Validation and Improvement of ISPRI-HCP: An Innovative Platform for Immunogenicity Risk Assessment of Process-related Protein Impurities
Validation and Improvement of ISPRI-HCP: An Innovative Platform for Immunogenicity Risk Assessment of Process-related Protein Impurities
批准号:
10603538
负责人:
Kirk Donald Haltaufderhyde
金额:
$29.99万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
已结题
起止时间:
2023-08-01 至 2024-07-31
关键词:
AddressAdenovirusesAlgorithmsAnnexinsAntibodiesAntigensBiologicalBiological AssayBiological ProductsCOVID-19 vaccineCell LineCellsCellular AssayChinese HamsterChinese Hamster Ovary CellClassificationDNADataEffectivenessEnzyme-Linked Immunosorbent AssayEpitopesEvaluationExcisionGRP78 geneGSTP1 geneGoalsHigh Pressure Liquid ChromatographyHuman GenomeImmune responseIn VitroIndividualInvestigationLicensingLinkMeasuresMethodsModificationMonoclonal AntibodiesOvaryPeptidesPerformancePeripheral Blood Mononuclear CellPharmaceutical PreparationsPhaseProcessProcess AssessmentProductionProteinsPublishingRecombinant ProteinsResearchResearch PersonnelRiskRisk AssessmentSafetySequence AnalysisSmall Business Innovation Research GrantSpeedSystemT-LymphocyteT-Lymphocyte EpitopesTestingThrombocytopeniaVaccinesValidationViral ProteinsViral VectorWestern Blottingadenovirus penton proteincell typedensitydrug developmentdrug efficacyexperimental studyflexibilityhigh risk populationimmunogenicimmunogenicityimprovedin silicoinnovationmanufacturemedication safetynovelprogramsrare conditionsulfated glycoprotein 2thrombotictooltwo-dimensionalvaccine developmentvaccine formulationvaccine safetyvector vaccineweb-based tool
中文摘要
摘要
英文摘要
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.
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