Validation and Improvement of ISPRI-HCP: An Innovative Platform for Immunogenicity Risk Assessment of Process-related Protein Impurities

ABSTRACT The identification and removal of process-related protein impurities (PRPI) from biologic products is a critical step in drug development. Despite recent improvements in the purification and processing of biologics, the presence of immunogenic PRPI continue to raise concerns about drug safety and efficacy. We propose an innovative approach for assessing immunogenicity risk of PRPI using our existing ISPRI-HCP platform. ISPRI- HCP stands apart from conventional methods by utilizing a T cell approach based on the T cell epitope count and density. We hypothesize that ISPRI-HCP can accurately classify candidate PRPI impurities according to their immunogenicity risk. To test this hypothesis, we will determine the T cell immunogenicity of 8 frequently found PRPI from Chinese Hamster Ovary (CHO) cell expression systems and 5 PRPI from adenoviral vaccines. The selected PRPI classified by ISPRI-HCP cover a wide range of immunogenicity risk. Peptide pools comprised of T cell epitopes of the selected proteins will be prepared and tested for their ability to induce antigen-specific INF-g secreting T cells in assays using peripheral blood mononuclear cells (PBMCs). The overall goal of this study is to provide proof-of-concept and further improve ISPRI-HCP as a platform for predicting the immunogenicity risk of PRPI.