Abstract:
:Antibody-like biopharmaceuticals cross the placenta by utilizing existing transport pathways (e.g., FcRn receptor). There are limited data evaluating this transfer during organogenesis in any species. Understanding placental transfer of antibody-like biopharmaceuticals can help to predict risk of developmental toxicity across species, including humans. To complement previously published placental transfer data in the rat with humanized IgGΔ2 (hIgG2), the timing and magnitude of transfer in the cynomolgus monkey and embryo/fetal biodistribution of maternally administered 125 I-radiolabeled hIgG2 was quantified on gestation days (GD) 35, 40, 50, 70, and 140 using gamma counting and whole body autoradiography 24 hr following intravenous injection. Chorioallantoic placental tissues were collected at all time points for Western Blot analysis with anti-FcRn antibody. Maternally administered 125 I-hIgG2 was found in embryo/fetal tissues at all time points, including organogenesis. Embryo/fetal plasma 125 I-hIgG2 concentration increased during gestation, but only slightly up to GD 70 in embryo/fetal tissues, with hIgG2 tissue concentrations generally similar between GD70 and 140. The embryo/fetal:maternal 125 I-hIgG2 plasma concentration ratio was approximately 2.3 fold higher on GD 140, in comparison to ratios on GD 40. Importantly, placental FcRn protein expression was confirmed at all timepoints. These data demonstrate placental transfer of hIgG2 in a nonhuman primate model, and at levels comparable to the rat model, raising the potential for adverse developmental outcomes by direct antibody binding to biological targets.
journal_name
Birth Defects Resjournal_title
Birth defects researchauthors
Catlin NR,Mitchell AZ,Potchoiba MJ,O'Hara DM,Wang M,Zhang M,Weinbauer GF,Bowman CJdoi
10.1002/bdr2.1615subject
Has Abstractpub_date
2020-01-01 00:00:00pages
105-117issue
1issn
2472-1727journal_volume
112pub_type
杂志文章abstract::The aerodigestive and communicative behaviors of anencephalic and hydranencephalic patients are assessed from literature sources and are compared with documented neural structures present in the brainstem, subcortical, and cortical regions of the brain. Much of the data analyzed corroborate previous neurological studi...
journal_title:Birth defects research
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journal_title:Birth defects research
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journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1203
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journal_title:Birth defects research
pub_type: 杂志文章
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journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1863
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journal_title:Birth defects research
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doi:10.1002/bdra.23596
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journal_title:Birth defects research
pub_type: 杂志文章
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journal_title:Birth defects research
pub_type: 杂志文章
doi:10.1002/bdr2.1461
更新日期:2019-04-15 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章,评审
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更新日期:2017-06-01 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章
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journal_title:Birth defects research
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journal_title:Birth defects research
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journal_title:Birth defects research
pub_type: 杂志文章
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更新日期:2017-11-01 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章,评审
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更新日期:2020-07-15 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章
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更新日期:2019-11-01 00:00:00
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journal_title:Birth defects research
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更新日期:2017-06-01 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章
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更新日期:2017-11-01 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章
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更新日期:2018-12-01 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章
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更新日期:2019-07-01 00:00:00
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journal_title:Birth defects research
pub_type: 杂志文章,评审
doi:10.1002/bdr2.1180
更新日期:2017-12-01 00:00:00