Abstract
Recombinant antibodies are rapidly developing therapeutic agents; approximately 40 novel antibody molecules enter clinical trials each year, most of which are produced from Chinese hamster ovary (CHO) cells. However, one of the major bottlenecks restricting the development of antibody drugs is how to perform high-level expression and production of recombinant antibodies. The high-efficiency expression and quality of recombinant antibodies in CHO cells is determined by multiple factors. This review provides a comprehensive overview of several state-of-the-art approaches, such as optimization of gene sequence of antibody, construction and optimization of high-efficiency expression vector, using antibody expression system, transformation of host cell lines, and glycosylation modification. Finally, the authors discuss the potential of large-scale production of recombinant antibodies and development of culture processes for biopharmaceutical manufacturing in the future.
Highlights
In recent years, recombinant antibody drugs are emerging with the rapid development of modern molecular biology technology as well as in-depth exploration on the three-dimensional structure and mechanism of action of antibody molecules
Expression of GnT-III: Studies have shown that the bisected glycosylated epidermal growth factor receptor (EGFR) monoclonal antibody is prepared by introducing the GnT-III gene and highly expresses bisecting acetylglucosamine residues; this strategy can increase the antibody-dependent cell-mediated cytotoxicity (ADCC) activity by 3 times and increase the anti-proliferative activity by 1.36 times, and almost no α-Gal was detected
With the development and application of proteomics technology, the development of large-scale culture of animal cells for antibody drug production has devolved from the simple optimization of some process parameters to the recent omics research, e.g., transcriptomics, proteomics, metabolomics, glycomics, and fluxomics
Summary
Recombinant Antibody Production and Quality in Chinese Hamster Ovary Cells. Recombinant antibodies are rapidly developing therapeutic agents; approximately 40 novel antibody molecules enter clinical trials each year, most of which are produced from Chinese hamster ovary (CHO) cells. One of the major bottlenecks restricting the development of antibody drugs is how to perform high-level expression and production of recombinant antibodies. The high-efficiency expression and quality of recombinant antibodies in CHO cells is determined by multiple factors. This review provides a comprehensive overview of several state-of-the-art approaches, such as optimization of gene sequence of antibody, construction and optimization of high-efficiency expression vector, using antibody expression system, transformation of host cell lines, and glycosylation modification. The authors discuss the potential of large-scale production of recombinant antibodies and development of culture processes for biopharmaceutical manufacturing in the future
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