Differential response of type C and intracisternal type A particle markers in cells treated with iododeoxyuridine and dexamethasone

Kuff, Edward L.; Lueders, Kira K.; Orenstein, J M; Wilson, Samuel H.

doi:10.1128/jvi.19.2.709-716.1976

Cited by 10 publications

(3 citation statements)

References 22 publications

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“…Since adult BL/Ks db/db mice have been shown to contain increased levels of plasma corticosterone [10], and since glucocorticoid administration can enhance C-and B-particle expression [12,13], the ability of hydrocortisone and dexamethasone to enhance IAP production in high glucose DMEM was examined. The apparent insensitivity of type A particle synthesis to glucocorticoids found in this system is consistent with the similar negative findings of Kuff, Lueders, Orenstein, and Wilson [20] using cultured mouse neuroblastoma cells. It would appear, therefore, that pancreatic intracisternal type A production is under separate regulatory controls than are the other types of retroviruses, and thus are unlikely to be precursors of C-particles.…”

Section: Discussionsupporting

confidence: 91%

Intracisternal A-particles in genetically diabetic mice: Identification in pancreas and induction in cultured beta cells

Leiter

Bedigian

1979

Diabetologia

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Sucrose density gradient analysis of purified pancreatic homogenates from glycaemic C57BL/Ks diabetes (db/db) mice and their normoglycaemic controls have revealed the presence in the diabetics of increased Mg++-dependent RNA-directed DNA polymerase activity sedimenting with a density of approximately 1.21 g/cm3. Electron microscopy revealed that this fraction contained typical intracisternal A-particles. Purified cultures of pancreatic islet cells 4--7 day old postnatal "misty diabetic" mice and normal siblings were established and then maintained in Eagle's minimal essential medium without serum. Under these conditions, the presence of intracisternal A-particles in beta cells of both mutant and control genotypes was very rare. No change in numbers of intracisternal A-particles was seen after 2--4 days of incubation in Dulbecco's-modified minimal essential medium containing 5.5 mmol/l glucose. However, when the glucose concentration of Dulbecco's medium was elevated to 16.5 mmol/l, ultrastructural changes specific to the beta cell population occurred that were reminiscent of those alterations observed in situ. Intracisternal A-particles were commonly seen in cultured beta cells showing hypersecretion-stress morphology. Since equal numbers of intracisternal A-particles were present in cultured beta cells from normal and mutant mice, it was concluded that the db gene itself was not required for intracisternal A-particle expression. The cell culture results suggest that elevated intracisternal A-particle activity observed in vivo may be produced directly or indirectly by the ambient high blood glucose levels characteristic of this mutant.

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Section: Discussionsupporting

confidence: 91%

Intracisternal A-particles in genetically diabetic mice: Identification in pancreas and induction in cultured beta cells

Leiter

Bedigian

1979

Diabetologia

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“…Mammalian tissue culture-derived biopharmaceuticals are at risk of virus/viral particle contamination (Anderson et al, 1990(Anderson et al, , 1991aBartal et al, 1982;Deo et al, 1994;Dinowitz et al, 1992;Garnick 1996;Jenkins and Copeland 1987;Kuff et al, 1976;Lieber et al, 1973;Lueders, 1991), some having tumorigenic capabilities (Donahue et al, 1992;Pedersen et al, 1982;Quint et al, 1981;van der Putten et al, 1981). As such, regulatory agencies expect risk mitigation strategies including validation of purification unit operations for their ability to clear viruses (ICH, 1999).…”

Section: Introductionmentioning

confidence: 99%

Analysis of viral clearance unit operations for monoclonal antibodies

Miesegaes

Lute

Brorson

2010

Biotech & Bioengineering

117

140

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Demonstration of viral clearance is a critical step in assuring the safety of biotechnology products. We generated a viral clearance database that contains product information, unit operation process parameters, and viral clearance data from monoclonal antibody and antibody-related regulatory submissions to FDA. Here we present a broad overview of the database and resulting analyses. We report that the diversity of model viruses tested expands as products transition to late-phase. We also present averages and ranges of viral clearance results by Protein A and ion exchange chromatography steps, low pH chemical inactivation, and virus filtration, focusing on retro- and parvoviruses. For most unit operations, an average log reduction value (LRV, a measure of clearance power) for retrovirus of >4 log(10) were measured. Cases where clearance data fell outside of the anticipated range (i.e., outliers) were rationally explained. Lastly, a historical analysis did not find evidence of any improvement trend in viral clearance over time. The data collectively suggest that many unit operations in general can reliably clear viruses.

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“…Viral safety is a critical concern for biologicals intended for in vivo human use (e.g., monoclonal antibodies [mAbs], recombinant proteins [RPs]) when they are produced using mammalian cell cultures (e.g., murine hybridomas, transfected Chinese hamster ovary [CHO] cells). One concern arises because rodent cell cultures produce endogenous type C retrovirus or retrovirus-like particles (up to 10 9 /mL; Anderson et al, 1991b;Bartal et al, 1982;Lieber et al, 1973), as their genomes contain multiple copies of retrovirus-like sequences (Anderson et al, 1990(Anderson et al, , 1991bJenkins and Copeland, 1987;Kuff et al, 1976;Lueders, 1991). The retrovirus sequences in murine cells encode for at least four types of infectious viruses (Deo et al, 1994;Lueders, 1991), while type C particles produced by CHO cells are undetectable in infectivity assays (Anderson et al, 1991a;Dinowitz et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Impact of cell culture process changes on endogenous retrovirus expression

Brorson¹,

Wit²,

Hamilton³

et al. 2002

Biotech & Bioengineering

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Cell culture process changes (e.g., changes in scale, medium formulation, operational conditions) and cell line changes are common during the development life cycle of a therapeutic protein. To ensure that the impact of such process changes on product quality and safety is minimal, it is standard practice to compare critical product quality and safety attributes before and after the changes. One potential concern introduced by cell culture process improvements is the possibility of increased endogenous retrovirus expression to a level above the clearance capability of the subsequent purification process. To address this, retrovirus expression was measured in scaled down and full production scaled Chinese hamster ovary (CHO) cell cultures of four monoclonal antibodies and one recombinant protein before and after process changes. Two highly sensitive, quantitative (Q)-PCR-based assays were used to measure endogenous retroviruses. It is shown that cell culture process changes that primarily alter media components, nutrient feed volume, seed density, cell bank source (i.e., master cell bank vs. working cell bank), and vial size, or culture scale, singly or in combination, do not impact the rate of retrovirus expression to an extent greater than the variability of the Q-PCR assays (0.2-0.5 log(10)). Cell culture changes that significantly alter the metabolic state of the cells and/or rates of protein expression (e.g., pH and temperature shifts, NaButyrate addition) measurably impact the rate of retrovirus synthesis (up to 2 log(10)). The greatest degree of variation in endogenous retrovirus expression was observed between individual cell lines (up to 3 log(10)). These data support the practice of measuring endogenous retrovirus output for each new cell line introduced into manufacturing or after process changes that significantly increase product-specific productivity or alter the metabolic state, but suggest that reassessment of retrovirus expression after other process changes may be unnecessary.

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Differential response of type C and intracisternal type A particle markers in cells treated with iododeoxyuridine and dexamethasone

Cited by 10 publications

References 22 publications

Intracisternal A-particles in genetically diabetic mice: Identification in pancreas and induction in cultured beta cells

Intracisternal A-particles in genetically diabetic mice: Identification in pancreas and induction in cultured beta cells

Analysis of viral clearance unit operations for monoclonal antibodies

Impact of cell culture process changes on endogenous retrovirus expression

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