Abstract
AbstractThe identification and removal of host cell proteins (HCPs) from biologic products is a critical step in drug development. Despite recent improvements to purification processes, biologics such as monoclonal antibodies, enzyme replacement therapies, and vaccines that are manufactured in a range of cell lines and purified using diverse processes may contain HCP impurities, making it necessary for developers to identify and quantify impurities during process development for each drug product. HCPs that contain sequences that are less conserved with human homologs may be more immunogenic than those that are more conserved. We have developed a computational tool, ISPRI-HCP, that estimates the immunogenic potential of HCP sequences by evaluating and quantifying T cell epitope density and relative conservation with similar T cell epitopes in the human proteome. Here we describe several case studies that support the use of this method for classifying candidate HCP impurities according to their immunogenicity risk.
Graphical Abstract
Publisher
Springer Science and Business Media LLC
Reference85 articles.
1. (2022) Fact Sheet: FDA at a Glance. In: FDA U.S. Food and drug administration. https://www.fda.gov/about-fda/fda-basics/fact-sheet-fda-glance. Accessed 13 Feb 2023
2. BioSpace (2022) Biologics Market Size to Hit USD 719.94 Billion by 2030. In: BioSpace. https://www.biospace.com/article/biologics-market-size-to-hit-usd-719-94-billion-by-2030-/. Accessed 13 Feb 2023
3. Senior M. Fresh from the biotech pipeline: fewer approvals, but biologics gain share. Nat Biotechnol. 2023;41:174–82. https://doi.org/10.1038/s41587-022-01630-6.
4. Vanderlaan M, Zhu-Shimoni J, Lin S, Gunawan F, Waerner T, Van Cott KE. Experience with host cell protein impurities in biopharmaceuticals. Biotechnol Prog. 2018;34:828–37.
5. Park JH, Jin JH, Lim MS, An HJ, Kim JW, Lee GM. Proteomic Analysis of Host Cell Protein Dynamics in the Culture Supernatants of Antibody-Producing CHO Cells. Sci Rep. 2017;7:44246.
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献