Multidimension cultivation analysis by standard and omics methods for optimization of therapeutics production

Julia Gettmann,Anica Lohmeier,Heino Büntemeyer,Christina Timmermann,Oliver Rupp,Thomas Noll,Tobias Thüte,Jennifer Becker,Alexander Goesmann

doi:10.1186/1753-6561-7-s6-p5

Abstract

Background During the last decades Chinese Hamster Ovary (CHO) cells have been extensively used for research and biotechnological applications. About 40% of newly approved glycosylated protein pharmaceuticals are produced in CHO cells today [1]. Despite the increasing relevance of these cells for biopharmaceutical production little is known about effects of intracellular processes on productivity and product quality. In the last years supplementation of serum-free media with insulin more and more replaced by IGF-1 and its analogue LongR was utilized to enhance product titer and quality. To compare the intracellular effects of these two supplements an antibody producing CHO cell line was cultivated in batch mode using insulin, LongR or no growth factor as reference. Subsequently, different omics-techniques were applied to analyze medium and cell samples.

Highlights

During the last decades Chinese Hamster Ovary (CHO) cells have been extensively used for research and biotechnological applications
Cultivation data illustrated that maximal cell density was higher in cultivations with insulin and LongR3 compared to that without growth factor
Glucose consumption and lactate production was slightly higher in cultivations with these supplements but time point of glutamine depletion was similar in all reactors after similar cultivation time (Figure 1A)

Summary

Introduction

During the last decades Chinese Hamster Ovary (CHO) cells have been extensively used for research and biotechnological applications. About 40% of newly approved glycosylated protein pharmaceuticals are produced in CHO cells today [1]. Despite the increasing relevance of these cells for biopharmaceutical production little is known about effects of intracellular processes on productivity and product quality. In the last years supplementation of serum-free media with insulin - more and more replaced by IGF-1 and its analogue LongR3 - was utilized to enhance product titer and quality. To compare the intracellular effects of these two supplements an antibody producing CHO cell line was cultivated in batch mode using insulin, LongR3 or no growth factor as reference. Different omics-techniques were applied to analyze medium and cell samples

Methods

Results

Conclusion