The neonatal Fc receptor (FcRn) represents a transport system with the potential to facilitate absorption of biologics across the gastrointestinal barrier. How biologics interact with FcRn to enable their gastrointestinal absorption, and how these interactions might be optimized in a biological therapeutic are not well understood. Thus, we studied the absorption of Fc molecules from the intestine using three IgG₄-derived Fc variants with different, pH-dependent FcRn binding and release profiles. Using several different intestinal models, we consistently observed that FcRn binding affinity correlated with transcytosis. Our findings support targeting FcRn to enable intestinal absorption of biologics and highlight additional strategic considerations for future work.

新生儿 Fc 受体 (FcRn) 是一种转运系统，具有促进生物制剂跨胃肠屏障吸收的潜力。生物制剂如何与 FcRn 相互作用以使其胃肠吸收，以及如何在生物治疗中优化这些相互作用尚不清楚。因此，我们使用具有不同的、pH 依赖性 FcRn 结合和释放特征的三种 IgG ₄衍生的 Fc 变体研究了 Fc 分子从肠道的吸收。使用几种不同的肠道模型，我们一致观察到 FcRn 结合亲和力与转胞吞作用相关。我们的研究结果支持靶向 FcRn 以实现生物制剂的肠道吸收，并强调未来工作的其他战略考虑。