Evaluation of the OSCAR™ system for the production of monoclonal antibodies by CHO-K1 cells
Abstract
Biopharmaceutical production of complex recombinant protein therapeutics currently relies on mammalian cells. The development of high-yielding stable cell lines requires processes of transfection, selection and adaptation. With several technologies available, selection has been most frequently based on dihydrofolate reductase or glutamine synthetase systems, which can be very time-consuming. Due to the pressure to reduce development costs and speed up time to market, new technologies are emerging, as the promising OSCAR expression system that could provide more rapid development of high-yielding stable cell lines than the traditional systems. However, further evaluation of its application in a wider range of cell types and media is still necessary. In this study, application of OSCAR for the transfection of a CHO-K1 cell line with a monoclonal antibody was evaluated. OSCAR was reasonably fast and simple, without negative impact on cell growth characteristics. However, minigene selection was critical, with only pDWM128 working for the cell line assessed. Initial relatively high levels of production decreased significantly in the first few weeks of passing, remaining relatively stable although with low yield thereafter. The results suggest that more work is required to develop methodologies and prove that OSCAR has significant value to the bioproduction industry.
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Other selection systems developed more recently include the OSCAR system, which uses minigene vectors encoding hypoxanthine phosphoribosyltransferase (HPRT), essential for purine synthesis.
“Other selection systems have been developed more recently, such as the OSCAR™ system from the University of Edinburgh, that uses minigene vectors encoding the hypoxanthine phosphoribosyltransferase (HPRT), essential for purine synthesis (Melton et al., 2001;Costa et al., 2012).”
From Therapeutic glycoprotein production in mammalian cells (2017) · cites this paper as Costa et al., 2012
Cites
Guidelines to cell engineering for monoclonal antibody production
Rita Costa, A., Elisa Rodrigues, M., Henriques, M., Azeredo, J., & Oliveira, R. (2010) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2009.10.002 · Cited by 178 · see citing works
Self-citationAssessment of cell engineering strategies for improved therapeutic protein production in CHO cells
Mohan (2008) · Biotechnology Journal · doi:10.1002/biot.200700249 · Cited by 102 · see citing works
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Therapeutic glycoprotein production in mammalian cells
Lalonde, M.-E., & Durocher, Y. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.04.028 · Cited by 296 · see citing works
- Authors
- Costa, A. R., Rodrigues, M. E., Henriques, M., Melton, D., Cunnah, P., Oliveira, R., & Azeredo, J.
- Affiliations
- Institute for Biotechnology and Bioengineering (PT)
- Edinburgh Cancer Research (GB)
- Corresponding author
- Henriques, Mariana
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 430
- Issue
- 1-2
- Pages
- 42-46
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2063968047
- Cited by
- 12
- References
- 2
- Citations by year
- 2024: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 1 · 2013: 4 · 2012: 2
- FWCI
- 0.77
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundação para a Ciência e a Tecnologia
- Agência Nacional de Inovação
- Fundació Catalana de Trasplantament (SFRH/BD/46660/2008, SFRH/BD/46661/2008)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Viral Infectious Diseases and Gene Expression in Insects
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Transgenic Plants and Applications
- Keywords
- monoclonal antibodies, CHO-K1 cells, transfection, recombinant protein expression
- MeSH terms
- Aminopterin, Animals, Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, Cricetulus, Genetic Vectors, Cricetinae, Hypoxanthine Phosphoribosyltransferase, Recombinant Proteins, Thymidine, Time Factors, Transfection, CHO Cells, Hypoxanthine, Cell Proliferation
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