Activated leukocyte cell adhesion molecule (CD166) fucosylated core 1 O-glycan epitope (CD166-fuc-O-glycan)

Activated leukocyte cell adhesion molecule (CD166), also known as ALCAM, is a transmembrane glycoprotein belonging to the immunoglobulin superfamily that mediates cell-cell adhesion through homophilic and heterophilic interactions. The fucosylated core 1 O-glycan epitope is a specific post-translational modification (Fucα1-2Galβ1-4GlcNAcβ1-3Galβ1-3GalNAc-Ser/Thr) that is aberrantly expressed on CD166 in various cancers, including uterine endometrial and ovarian carcinomas. This specific glycoform serves as a tumor-associated antigen, distinguishing malignant cells from normal tissues where CD166 may be present but lacks this specific glycosylation pattern. The monoclonal antibody HMMC-1 specifically targets this fucosylated core 1 O-glycan on CD166, leading to the inhibition of tumor cell proliferation and invasive growth. Mechanistically, binding to this epitope induces G1 phase cell cycle arrest and upregulates cyclin-dependent kinase inhibitors such as p16 and p21. Additionally, targeting this glyco-epitope can trigger immune-mediated destruction of cancer cells via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Given its role in cancer metastasis and its restricted expression profile, this glycan-modified CD166 represents a promising target for precision oncology and immunotherapy.

Other names

ALCAM fucosylated core 1 O-glycanHMMC-1 epitopeCD166 glyco-epitopeTumor-associated glyco-epitope on CD166

Binding to the glyco-epitope on CD166 induces G1 cell cycle arrest, increases expression of cyclin-dependent kinase inhibitors p16 and p21, and mediates antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).