Genetic analyses of Per.C6 cell clones producing a therapeutic monoclonal antibody regarding productivity and long-term stability

Tsuruta, Lilian Rumi; Santos, Mariana Lopes dos; Yeda, Fernanda Perez; Okamoto, Oswaldo Keith; Moro, Ana Maria

doi:10.1007/s00253-016-7841-9

Cited by 8 publications

(8 citation statements)

References 51 publications

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“…Considering the extensive mutagenesis and clonal selection of the derived CHO host cell lines, we assume that the determined expression differences related to the cellular phenotype and metabolism rather than differences in product‐specific GCN (or mRNA), location of the transgenes, or type of cell cultivation. The influence of GCN and amount of transcript on protein expression levels is addressed since a long time by several publications and remains controversial …”

Section: Discussionmentioning

confidence: 99%

Bioprocessing of Recombinant CHO-K1, CHO-DG44, and CHO-S: CHO Expression Hosts Favor Either mAb Production or Biomass Synthesis

et al. 2018

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Chinese hamster ovary (CHO) cells comprise a variety of lineages including CHO-DXB11, CHO-K1, CHO-DG44, and CHO-S. Despite all CHO cell lines sharing a common ancestor, extensive mutagenesis, and clonal selection has resulted in substantial genetic heterogeneity among them. Data from sequencing show that different genes are missing in individual CHO cell lines and each cell line harbors a unique set of mutations with relevance to the bioprocess. However, not much literature is available about the influence of genetic differences of CHO on the performance of bioprocess operations. In this study, the host cell-specific differences among three widely used CHO cell lines (CHO-K1, CHO-S, and CHO-DG44) and recombinantly expressed the same monoclonal antibody (mAb) in an isogenic format by using bacterial artificial chromosomes (BACs) as transfer vector in all cell lines is examined. Cell-specific growth and product formation are studied in batch, fed-batch, and semi-continuous perfusion cultures. Further, two different cell culture media are used to investigate their effects. The authors find CHO cell line-specific preferences for mAb production or biomass synthesis that are determined by the host cell line. Additionally, quality attributes of the expressed mAb are influenced by the host cell line and media.

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Section: Discussionmentioning

confidence: 99%

Bioprocessing of Recombinant CHO-K1, CHO-DG44, and CHO-S: CHO Expression Hosts Favor Either mAb Production or Biomass Synthesis

et al. 2018

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“…The PER.C6 cells are human embryonic retinal cells, and like HEK cells are pointed out to promote human glycosylation profiles. They were projected to be grown in high-density conditions [71], with stable expression and also offer production yields similar to CHO cells, indicating that human cell lines will be more economically viable and more easily scalable options for antibody productions [72]. There is even description of a production with titers of 27 g/L of antibody, astounding yields when compared to a medium CHO cell production of around 12 g/L of antibodies [73].…”

Section: Alternative Methods For Mab Production 31 Mammalian Productmentioning

confidence: 99%

Alternative Methods to Animal Use for Monoclonal Antibody Generation and Production

Moraes¹,

Hamaguchi²,

Braggion³

et al. 2021

Monoclonal Antibodies

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Monoclonal antibody (mAb) has broad applicability in research, diagnosis, and treatment. After the introduction of hybridoma technology in 1975, the mAb market has increased dramatically, moving a large industry of more than US$ 140 billions in 2020. In 1954, the concept of the 3R’s was proposed and much changed the animal use scenario, including the recent ban on inducing ascites in mice for the production of mAb. In light of this, the generation and production of antibodies had to be reassessed. In this chapter, we present an overview of the main alternative technologies to the use of animals in the generation and production of mAb. Antibody display libraries and in silico modeling are very promising technologies that may provide mAb genetic constructs that, in the sequence, may be expressed on mammalian, bacterial, yeast or plant systems. Although the total replacement of the use of animals in the entire process is not currently feasible, it is possible to find ways to reduce and refine the use of animals in obtaining and producing mAb.

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“…Human cell lines able to accomplish complete human post translation modified proteins as HEK cells had Fc-fusion drugs approved more recently. The PER.C6 cells, of human origin as well, have been used in the development of innovator mAbs (Lopes dos Santos et al, 2013;Tsuruta et al, 2016). Parallel developments claim that plants might represent increased production capacity and, trying to surpass immunogenic potential, plant cells have been engineered to express human transferases (Komarova et al, 2017).…”

Section: Perspectivesmentioning

confidence: 99%

Advances and challenges in therapeutic monoclonal antibodies drug development

Santos

Quintilio

Manieri

et al. 2018

Braz. J. Pharm. Sci.

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The use of serum containing polyclonal antibodies from animals immunized with toxins marked the beginning of the application of antibody-based therapy in late nineteenth century. Advances in basic research led to the development of the hybridoma technology in 1975. Eleven years later, the first therapeutic monoclonal antibody (mAb) was approved, and since then, driven by technological advances, the development of mAbs has played a prominent role in the pharmaceutical industry. In this review, we present the developments to circumvent problems of safety and efficacy arising from the murine origin of the first mAbs and generate structures more similar to human antibodies. As of October 2017, there are 61 mAbs and 11 Fc-fusion proteins in clinical use. An overview of all mAbs currently approved is provided, showing the development of sophisticated mAbs formats that were engineered based on the challenges posed by therapeutic indications, including antibody-drug conjugates (ADC) and glycoengineered mAbs. In the field of immunotherapy, the use of immunomodulators, bispecific mAbs and CAR-T cells are highlighted. As an example of promising therapy to treat infectious diseases, we discuss the generation of neutralizing monoclonal-oligoclonal antibodies obtained from human B cells. Scientific and technological advances represent mAbs successful translation to the clinic.

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Genetic analyses of Per.C6 cell clones producing a therapeutic monoclonal antibody regarding productivity and long-term stability

Cited by 8 publications

References 51 publications

Bioprocessing of Recombinant CHO-K1, CHO-DG44, and CHO-S: CHO Expression Hosts Favor Either mAb Production or Biomass Synthesis

Bioprocessing of Recombinant CHO-K1, CHO-DG44, and CHO-S: CHO Expression Hosts Favor Either mAb Production or Biomass Synthesis

Alternative Methods to Animal Use for Monoclonal Antibody Generation and Production

Advances and challenges in therapeutic monoclonal antibodies drug development

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