Viral vector manufacturing: how to address current and future demands?

Masri, Fernanda; Cheeseman, E. A.; Ansorge, Sven

doi:10.18609/cgti.2019.104

Cited by 21 publications

(25 citation statements)

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Section: Discussionmentioning

confidence: 99%

“…Until a robust LV manufacturing process is established, the transition to continuous production and purification will be difficult to apply to a larger scale but research at a lab-scale is already committed to these new processing operation modes. [113][114][115] In this review, some future directions were identified, and the progress made in the manufacturing of LV was described. Some success stories have already been reported and novel applications and technological developments are thriving.…”

Section: Discussionmentioning

confidence: 99%

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Advances in Lentivirus Purification

Moreira

Cavaco

Faria

et al. 2020

Biotechnology Journal

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Lentiviral vectors (LVs) have been increasingly used as a tool for gene and cell therapies since they can stably integrate the genome in dividing and nondividing cells. LV production and purification processes have evolved substantially over the last decades. However, the increasing demands for higher quantities with more restrictive purity requirements are stimulating the development of novel materials and strategies to supply the market with LV in a cost-effective manner. A detailed review of each downstream process unit operation is performed, limitations, strengths, and potential outcomes being covered. Currently, the majority of large-scale LV manufacturing processes are still based on adherent cell culture, although it is known that the industry is migrating fast to suspension cultures. Regarding the purification strategy, it consists of batch chromatography and membrane technology. Nevertheless, new solutions are being created to improve the current production schemes and expand its clinical use.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Advances in Lentivirus Purification

Moreira

Cavaco

Faria

et al. 2020

Biotechnology Journal

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“…4 Therefore, if productivity improvement in large scale is not related to the composition of the bioreactor bed, but rather to other large-scale process parameters such as antibiotic-free production, and the same occurs also in large-scale scale-X bioreactor, it is possible that >1 • 10 13 TU (titered in our HeLa cells) or >1 • 10 16 vp are achieved in scale-X nitro bioreactor. 1 As both iCELLis and scale-X bioreactors are intended for adherent use, it is true that they have limited scalability. With suspension bioreactor scalability is less limited, and, for example, the use of 2,000 L suspension bioreactor would massively increase productivity.…”

Section: Lentiviral Vector Yields In Icellis Nano and Scale-x Bioreacmentioning

confidence: 99%

“…However, they require a lot of manual handling, may need open connections, and are not monitored or controlled for pH, dissolved oxygen, and so on. 1 Thus, there has been a need for large-scale, disposable bioreactor for adherent cells. ATMI/Pall brought iCELLis Ò fixed-bed technology on market about a decade ago.…”

Section: Introductionmentioning

confidence: 99%

Benchmarking of Scale-X Bioreactor System in Lentiviral and Adenoviral Vector Production

et al. 2020

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We have previously produced viral vectors (lentiviral vector, adenoviral vector, and adeno-associated viral vector) in small and in commercial scale in adherent cells using Pall fixed-bed iCELLis Ò bioreactor. Recently, a company called Univercells has launched a new fixed-bed bioreactor with the same cell growth surface matrix material, but with different fixed-bed structure than is used in iCELLis bioreactor. We sought to compare the new scale-XÔ hydro bioreactor (2.4 m 2) and iCELLis Nano system (2.67 m 2) to see if the difference has any effect on cell growth or lentiviral vector and adenoviral vector productivity. Runs were performed using parameters optimized for viral vector production in iCELLis Nano bioreactor. Cell growth was monitored by counting nuclei, as well as by following glucose consumption and lactate production. In both bioreactor systems, cells grew well, and the cell distribution was found quite homogeneous in scale-X bioreactor. Univercells scale-X bioreactor was proven to be at least equally efficient or even improved in both lentiviral vector and adenoviral vector production. Based on the results, the same protocol and parameters used in viral vector production in iCELLis bioreactor can also be successfully used for the production in scale-X bioreactor system.

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“…Ideally, MOI should be kept low to ensure single transgene integrations to limit the risk of cytotoxicity and tumorigenic potential [ 22 , 23 , 24 ]. Ultimately, there is no apparent fixed titre of vector required, but annual transducing units (TU) from manufacturing processes can range from

TU depending on patient numbers and dosing [ 25 ]. The sensitivity of autologous cell therapies to scalable viral production is indicated in some cost of goods analysis, with up to 26% contribution to cost when viral titre is poor [ 26 ].…”

Section: Bioprocessing Of Lentiviral Vectorsmentioning

confidence: 99%

Lentiviral Vector Bioprocessing

Perry

Rayat

2021

Viruses

101

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Lentiviral vectors (LVs) are potent tools for the delivery of genes of interest into mammalian cells and are now commonly utilised within the growing field of cell and gene therapy for the treatment of monogenic diseases and adoptive therapies such as chimeric antigen T-cell (CAR-T) therapy. This is a comprehensive review of the individual bioprocess operations employed in LV production. We highlight the role of envelope proteins in vector design as well as their impact on the bioprocessing of lentiviral vectors. An overview of the current state of these operations provides opportunities for bioprocess discovery and improvement with emphasis on the considerations for optimal and scalable processing of LV during development and clinical production. Upstream culture for LV generation is described with comparisons on the different transfection methods and various bioreactors for suspension and adherent producer cell cultivation. The purification of LV is examined, evaluating different sequences of downstream process operations for both small- and large-scale production requirements. For scalable operations, a key focus is the development in chromatographic purification in addition to an in-depth examination of the application of tangential flow filtration. A summary of vector quantification and characterisation assays is also presented. Finally, the assessment of the whole bioprocess for LV production is discussed to benefit from the broader understanding of potential interactions of the different process options. This review is aimed to assist in the achievement of high quality, high concentration lentiviral vectors from robust and scalable processes.

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Viral vector manufacturing: how to address current and future demands?

Cited by 21 publications

References 0 publications

Advances in Lentivirus Purification

Advances in Lentivirus Purification

Benchmarking of Scale-X Bioreactor System in Lentiviral and Adenoviral Vector Production

Lentiviral Vector Bioprocessing

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