Production of immunoglobulin A in different reactor configurations

Stoll, T. S.; Perregaux, Christine; Stockar, Urs von; Marison, I. W.

doi:10.1007/bf00749221

Cited by 17 publications

(3 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, this reaction is highly dependent on the culture environment, such as temperature and pH [7]. Pyrrolidonecarboxylic acid at a high concentration (20 mM) is not toxic to the cells [21], but ammonia concentration at a low concentration (4.3 mM) can have negative effects on cell growth and glycoprotein production.…”

Section: Ammonia Accumulation In Culture Mediummentioning

confidence: 99%

Glutamine substitution: the role it can play to enhance therapeutic protein production

Ha¹,

Lee²

2015

Pharmaceutical Bioprocessing

View full text Add to dashboard Cite

The biopharmaceutical market is driven by the steady increase in demand for therapeutic proteins produced in mammalian cells. Glutamine is a main nitrogen source and also a main energy source with glucose in mammalian cell cultures for therapeutic protein production. As a result of glutamine metabolism and the natural decomposition of glutamine, ammonia, which is known to negatively affect cell growth, protein production and sialylation of recombinant glycoprotein, is necessarily accumulated in a culture medium. This review highlights the current strategies and achievements in overcoming the negative effect of ammonia through the glutamine substitution by less ammoniagenic substrates, such as glutamate, pyruvate and α-ketoglutarate.

show abstract

Section: Ammonia Accumulation In Culture Mediummentioning

confidence: 99%

Glutamine substitution: the role it can play to enhance therapeutic protein production

Ha¹,

Lee²

2015

Pharmaceutical Bioprocessing

View full text Add to dashboard Cite

show abstract

“…The HFB was first developed in the early 1970s in an attempt to grow cells in a more tissue‐like environment [20]. Since then, a major use of the HFB has been production of monoclonal antibodies, since antibody concentrations in the supernatant of the ECS can approach ascites concentration [21–23]. When concerns about cruelty to mice for ascites production arose, the HFB proved to be a viable alternative [22,24,25].…”

Section: Introductionmentioning

confidence: 99%

Recombinant‐protein production in insect cells utilizing a hollow‐fibre bioreactor

Baxter

Panarello

Ajith

et al. 2006

Biotech and App Biochem

View full text Add to dashboard Cite

Here, we demonstrate for the first time that the hollow-fibre bioreactor is an excellent tool for the production of Drosophila-expressed recombinant proteins. Using the example of the soluble extracellular portion of the human IL-5 (interleukin 5) receptor alpha expression in S2 (Schneider's Drosophila melanogaster cell line 2) cells, we found that it is possible to produce multi-milligram amounts of functional recombinant protein continuously for several months on a laboratory scale with minimal maintenance requirements. The insect cells grow to high density and express concentrated functional recombinant protein in a small volume, simplifying and economizing downstream purification.

show abstract

“…The concentration of viable cells attained in suspension cultures is usually low, 10 6 cells/ml (Katinger 1987;Altshuler et al 1987;Ramirez and Mutharasan 1990;Hayter et al 1992;Jan et al 1997;Cherlet and Marc 2002). Consequently, MAb concentration (usually less than 100 mg/l) and volumetric productivity (usually 20-70 mg/lÁday) are also low as compared to those from in vivo cultivation in mouse or rabbit ascites (Stoll et al 1995;Jackson et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Long-term Continuous Production of Monoclonal Antibody by Hybridoma Cells Immobilized in a Fibrous-Bed Bioreactor

Zhu¹,

Yang

2004

Cytotechnology

View full text Add to dashboard Cite

The kinetics and long-term stability of continuous production of monoclonal antibody IgG2b by hybridoma HD-24 cells immobilized in a fibrous-bed bioreactor (FBB) were studied for a period of approximately 8 months. The cells were immobilized in the fibrous bed by surface attachment of cells and entrapment of large cell clumps in the void space of the fibrous matrix. A high viable cell density of 1.01 x 10(8)/ml was attained in the bioreactor, which was about 63 times higher than those in conventional T-flask and spinner flask cultures. The continuous FBB produced IgG at a concentration of approximately 0.5 g/l, with reactor productivity of approximately 7 mg/h.l, which was about 23 times higher than those from conventional T-flask and spinner flask cultures. The IgG concentration can be further increased to approximately 0.67 g/l by using higher feed (glucose and glutamine) concentrations and running the reactor at a recycle batch or fed-batch mode. The long-term performance of this bioreactor was also evaluated. For a period of 36 days monitored, the MAb produced in the continuous well-mixed bioreactor at 50 h retention time (0.02/h dilution rate) was maintained at a steady concentration level of approximately 0.3 g/l with less than 8% drift. At the end of the study, it was found that approximately 25% of the cells were strongly attached to the fiber surfaces and the other approximately 75% entrapped or weakly immobilized in the fibrous matrix. The strongly attached cells had a high viability of approximately 90%, compared to approximately 75% for cells weakly immobilized and only approximately 1.4% for freely suspended cells, suggesting that the fibrous matrix preferentially retained and protected the viable (productive) cells. The FBB thus was able to maintain its long-term productivity because nonviable and dead cells were continuously washed off from the fibrous matrix. The high MAb concentration and production rate and excellent stability for continuous long-term production obtained in this study compare favorably to other bioreactor studies reported in the literature. The reactor performance can be further improved by providing better pH and aeration controls at higher feed concentrations. The FBB is easy to operate and scale-up, and thus can be used economically for industrial production of MAb.

show abstract

Production of immunoglobulin A in different reactor configurations

Cited by 17 publications

References 17 publications

Glutamine substitution: the role it can play to enhance therapeutic protein production

Glutamine substitution: the role it can play to enhance therapeutic protein production

Recombinant‐protein production in insect cells utilizing a hollow‐fibre bioreactor

Long-term Continuous Production of Monoclonal Antibody by Hybridoma Cells Immobilized in a Fibrous-Bed Bioreactor

Contact Info

Product

Resources

About