Misfolded cellular prion protein (PrPC) disease-specific epitope (PrPC DSE)

The cellular prion protein (PrPC) is a glycosylphosphatidylinositol (GPI)-anchored cell surface glycoprotein encoded by the PRNP gene. While primarily known for its role in neurodegenerative diseases, PrPC is frequently overexpressed in various malignancies, including gastric, pancreatic, and breast cancers, where it promotes tumor progression and multi-drug resistance (Atkinson et al., 2016). In the tumor microenvironment, PrPC can adopt misfolded or aberrant conformations that expose disease-specific epitopes (DSEs), which are unique molecular signatures not present on the normally folded protein in healthy tissues (ProMIS Neurosciences). These DSEs serve as highly selective therapeutic targets, allowing for the development of monoclonal antibodies that can distinguish between malignant cells and healthy neurons. By binding to these epitopes, therapeutic agents can trigger immune-mediated destruction of cancer cells or inhibit signaling pathways that drive the epithelial-mesenchymal transition and metastasis (Li et al., 2014). This approach aims to overcome the safety challenges of targeting a protein that is widely expressed in the central nervous system by focusing exclusively on the pathological conformation.

Other names

PrPCCD230Prion proteinPRNPMisfolded PrPCancer-associated prion protein

Selective binding to misfolded conformations of PrPC on cancer cells to trigger immune-mediated cell death or inhibit pro-survival signaling pathways.