The glycosylation of anti-rhIFN-α2b recombinant antibodies influences the antigen-neutralizing activity

Attallah, Carolina; Aguilar, María Fernanda; Forno, Guillermina; Etcheverrigaray, Marina; Brigido, Marcelo M.; Maranhão, Andréa Queiroz; Oggero, Marcos

doi:10.1007/s10529-020-02879-0

Cited by 5 publications

(7 citation statements)

References 37 publications

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“…Furthermore, CHO cells lack N-acetylglucosamine transferase (GnT-III) expressed by human cells, resulting in the differences in the modification of N-acetylglucosamine glycosylation from human cells ( Butler, 2005 ). These findings indicate that different cell types produce different types of antibody glycosylation ( Attallah et al, 2020 ; Dyukova et al, 2021 ; Zhao et al, 2021 ). In summary, the type of glycosylation modification of monoclonal antibody drugs is closely related to the production system, selected cell line, and incubation process.…”

Section: Control Glycosylation Modificationmentioning

confidence: 84%

Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells

Zhang

Shan

Liang

et al. 2022

Front. Bioeng. Biotechnol.

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Recombinant antibodies are rapidly developing therapeutic agents; approximately 40 novel antibody molecules enter clinical trials each year, most of which are produced from Chinese hamster ovary (CHO) cells. However, one of the major bottlenecks restricting the development of antibody drugs is how to perform high-level expression and production of recombinant antibodies. The high-efficiency expression and quality of recombinant antibodies in CHO cells is determined by multiple factors. This review provides a comprehensive overview of several state-of-the-art approaches, such as optimization of gene sequence of antibody, construction and optimization of high-efficiency expression vector, using antibody expression system, transformation of host cell lines, and glycosylation modification. Finally, the authors discuss the potential of large-scale production of recombinant antibodies and development of culture processes for biopharmaceutical manufacturing in the future.

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Section: Control Glycosylation Modificationmentioning

confidence: 84%

Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells

Zhang

Shan

Liang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Moreover, there are clear relationships between the structure and function of antibody glycans [ 57 ], so it is important to control the factors that are critical for antibody glycosylation in a bioprocess to ensure the desired function. In particular, it has recently been shown that differences in the glycosylation of the Fc region of anti-hIFN-α2b tend to modify the in vitro neutralization capacity of this particular molecule [ 58 ]. Therefore, the glucose and lactate levels of the CHO-ahIFNα2b culture media over time were quantified in the LM bioreactor and T-flask in parallel.…”

Section: Resultsmentioning

confidence: 99%

“…The mAbs exhibited a significantly higher binding capacity when they and the cytokines were in the liquid phase under experimental conditions. One possible explanation for what is observed here is that epitope binding of the mAb may be affected by antibody glycosylation, which, in turn, may vary by glucose availability [ 58 ].…”

Section: Resultsmentioning

confidence: 99%

“…The mechanism of this effect could involve the transformation of the binding site structure into a kinetically more competent mAbs with higher binding affinities [ 61 ]. Considering that anti-hIFN-α2b has N-glycosylation sites in its Fc region, glycosylation can be affected by the culture conditions in terms of glucose availability and this, in turn, can affect mAb binding as was demonstrated by Attallah et al, 2020 [ 58 ]. Future studies focused on the characterization of the anti-hIFN-α2b glycosylation are planned.…”

Section: Resultsmentioning

confidence: 99%

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Large Area Microfluidic Bioreactor for Production of Recombinant Protein

et al. 2022

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To produce innovative biopharmaceuticals, highly flexible, adaptable, robust, and affordable bioprocess platforms for bioreactors are essential. In this article, we describe the development of a large-area microfluidic bioreactor (LM bioreactor) for mammalian cell culture that works at laminar flow and perfusion conditions. The 184 cm2 32 cisterns LM bioreactor is the largest polydimethylsiloxane (PDMS) microfluidic device fabricated by photopolymer flexographic master mold methodology, reaching a final volume of 2.8 mL. The LM bioreactor was connected to a syringe pump system for culture media perfusion, and the cells’ culture was monitored by photomicrograph imaging. CHO-ahIFN-α2b adherent cell line expressing the anti-hIFN-a2b recombinant scFv-Fc monoclonal antibody (mAb) for the treatment of systemic lupus erythematosus were cultured on the LM bioreactor. Cell culture and mAb production in the LM bioreactor could be sustained for 18 days. Moreover, the anti-hIFN-a2b produced in the LM bioreactor showed higher affinity and neutralizing antiproliferative activity compared to those mAbs produced in the control condition. We demonstrate for the first-time, a large area microfluidic bioreactor for mammalian cell culture that enables a controlled microenvironment suitable for the development of high-quality biologics with potential for therapeutic use.

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“…However, this efficacy is largely limited by its low halflife and bioavailability, a problem that researchers hope to solve by changing its glycosylation pattern among other modifications [14]. In the autoimmunity realm, Fc glycosylation of anti-human IFN-alpha2b antibodies has been shown to influence their binding affinity, thus potentially affecting their efficacy in treating Systemic Lupus Erythematous [15]. In haematology, certain glycosylation patterns on Factor XIII-B prolonged its serum half-life, affecting the body ' s coagulative balance [16].…”

Section: Glycosylating Pharmaceuticals For Delivery Improvementmentioning

confidence: 99%

Sweetening the Deal: Glycosylation and its Clinical Applications

Zhang¹,

Sun²

2020

IPJBS

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Glycosylation, an important and nearly ubiquitous form of post-translational modification in eukaryotes, has been studied for its clinical applications. Its complex nature and heterogeneity of functions in the human body has allowed researchers to take multiple approaches in applying it to modern medicine. These approaches include glycosylation of pharmaceuticals to improve delivery; using glycosylation as vaccine/drug targets; editing the glycosylation pattern of immune system components; and profiling glycosylation signatures of diseases for diagnostic tests. In addition, glycosylation has also been used as a tool in developing potential therapeutics for the Covid-19 pandemic. This review covers and summarizes recent, interesting findings associated with the various approaches in the clinical study of glycosylation and aims to inspire future research in this promising direction.

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The glycosylation of anti-rhIFN-α2b recombinant antibodies influences the antigen-neutralizing activity

Cited by 5 publications

References 37 publications

Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells

Strategies and Considerations for Improving Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells

Large Area Microfluidic Bioreactor for Production of Recombinant Protein

Sweetening the Deal: Glycosylation and its Clinical Applications

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