Nutrient optimization for high density biological production applications

Jayme, David W.

doi:10.1007/bf00365531

Cited by 43 publications

(18 citation statements)

References 38 publications

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“…Enhancements in both specific MAb productivity and yields have been previously reported with the use of this agent (Fike, 1990;Fike et al, 1991a;1991b;Jayme, 1991). In a previous study, we have shown that addition of OptiMAb TM to batch cultures of D5 hybridoma cells resulted in an increase in the G 1 phase population, in a 50% increase in specific MAb production rate and in an overall enhancement of MAb concentration .…”

Section: Introductionsupporting

confidence: 63%

Apoptosis-resistant NS/0 E1B-19K myelomas exhibit increased viability and chimeric antibody productivity under cell cycle modulating conditions

Mercille

Massie

1998

Current Applications of Cell Culture Engineering

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Lymphoid cells expressing sufficient levels of Bcl-2 or E1B-19K are known to resist to induction of apoptosis in glutamine-free or nutrient-limited batch cultures. However, despite the increased viability and prolonged stationary phase achieved in batch culture, product yields are not necessarily improved. Here we have found that expression of E1B-19K in NS/0 myeloma cells cultivated in the presence of certain cell cycle modulators could result in a significant increase in MAb productivity as compared to untransfected control cells. The use of E1B-19K significantly enhanced cell survival in the presence of osmolytes (sorbitol, NaCl), DNA synthesis inhibitors (hydroxyurea, excess thymidine), and the cell culture additive OptiMAb TM . E1B-19K myelomas cultivated in the presence of NaCl or OptiMAb TM accumulated in the G 1 phase, while those arrested with excess thymidine were blocked in all phases. Interestingly, control NS/0 cells treated with these agents were found to die in a cell-cycle specific manner. Thus, while all G 1 and most S phase cells quickly underwent apoptosis, G 2 /M cells remained alive and maintained MAb secretion for more than 10 days if supplied with adequate nutrients. For both control and E1B-19K cells, incubation with sorbitol or hydroxyurea was detrimental for MAb secretion, while addition of NaCl, excess thymidine and OptiMAb TM resulted in an increased specific MAb productivity as compared to the batch culture. However, this increase resulted in an improvement of final MAb yields only in the case of OptiMAb TM . The extension of viability conferred by E1B-19K allowed to further improve the final MAb yield obtained using OptiMAb TM with a 3.3-fold increase for E1B-19K cells as compared to 1.8-fold for control NS/0 cells.

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Section: Introductionsupporting

confidence: 63%

Apoptosis-resistant NS/0 E1B-19K myelomas exhibit increased viability and chimeric antibody productivity under cell cycle modulating conditions

Mercille

Massie

1998

Current Applications of Cell Culture Engineering

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“…This has been observed for cells cultivated in batch (Ramirez and Mutharasan, 1990), fed-batch (de Tremblay et al, 1993;Robinson et al, 1994), chemostat (Boraston et al, 1984), and perfusion modes (Al-Rubeai et al, 1992;Banik and Heath, 1995;Batt et al, 1990;de la Broise et al, 1991;Johnson et al, 1996;Hansen et al, 1993;Park and Ryu, 1994;Tokashiki and Takamatsu, 1993;Trampler et al, 1994), as well as in cells treated with cell-cycle blocking agents (Al-Rubeai and Emery, 1990;Jayme, 1991;Mercille and Massie, 1998;Oh et al, 1995;Øyaas et al, 1994a,b;Reddy and Miller, 1994;Suzuki and Ollis, 1990;Takahachi et al, 1994). Indeed, specific antibody production has been shown to be cell cycle dependent and optimum in the G 1 and/or G 2 /M phase (Cazzador and Mariani, 1993;Kromenaker and Srienc, 1991;Linardos et al, 1992;Richieri et al, 1991;Suzuki and Ollis, 1989).…”

Section: Introductionmentioning

confidence: 83%

Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions

Mercille¹,

Massie²

1999

Biotechnol. Bioeng.

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“…Usually HS is considerably less e#ective than FBS in supporting proliferation of piscine (Ganassin & Bols, 1992) and mammalian cell lines (Jayne, 1991). For the trout spleen, macrophages might be less sensitive to detrimental factors or more responsive to maintenance factors in HS than other cell types in the spleen cell suspension.…”

Section: Non-haemopoietic Cell Culturesmentioning

confidence: 99%

Development of long-term rainbow trout spleen cultures that are haemopoietic and produce dendritic cells

Ganassin

Bols

1996

Fish & Shellfish Immunology

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Nutrient optimization for high density biological production applications

Cited by 43 publications

References 38 publications

Apoptosis-resistant NS/0 E1B-19K myelomas exhibit increased viability and chimeric antibody productivity under cell cycle modulating conditions

Apoptosis-resistant NS/0 E1B-19K myelomas exhibit increased viability and chimeric antibody productivity under cell cycle modulating conditions

Apoptosis-resistant E1B-19K-expressing NS/0 myeloma cells exhibit increased viability and chimeric antibody productivity under perfusion culture conditions

Development of long-term rainbow trout spleen cultures that are haemopoietic and produce dendritic cells

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