ArticleJournal of pharmaceutical sciences2006
Influence of aggregation on immunogenicity of recombinant human Factor VIII in hemophilia A mice.
Article in Journal of pharmaceutical sciences, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 94 citations in OpenAlex.
- A Deletion Variant of Human Factor VIII Displaying Low Immunogenicity in a Murine Model of Hemophilia A.International journal of molecular sciences · 2025Article
- Highly variable aggregation and glycosylation profiles and their roles in immunogenicity to protein-based therapeutics.Journal of pharmaceutical sciences · 2025Review
- A High Threshold of Biotherapeutic Aggregate Numbers is Needed to Induce an Immunogenic Response In Vitro, In Vivo, and in the Clinic.Pharmaceutical research · 2024Article
- Immunogenicity of Protein Pharmaceuticals.Journal of pharmaceutical sciences · 2019Review
- N-linked glycosylation modulates the immunogenicity of recombinant human factor VIII in hemophilia A mice.Haematologica · 2018Article
- Effect of growth hormone and IgG aggregates on dendritic cells activation and T-cells polarization.Immunology and cell biology · 2017Article
- Metal-mediated protein oxidation: applications of a modified ELISA-based carbonyl detection assay for complex proteins.Pharmaceutical research · 2015Article
- The Role of Aggregates of Therapeutic Protein Products in Immunogenicity: An Evaluation by Mathematical Modeling.Journal of immunology research · 2015Article
- Reduction of the C191-C220 disulfide of α-chymotrypsinogen A reduces nucleation barriers for aggregation.Biophysical chemistry · 2014Article
- Influence of the valine zipper region on the structure and aggregation of the basic leucine zipper (bZIP) domain of activating transcription factor 5 (ATF5).Molecular pharmaceutics · 2012Article
- Highly aggregated antibody therapeutics can enhance the in vitro innate and late-stage T-cell immune responses.The Journal of biological chemistry · 2012Article
- Protein particulate detection issues in biotherapeutics development--current status.AAPS PharmSciTech · 2012Review
- Native-like aggregates of factor VIII are immunogenic in von Willebrand factor deficient and hemophilia a mice.Journal of pharmaceutical sciences · 2012Article
- Distinct aggregation mechanisms of monoclonal antibody under thermal and freeze-thaw stresses revealed by hydrogen exchange.Pharmaceutical research · 2012Article
- Classification and characterization of therapeutic antibody aggregates.The Journal of biological chemistry · 2011Article
- A new approach to explore the impact of freeze-thaw cycling on protein structure: hydrogen/deuterium exchange mass spectrometry (HX-MS).Pharmaceutical research · 2011Article
- Phosphatidylserine reduces immune response against human recombinant Factor VIII in Hemophilia A mice by regulation of dendritic cell function.Clinical immunology (Orlando, Fla.) · 2011Article
- Phosphatidylinositol containing lipidic particles reduces immunogenicity and catabolism of factor VIII in hemophilia a mice.The AAPS journal · 2010Article
- A role for thrombin in the initiation of the immune response to therapeutic factor VIII.Blood · 2009Article
- Factor VIII inhibitors: risk factors and methods for prevention and immune modulation.Clinical reviews in allergy & immunology · 2009Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Recombinant human factor VIII (rFVIII), a multidomain glycoprotein is used in replacement therapy for treatment of hemophilia A. Unfortunately, 15%-30% of the treated patients develop inhibitory antibodies. The pathogenesis of antibody development is not completely understood. The presence of aggregated protein in formulations is generally believed to enhance the immune response. rFVIII has a tendency to aggregate but the effect of such aggregation on the immunogenicity of rFVIII is not known. We have, therefore, characterized aggregated rFVIII produced by thermal stress and evaluated its effect on the immunogenicity of rFVIII in hemophilia A mice. Aggregated rFVIII alone and mixtures of rFVIII with aggregated rFVIII were less immunogenic than native rFVIII. In vitro Th-cell proliferation studies and cytokine analyses conducted on splenocytes obtained from immunized animals suggest that aggregated rFVIII behaves as a unique antigen compared to native monomeric rFVIII. The antigenic properties of the aggregated and native rFVIII were compared using ELISAs (epitope availability) and cathepsin-B (an antigen processing enzyme) digestion. The data suggest significant differences in the antigenic properties of rFVIII and aggregated rFVIII. Overall it appears that aggregated rFVIII does not enhance the immunogenicity (inhibitor development) of rFVIII in hemophilia A mice but rather acts as a distinct antigen.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.