Placental transfer of125iodinated humanized immunoglobulin G2Δa in the cynomolgus monkey

Autor: Christopher J. Bowman, Mengmeng Wang, Michael J. Potchoiba, Gerhard F. Weinbauer, Denise O'Hara, Natasha R. Catlin, Andrea Z Mitchell, Minlei Zhang
Rok vydání: 2019
Předmět:
Zdroj: Birth Defects Research. 112:105-117
ISSN: 2472-1727
DOI: 10.1002/bdr2.1615
Popis: 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.
Databáze: OpenAIRE
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