铵离子和葡萄糖对悬浮及固定床杂交瘤培养中单克隆抗体产生的影响。

Influence of ammonium ion and glucose on mAb production in suspension and fixed bed hybridoma cultures.

作者信息

Racher A J, Looby D, Griffiths J B

机构信息

PHLS CAMR, Biologics Division, Salisbury, Wiltshire, UK.

出版信息

J Biotechnol. 1993 May;29(1-2):145-56. doi: 10.1016/0168-1656(93)90047-q.

DOI:10.1016/0168-1656(93)90047-q

PMID:7763706

Abstract

Previous work indicated that mAb production by a mouse-mouse hybridoma, grown in a fixed bed of macroporous glass beads with a variable feed glutamine concentration, was correlated only to QvO2. The work reported in this study further investigated the metabolic parameters modulating mAb production using metabolic data from a continuous stirred tank reactor (CSTR) to interpret the behaviour of cells grown in a fixed bed bioreactor (FBR). For a FBR culture grown with a feed glutamine concentration of 3 mmol l-1, QvmAb was correlated to QvO2 and QvGln. However, if the feed glutamine concentration was switched between 1 and 3 mmol l-1, the above relationship did not hold, probably because QvO2 was at or near its maximum value. For both the FBR and CSTR, switches in the feed glutamine concentration suggested that maximum QvmAb values were associated with glucose concentrations above 12.8 mmol l-1 and an ammonium concentration of 2.0-2.5 mmol l-1.

摘要

先前的研究表明，在具有可变进料谷氨酰胺浓度的大孔玻璃珠固定床中生长的小鼠-小鼠杂交瘤产生单克隆抗体（mAb）的情况仅与氧消耗率（QvO2）相关。本研究报告的工作进一步利用来自连续搅拌罐反应器（CSTR）的代谢数据研究了调节mAb产生的代谢参数，以解释在固定床生物反应器（FBR）中生长的细胞的行为。对于以3 mmol l-1的进料谷氨酰胺浓度培养的FBR培养物，单克隆抗体氧消耗率（QvmAb）与氧消耗率（QvO2）和谷氨酰胺消耗率（QvGln）相关。然而，如果进料谷氨酰胺浓度在1至3 mmol l-1之间切换，上述关系则不成立，这可能是因为氧消耗率（QvO2）处于或接近其最大值。对于FBR和CSTR，进料谷氨酰胺浓度的切换表明，最大单克隆抗体氧消耗率（QvmAb）值与高于12.8 mmol l-1的葡萄糖浓度以及2.0 - 2.5 mmol l-1的铵浓度相关。