Kirk Haltaufderhyde, Brian J Roberts, Sundos Khan, Frances Terry, Christine M Boyle, Mitchell McAllister, William Martin, Amy Rosenberg, Anne S De Groot
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Immunoinformatic Risk Assessment of Host Cell Proteins During Process Development for Biologic Therapeutics.
The 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.
期刊介绍:
The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including:
· Drug Design and Discovery
· Pharmaceutical Biotechnology
· Biopharmaceutics, Formulation, and Drug Delivery
· Metabolism and Transport
· Pharmacokinetics, Pharmacodynamics, and Pharmacometrics
· Translational Research
· Clinical Evaluations and Therapeutic Outcomes
· Regulatory Science
We invite submissions under the following article types:
· Original Research Articles
· Reviews and Mini-reviews
· White Papers, Commentaries, and Editorials
· Meeting Reports
· Brief/Technical Reports and Rapid Communications
· Regulatory Notes
· Tutorials
· Protocols in the Pharmaceutical Sciences
In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.