Antibody production in packed bed reactors using serum-free and protein-free medium

Bliem, Rudolf; Oakley, Robert B.; Matsuoka, Kinya; Varecka, R; Taiariol, V.

doi:10.1007/bf00563788

Cited by 17 publications

(5 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, these systems are limited in their scalability. Whereas the CellCube allows a linear scaleup to a certain size limited by its practicability (module 400), the concept of the packed bed (basket reactor from NewBrunswick Scientific) is very limited, and the maximum size practically available is a total working volume of about 20 L. A further scale-up would be possible if the system will be modified according to the propositions by Bliem et al (28). The possibility of increasing the run time for increasing the total vector production is limited as a result of clogging of the packed bed reactor in the case of the New Brunswick system, because the TE Fly cells are not contact-inhibited and, in addition, an increase in the run-time might be limited by a potential instability of the producer cell line.…”

Section: Resultsmentioning

confidence: 99%

Comparison of Different Bioreactor Systems for the Production of High Titer Retroviral Vectors

Merten

Cruz

Rochette

et al. 2001

Biotechnology Progress

View full text Add to dashboard Cite

Improved, human-based packaging cell lines allow the production of high-titer, RCR-free retroviral vectors. The utility of these cell lines for the production of clinical grade vectors critically depends on the definition of optimal conditions for scaled-up cultures. In this work, a clone derived from the TE Fly GALV packaging cell (Duisit et al. Hum. Gene Ther. 1999, 10, 189) that produces high titers of a lacZ containing retroviral vector with a Gibbon Ape Leukemia Virus envelope glycoprotein was used. This clone can produce (2-5) x 10(6) PFU cm(-3) in small scale cultures and has been evaluated for growth and vector production in different reactor systems. The performances of fixed bed reactors [CellCube (Costar) and Celligen (New Brunswick)] and stirred tank reactors [microcarriers and clump cultures] were compared. The cells showed a higher apparent growth rate in the fixed bed reactor systems than in the suspension systems, probably as a result of the fact that aggregation and/or formation of clumps led to a reduced viability and reduced growth of cells in the interior of the clumps. As a consequence, the final cell density and number were in average 3- to 7-fold higher in the fixed bed systems in comparison to the suspension culture systems. The average titers obtained ranged from 0.5 to 2.1 x 10(7) PFU cm(-3) for the fixed bed and microcarrier systems, while the clump cultures produced only (2-5) x 10(5) PFU cm(-3). The differences in titers reflect cell densities as well as specific viral vector production rates, with the immobilization and microcarrier systems exhibiting an at least 10-fold higher production rate in comparison to the clump cultures. A partial optimization of the culture conditions in the Celligen fixed bed reactor, consisting of a 9-fold reduction of the seeding cell density, led to a 5-fold increased vector production rate accompanied by an average titer of 3 x 10(7) PFU cm(-3) (maximum titer (4-5) x 10(7) PFU cm(-3)) in the fixed bed reactor. The performance evaluation results using mathematical models indicated that the fixed bed bioreactor has a higher potential for retroviral vector production because of both the higher reactor productivity and the lower sensitivity of productivity in relation to the changes in final retrovirus titer in the range of 3 x 10(6) to 15 x 10(6) PFU cm(-3).

show abstract

Section: Resultsmentioning

confidence: 99%

Comparison of Different Bioreactor Systems for the Production of High Titer Retroviral Vectors

Merten

Cruz

Rochette

et al. 2001

Biotechnology Progress

View full text Add to dashboard Cite

show abstract

“…Packed bed technology was used for production in the past (108). Disadvantages of packed bed technologies are:…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Cell growth on electrospun nanofiber mats from polyacrylonitrile (PAN) blends

Wehlage¹,

Blattner²,

Mamun³

et al. 2020

AIMS Bioengineering

View full text Add to dashboard Cite

show abstract

“…Basket type packed bed reactors were developed very early, largely pioneered by Spier and co-workers [81], and have been scaled by [77] to an approximate bed volume of about 21 L allowing the production of 200-300 L of supernatant per day. The largest established scale of a packed bed reactor is 100 L of bed volume (Bliem, personal communication).…”

Section: Fixed Bed Reactor/packed Bed Reactormentioning

confidence: 99%

“…Such reactors have been used for the production of viral vaccines [81], retroviral vectors [83,122], adenoviral vectors [84], recombinant proteins, and monoclonal antibodies [65,77,85,87].…”

Section: Fixed Bed Reactor/packed Bed Reactormentioning

confidence: 99%

See 1 more Smart Citation

State-of-the-art of the production of retroviral vectors

Merten

2004

J. Gene Med.

View full text Add to dashboard Cite

Retroviral vectors are still the vectors that are used in the majority of gene therapy trials for treatment of acquired or inherited diseases. In this review, the present state-of-the-art of the production of retroviral vectors and the most important parameters, such as the choice of the producer cell line, stability issues, medium additives, serum, type of bioreactor, that influence production issues is presented and discussed in light of an optimal vector production. The available literature data clearly indicate that, on one hand, the choice of the producer cell line is of utmost importance for obtaining a high level producer cell line, and that, on the other hand, the optimization of the medium, e.g. the replacement of glucose by fructose, has a potential for improving vector production rates and titers. Finally, the use of high-density perfusion culture systems for adherent as well as for suspension cells presents the best choice for a production system, because high cell densities imply high reactor specific production rates, which must be associated with a rapid harvest of the produced vector, thus avoiding vector inactivation due to an extended residence time. The overall optimization of the cultivation and production parameters will have a significant impact on the use of retroviral vectors for gene therapy purposes.

show abstract

Antibody production in packed bed reactors using serum-free and protein-free medium

Cited by 17 publications

References 3 publications

Comparison of Different Bioreactor Systems for the Production of High Titer Retroviral Vectors

Comparison of Different Bioreactor Systems for the Production of High Titer Retroviral Vectors

Cell growth on electrospun nanofiber mats from polyacrylonitrile (PAN) blends

State-of-the-art of the production of retroviral vectors

Contact Info

Product

Resources

About