Immunoinformatic Risk Assessment of Host Cell Proteins During Process Development for Biologic Therapeutics

Abstract

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. Graphical Abstract

Host cell protein networks as a novel co‐elution mechanism during protein A chromatography

“…Furthermore, most HCPs may be considered as foreign to the human immune system and may elicit an anti-HCP antibody response. In case of CHO-derived HCPs, however, the mere presence of anti-HCP antibodies might not always have negative consequences, unless the HCPs share sequence similarity with the drug or endogenous proteins or if they induce bystander inflammation (de Zafra et al, 2015;Fischer et al, 2017;Haltaufderhyde et al, 2023).…”

“…Furthermore, most HCPs may be considered as foreign to the human immune system and may elicit an anti‐HCP antibody response. In case of CHO‐derived HCPs, however, the mere presence of anti‐HCP antibodies might not always have negative consequences, unless the HCPs share sequence similarity with the drug or endogenous proteins or if they induce bystander inflammation (de Zafra et al, 2015; Fischer et al, 2017; Haltaufderhyde et al, 2023). Also, the immunogenicity or adjuvanticity risk of HCPs may be influenced by numerous variables, including the HCP concentration, the indication, the dosage and co‐medication as well as the route of administration (de Zafra et al, 2015).…”