fulltext.study @t Gmail

Efficient folding/assembly in Chinese hamster ovary cells is critical for high quality (low aggregate content) of secreted trastuzumab as well as for high production: Stepwise multivariate regression analyses

Paper ID Volume ID Publish Year Pages File Format Full-Text
20356 43170 2014 8 PDF Available
Title
Efficient folding/assembly in Chinese hamster ovary cells is critical for high quality (low aggregate content) of secreted trastuzumab as well as for high production: Stepwise multivariate regression analyses
Abstract

When developing cell culture processes for therapeutic antibodies, the low content of aggregated proteins is the most critical because administering aggregated antibody molecules might result in adverse effects such as immunogenicity. To characterize cells with high productivity and quality, we determined factors that are closely related to antibody titer, which is a productivity indicator, and the area percentage of high molecular weight species in cultivated media, which is equivalent to aggregate content and is used as a quality indicator. We examined the factors influencing antibody titer and aggregate content using various data from 28 cell lines throughout their culture periods from growth to death phases. Our study using correlation analysis revealed that statistically significant correlations between factors and indicators changes with sampling points, hence we thought that various factors would influence each indicator simultaneously. To understand the relationship between these factors and titer/aggregates contents, we performed stepwise multiple linear regression analyses and deduced a multiple linear model for each indicator. The titer was found to positively associate with specific growth rate and specific production rate and negatively with intracellular heavy chain content. The aggregate content was found to positively associate with protein disulfide isomerase mRNA level and negatively with light chain secreted into culture media, specific production rate, intracellular light chain content, and specific growth rate. Our observations suggest that correct and efficient assembling and/or folding of an antibody molecule in an endoplasmic reticulum are important for high titer and low aggregates contents.

Keywords
Therapeutic antibody; Antibody productivity; Antibody quality; Cell line; Antibody aggregate; Chinese hamster ovary cell; Endoplasmic reticulum stress; Protein disulfide isomerase; Heavy chain binding protein; Stepwise multiple linear regression
First Page Preview
Efficient folding/assembly in Chinese hamster ovary cells is critical for high quality (low aggregate content) of secreted trastuzumab as well as for high production: Stepwise multivariate regression analyses
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us
Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Bioscience and Bioengineering - Volume 118, Issue 2, August 2014, Pages 223–230
Authors
, , , , ,
Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us