FcRn-Dependent Transcytosis of Monoclonal Antibody in Human Nasal Epithelial Cells In Vitro: A Prerequisite for a New Delivery Route for Therapy?

Abstract

Monoclonal antibodies (mAbs) are promising therapies to treat airway chronic inflammatory disease (asthma or nasal polyps). To date, no study has specifically assessed, in vitro, the potential function of neonatal Fc receptor (FcRn) in IgG transcytosis through the human nasal airway epithelium. The objective of this study was to report the in vitro expression and function of FcRn in nasal human epithelium. FcRn expression was studied in an air–liquid interface (ALI) primary culture model of human nasal epithelial cells (HNEC) from polyps. FcRn expression was characterized by quantitative RT-PCR, western blot, and immunolabeling. The ability of HNECs to support mAb transcytosis via FcRn was assessed by transcytosis assay. This study demonstrates the expression of FcRn mRNA and protein in HNEC. We report a high expression of FcRn in the cytosol of ciliated, mucus, and basal cells by immunohistochemistry with a higher level of FcRn proteins in differentiated HNEC. We also proved in vitro transepithelial delivery of an IgG1 therapeutic mAb with a dose–response curve. This is the first time that FcRn expression and mAb transcytosis has been shown in a model of human nasal respiratory epithelium in vitro. This study is a prerequisite for FcRn-dependent nasal administration of mAbs.

MST1 Regulates Neuronal Cell Death via JNK/Casp3 Signaling Pathway in HFD Mouse Brain and HT22 Cells

“…The Western blot analysis was conducted as previously performed in our lab [65,66]. First, the mice were euthanized via giving proper anesthesia and then sacrificed, brains were carefully collected, and, for freezing, tissues were kept on dry ice.…”

Air−Liquid Interface Cultures of the Healthy and Diseased Human Respiratory Tract: Promises, Challenges, and Future Directions

“…[ 26,27 ] Due to the lack of suitable immortalized cell lines of normal nasal tissue, many applications of drug delivery research use primary epithelial cells from nasal brushings or from nasal polyps. [ 28,29 ]…”

“…investigated the ability of a monoclonal antibody to bind the neonatal Fc receptor in human nasal epithelial cells as a potential administration route in asthma‐related chronic rhinosinusitis. [ 29 ] Despite the advantages offered by this alternative source of primary cells, it is important to consider that they have some intrinsic differences in comparison with the bronchial ones that might affect the reliability of the results. It is therefore important to keep in mind the implications of choosing one or the other source of cells.…”

In Translation: FcRn across the Therapeutic Spectrum

“…However, some studies show that FcRn within keratinocytes may facilitate uptake of anti-mitochondrial antibodies, leading to keratinocyte apoptosis and eventual pemphigus vulgaris [ 96 ]. In the nasal epithelium, FcRn levels are sufficiently high to deliver transepithelial IgG1, at least in vitro [ 97 ]. Whether this finding can be leveraged toward nasal delivery of Fc-bearing therapeutics is an ongoing area of investigation.…”