Mucin 5AC (MUC5AC) tumor-specific NPC-1 epitope (MUC5AC NPC-1 epitope)

Mucin 5AC (MUC5AC) is a high-molecular-weight, gel-forming glycoprotein primarily expressed in the gastric and tracheobronchial mucosa, where it protects epithelial cells from environmental insults (UniProt P35221). In various cancers, particularly pancreatic and colorectal adenocarcinomas, MUC5AC is aberrantly expressed and undergoes post-translational modifications that expose unique, tumor-specific epitopes such as NPC-1 (Arlen et al., 2012, PubMed: 22415316). This epitope is the target of the chimeric monoclonal antibody NPC-1C, also known as NEO-102, which was derived from a screen of patients immunized with a colorectal cancer vaccine (ClinicalTrials.gov: NCT01934712). By binding specifically to the NPC-1 epitope on malignant cells, therapeutic antibodies can trigger immune-mediated destruction via antibody-dependent cellular cytotoxicity (ADCC) while minimizing damage to healthy tissues. This target represents a promising avenue for selective immunotherapy in gastrointestinal malignancies where traditional MUC5AC expression might otherwise limit the therapeutic window. Clinical studies have evaluated NPC-1C both as a monotherapy and in combination with chemotherapy for refractory pancreatic and colorectal cancers (Precision Biologics). The specificity of the NPC-1 epitope to tumor tissue is a critical factor in its development as a therapeutic target, aiming to overcome the toxicity associated with targeting widely expressed mucins.

Other names

MUC5ACMucin 5AC, oligomeric mucus/gel-formingNPC-1C antigenNEO-102 antigenGastric mucinTracheobronchial mucin

Monoclonal antibody-mediated binding to the tumor-specific NPC-1 epitope of MUC5AC, leading to immune-mediated tumor cell lysis via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).