'Simulect' as a model compound for assessing placental transfer of monoclonal antibodies in minipigs
| Autor: | Adam Hey, Céline Pique, Anthony M. DeLise, Edward Marsden, Marilyn Hill, Claudio Calonder, Anette B. Grossi |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Amniotic fluid medicine.drug_class Swine Monoclonal antibody Toxicology Andrology 03 medical and health sciences Basiliximab In vivo Pregnancy Placenta Medicine Animals Maternal-Fetal Exchange Fetus biology business.industry Amniotic Fluid Fetal Blood 030104 developmental biology medicine.anatomical_structure Monoclonal biology.protein Gestation Swine Miniature Female Antibody business Immunosuppressive Agents |
| Zdroj: | Reproductive Toxicology. 64:26 |
| ISSN: | 0890-6238 |
| DOI: | 10.1016/j.reprotox.2016.06.055 |
| Popis: | The aim of this study was to directly test and measure in vivo, if placental transfer of monoclonal antibodies takes place in pregnant Gottingen Minipigs to assess their suitability for reproductive assessment of therapeutic monoclonal antibodies. Simulect®, an approved anti CD25 (anti IL-2 receptor alpha) chimeric monoclonal IgG1 antibody, was used as a model monoclonal antibody. Maternal systemic exposure and potential placental transfer of Simulect® to fetuses were investigated following 4 weekly bolus intravenous administration of 5.0 mg/kg from gestation day (GD) 79 or 80 (e.g GD 79, 86, 93 and 100) and with terminal Caesarean section on GD 108 or GD 109 respectively. Results clearly showed exposure in maternal animals, detectable compound in the amniotic fluid from one out of 9 maternal animals, but no exposure in fetuses confirming absence of placental transfer of the selected model antibody Simulect® in minipigs. The absence of Simulect® in the fetuses further supports that the presence of Simulect® in the amniotic fluid in one maternal animal was likely due to contamination with maternal blood during sampling. The demonstrated absence of fetal exposure clearly indicates that, the minipig is not a suitable species for conduct of reproductive toxicity studies with monoclonal antibodies. |
| Databáze: | OpenAIRE |
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