determination of such effects have been made so far for fast-growing production Chinese hamster ovary (CHO) cells in chemically defined media. In this study, a novel approach combining near-physiological treatment of cells (including synchronization), population resolved mechanistic modeling and statistical analysis was developed to identify population inhomogeneities. Cell-cycle-dependent population dynamics and metabolic regulations due to a putative autocrine factor were examined and their impact on the metabolic rates and antibody production of near-physiologically synchronized CHO DP-12 cell cultures was determined. To achieve this, a population resolved model was extended to describe putative autocrine-dependentt and cell-cycle-related metabolic rates for glucose, glutamine, lactate, ammonia, and antibody production. The model parameters were estimated based on data of two repeated batch cultivations (three batches each), with main substrates in excess and potentially inhibiting waste products (lactate and ammonium) controlled within narrow ranges. Significant changes, due to a putative autocrine factor, were identified for lactate and ammonia formation and antibody production. The cell growth and the uptake of glucose and glutamine were only partially affected by the putative autocrine under the given conditions. The results indicate the presence of a self-expressed autocrine factor and its strong impact on the metabolism of CHO DP-12 cells. Furthermore, glucose and glutamine uptake, as well as the formation of ammonium and antibody were found to be significantly cell-cycle-dependent. The combined approach has a strong potential to improve the understanding of the interplay of population heterogeneities and signal factors in mammalian cell culture.

show abstract

Section: Synchronized Cultivationmentioning

confidence: 99%

Model‐based identification of cell‐cycle‐dependent metabolism and putative autocrine effects in antibody producing CHO cell culture

Möller

Korte

Pörtner

et al. 2018

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…In addition, the scale up of different TGE processes in both CHO and HEK cells to industrially relevant volumes have been reported. 15 , 16 These advances have the potential to reduce the time for drug development, as transiently generated material could be used to manufacture therapeutic proteins for toxicology studies or even directly given to patients in a pandemic rapid response scenario. 17 However, historical concerns associated with transient gene expression (e.g., low yields, batch-to-batch consistency) have prevented the use of this technology at later stages of drug development.…”

Section: Discussionmentioning

confidence: 99%

“… 11–15 Tyzack et al . were the first to demonstrate successful scale up of a PEI-mediated TGE process using CHO cells at an industrially relevant scale of 500 L. 16 In an initial run, they were able to scale up their process from 5 L in a rocking bioreactor to 500 L in a single-use bioreactor (SUB), achieving crude titers of 1.50 g/L and 0.83 g/L, respectively. The lower titers observed in the SUB compared to the 5 L rocking bioreactors were attributed to increased cell growth.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Suitability of transiently expressed antibodies for clinical studies: product quality consistency at different production scales

Rodriguez-Conde¹,

Inman

Lindo

et al. 2022

mAbs

View full text Add to dashboard Cite

Transgenic human monoclonal antibodies derived from humanized mice against different epitopes of the Middle East respiratory syndrome coronavirus (MERS-CoV), and chimeric llama-human bispecific heavy chain-only antibodies targeting the Rift Valley fever virus (RVFV), were produced using a CHO-based transient expression system. Two lead candidates were assessed for each model virus before selecting and progressing one lead molecule. MERS-7.7G6 was used as the model antibody to demonstrate batch-to-batch process consistency and, together with RVFV-107-104, were scaled up to 200 L. Consistent expression titers were obtained in different batches at a 5 L scale for MERS-7.7G6. Although lower expression levels were observed for MERS-7.7G6 and RVFV-107-104 during scale up to 200 L, product quality attributes were consistent at different scales and in different batches. In addition to this, peptide mapping data suggested no detectable sequence variants for any of these candidates. Functional assays demonstrated comparable neutralizing activity for MERS-7.7G6 and RVFV-107-104 generated at different production scales. Similarly, MERS-7.7G6 batches generated at different scales were shown to provide comparable protection in mouse models. Our study demonstrates that a CHO-based transient expression process is capable of generating consistent product quality at different production scales and thereby supports the potential of using transient gene expression to accelerate the manufacturing of early clinical material.

show abstract

Abstracts from the 25th European Society for Animal Cell Technology Meeting: Cell Technologies for Innovative Therapies

Cited by 2 publications

References 153 publications

Model‐based identification of cell‐cycle‐dependent metabolism and putative autocrine effects in antibody producing CHO cell culture

Model‐based identification of cell‐cycle‐dependent metabolism and putative autocrine effects in antibody producing CHO cell culture

Suitability of transiently expressed antibodies for clinical studies: product quality consistency at different production scales

Contact Info

Product

Resources

About