Despite ongoing process improvements in manufacturing, Host cell protein (HCP) process impurities remain a substantial risk for biological products. Even at low levels, residual HCPs can induce a detrimental immune response, compromising the safety and efficacy of a biologic. Consequently, advanced-stage clinical trials have been cancelled due to the identification of antibodies against HCPs. From a safety, efficacy and regulatory standpoint, the presence of these impurities should be assessed and addressed early in the product characterization process.
As a solution, EpiVax has developed an efficient, internet-based interface for immunogenicity screening of host cell proteins. The Interactive Screening and Protein Reengineering Interface for Host Cell Proteins (ISPRI-HCP) is a secure, online work environment, supported by EpiVax’s proprietary EpiMatrix and JanusMatrix algorithms and can be used to evaluate the immunogenic potential of contaminant host cell proteins such as Chinese Hamster Ovary (CHO), as well as other expression systems. Our toolkit enables the rapid assessment of the potential for anti-HCP antibody generation directly from your HCP sequences to ultimately identify those HCPs that represent a potential risk for immunogenicity and should be removed, while also identifying those that are “Human-like” and likely to be tolerated if administered with the drug.
Protein Expression Systems are commonly used in the manufacturing of protein therapeutics and impurities from these host cell proteins can present an additional immunogenicity risk for developers to consider in addition to screening the immunogenic potential of the biologic sequence itself.
Here’s a list of some common expression systems we often come across in our work:
- Chinese Hamster Ovary Cells (CHO-K1 and others)
- HEK-293 Cells – human embryonic kidney cells
- PER.C6 Cells – human embryonic retinal cells
- Vero Cells – kidney cells derived from monkey
- Bacteria (E. coli)
- Insect Cells
Many expression systems are human or mammalian cell lines, with CHO being an especially popular choice. Fortunately, because CHO, Vero Cells (Monkey), and other cell lines are mammalian in origin, many of the epitopes found in host cell impurities from these expression systems are similar to those found in human proteins and thus less likely to drive an adverse immune response. By utilizing T cell cross-reactivity analysis from JanusMatrix, the ISPRI-HCP tool can identify the number of more dangerous (expression system unique) epitopes found within a potential contaminant.
While there are certain benefits to using E. coli and other non-mammalian cell lines as an expression system, HCP impurities from these cell lines may carry more immunogenic risk. Epitopes present in these contaminant sequences will likely be non-human and could potentially drive an inflammatory immune response in humans.
Application of the ISPRI-HCP tool can help to enhance the quality and value of your biomanufacturing processes, serving as computational complement to existing experimental approaches for the assessment of risk associated with HCP process impurities.