Misfolded prion protein disease-specific epitope (PrP-DSE)

The misfolded prion protein disease-specific epitope (DSE) is a conformational target found on the surface of various cancer cells, representing a pathologically altered state of the cellular prion protein (PrP-C). While PrP-C is a normal cell-surface glycoprotein involved in cell signaling and neuroprotection, it is frequently overexpressed in malignancies such as ovarian, gastric, and pancreatic cancers. In the tumor microenvironment, PrP-C can undergo misfolding, exposing cryptic epitopes like the YYR (tyrosine-tyrosine-arginine) motif that are normally buried within the protein's native structure. These exposed DSEs act as selective biomarkers and therapeutic targets, as they are absent on healthy cells. Misfolded PrP on cancer cells functions as a scaffold that promotes tumor proliferation, metastasis, and resistance to chemotherapy by activating oncogenic pathways such as PI3K-Akt and MEK-ERK. Therapeutic strategies, notably those developed by ProMIS Neurosciences (formerly Amorfix), utilize monoclonal antibodies like AMF-1c-120 to selectively target these epitopes, enabling the delivery of cytotoxins or the induction of immune-mediated cell death while sparing normal tissues.

Other names

YYR epitopeYML epitopePrP-Sc-like epitopeMisfolded PrP-CAMF-1c-120 targetMDEYSNQNN epitopePrion protein disease-specific epitope

Selective binding to conformational epitopes exposed only on misfolded prion protein, leading to targeted cell death via antibody-dependent cellular cytotoxicity (ADCC) or delivered toxins, and inhibition of oncogenic signaling pathways.