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 ¹²⁵I‐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 ¹²⁵I‐hIgG2 was found in embryo/fetal tissues at all time points, including organogenesis. Embryo/fetal plasma ¹²⁵I‐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 ¹²⁵I‐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.

中文翻译：

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食蟹猴中125碘化人源化免疫球蛋白G2Δa的胎盘转移。

抗体样生物药物通过利用现有的转运途径（例如FcRn受体）穿过胎盘。在任何物种的器官发生过程中，评估这种转移的数据有限。了解抗体样生物药物的胎盘转移可以帮助预测包括人类在内的整个物种的发育毒性风险。为了补充人源化IgGΔ2（hIgG2）在大鼠中先前发布的胎盘转移数据，母体给予食蟹猕猴的转移时间和幅度以及胚胎/胎儿的生物分布¹²⁵静脉注射后24小时，使用γ计数和全身放射自显影技术在孕期（GD）35、40、50、70和140天对I放射性标记的hIgG2进行定量。在所有时间点收集绒毛膜胎盘组织，以抗FcRn抗体进行Western Blot分析。在包括器官发生在内的所有时间点，在胚胎/胎儿组织中发现母体给予的¹²⁵ I-hIgG2。胚胎/胎儿血浆¹²⁵ I-hIgG2浓度在妊娠期间增加，但在胚胎/胎儿组织中仅略微升高至GD 70，hIgG2组织的浓度通常在GD70和140之间。胚胎/胎儿：母体¹²⁵与GD 40的比率相比，GD 140的I-hIgG2血浆浓度比率大约高2.3倍。重要的是，在所有时间点均证实了胎盘FcRn蛋白表达。这些数据证明了hIgG2在非人类灵长类动物模型中的胎盘转移，其水平与大鼠模型相当，通过直接抗体与生物靶标的结合提高了不良发育结果的可能性。