FcRn expression in cancer: Mechanistic basis and therapeutic opportunities

Abstract

There is an urgent need to identify new cellular targets to expand the repertoire, potency and safety of cancer therapeutics. Neonatal Fc Receptor (FcRn)-driven cellular recycling plays a predominant role in the prolonged serum half-life of human serum albumin (HSA) and immunoglobulin G (IgG) exploited in long-acting cancer drug designs. FcRn-mediated HSA and IgG uptake in epithelial cells and dendritic cell antigen presentation offers new therapeutic opportunities beyond half-life extension. Altered FcRn expression in solid tumours accounting for HSA catabolism or recycling supports a role for FcRn in tumour metabolism and growth. This review addresses the mechanistic basis for different FcRn expression profiles observed in cancer and exploitation for targeted drug delivery. Furthermore, the review highlights FcRn-mediated immunosurveillance and immune therapy. FcRn offers a potential attractive cancer target but in-depth understanding of role and expression profiles during cancer pathogenesis is required for tailoring targeted drug designs.

Keywords: Albumin-drug designs; Antibody-drug designs; Cancer immunotherapy; Neonatal Fc Receptor; Targeted cancer therapy; Tumour metabolism.