Evaluation of Potential Antigenicity of Active-Site-Inhibited Recombinant Human FVIIa (FFR-rFVIIa) in an Immune-Tolerant Rat Model
| Autor: | Annemarie Kristensen, Else Marie Nicolaisen, Hanne I Kristensen, Ulla Hedner |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
Antigenicity Recombinant Fusion Proteins medicine.medical_treatment Intraperitoneal injection Immunization Secondary Antibodies Heterophile Enzyme-Linked Immunosorbent Assay Factor VIIa Pharmacology Amino Acid Chloromethyl Ketones law.invention Immune tolerance Immune system Species Specificity Antigen law Antigens Heterophile Immune Tolerance medicine Animals Humans Enzyme Inhibitors Rats Wistar Binding Sites biology business.industry Hematology Rats Specific Pathogen-Free Organisms Animals Newborn Enzyme inhibitor Injections Intravenous Models Animal Immunology biology.protein Recombinant DNA Female Immunization Antibody business Injections Intraperitoneal |
| Zdroj: | University of Copenhagen |
| ISSN: | 2567-689X 0340-6245 |
| Popis: | SummaryRecombinant human FVIIa (rFVIIa) was inactivated by coupling Phe-Phe-Arg-CO- (FFR) covalently to the active site of the enzyme. To test the chemically-modified human protein for potential antigenicity prior to clinical trial an immune-tolerant rat model was established. Intraperitoneal injection of the parent compound, human rFVIIa, within 30 h after birth, followed by repeated subcutaneous challenge with rFVIIa in Freunds incomplete adjuvant resulted in 79% non-responding rats at day 32. Monthly subcutaneous challenge showed that the induced tolerance was stable over the 3 months study period in 80% of the rats. The clinically relevant route, intravenous administration, was used for evaluating the potential antigenicity of FFR-rFVIIa. Repeated intravenous administration of different dosages of FFR-rFVIIa did not break tolerance, indicating that FFR-rFVIIa might not be antigenic, for a limited number of intravenous administrations in a clinical setting. |
| Databáze: | OpenAIRE |
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