CHO Protein Predicted Immunogenicity (CHOPPI) integrates a number of data sources — genome, transcriptome, secretome, and immunome — to identify immunogenicity risks from host contaminant proteins (HCPs) in Chinese Hamster Ovary (CHO)-based protein production. CHOPPI was developed in a collaboration between Dartmouth College, EpiVax, Inc. and the Institute for Immunology and Informatics (iCubed), and is driven by the EpiMatrix T cell epitope predictor. A preliminary description of the underlying method was presented at the Immunoinformatics and Computational Immunology Workshop, 2012; a journal publication is in preparation.
Despite high quality standards and continual process improvements in manufacturing, host cell protein (HCP) process impurities remains 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. To enable earlier and rapid assessment of the risks in CHO-based protein production of residual CHO protein
impurities (CHOPs), we have developed a web tool called CHOPPI, for CHO Protein Predicted Immunogenicity. CHOPPI integrates information regarding the possible presence of CHOPs (expression and secretion) with characterizations of their immunogenicity (T cell epitope count and density, and relative conservation with human counterparts).CHOPPI can generate a report for a specified CHO protein (e.g., identified from proteomics or immunoassays) or characterize an entire specified subset of the CHO genome (e.g., filtered based on confidence in transcription and similarity to human proteins). The ability to analyze potential CHOPs at a genomic scale provides a baseline to evaluate relative risk. CHOPPI can identify clear differences in immunogenicity risk among previously validated CHOPs, as well as identify additional ‘risky’ CHO proteins that may be expressed during production and induce a detrimental immune response upon delivery. CHOPPI is a powerful tool that provides a valuable computational complement to existing experimental approaches for CHOP risk assessment and can focus experimental efforts in the most important directions.
CHOPPI is available and free for academic users, and is subject to a registration step to ensure appropriate use. For adaptations to other host cell lines and for use by commercial entities or any other questions about CHOPPI, please contact Dr. Annie De Groot at firstname.lastname@example.org.
CHOPPI is a web-based immunoinformatics tool for assessing the immunogenicity risk of CHO proteins (CHOPs). These process-related impurities may contribute to immune responses against biologics. CHOPPI users can analyze individual CHOPs or filter the entire CHO genome for immunogenic potential. CHOPPI also characterizes similarity with human proteins at the T cell epitope level, since CHOPs that are similar but not identical to human in terms of epitope content may elicit unfavorable immune responses.