H-type 4 glycan (H4)

H-type 4 glycan, most commonly recognized in its hexasaccharide form as Globo-H (Fucα1-2Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc), is a prominent tumor-associated carbohydrate antigen (TACA) belonging to the globo-series glycolipids [PMID: 24510883]. It is characterized by the terminal H-type 4 linkage (Fucα1-2Galβ1-3GalNAcβ), which distinguishes it from other H-antigen types found in the ABO blood group system [Essentials of Glycobiology, 4th edition]. While expression in normal adult tissues is highly restricted to the apical surface of epithelial cells in secretory organs—sites typically sequestered from the immune system—it is significantly overexpressed on the surface of various epithelial cancers, including breast, prostate, lung, and ovarian malignancies [PMID: 29158355]. This differential expression profile makes H-type 4 glycan an attractive target for cancer immunotherapies, such as the synthetic glycan vaccine Adagloxad simolenin (OBI-822) and the humanized monoclonal antibody OBI-888 [ClinicalTrials.gov, NCT03562637]. These therapeutic strategies aim to exploit the glycan's presence to trigger immune-mediated destruction of tumor cells via mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) [PMID: 30356154].

Other names

Globo-HH-type 4 antigenFuc-alpha-1,2-Gal-beta-1,3-GalNAc-betaGlobo-H hexasaccharideFucα1-2Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc

Targeting of tumor-associated carbohydrate antigens via active immunization (vaccines) or passive immunotherapy (monoclonal antibodies) to induce antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against malignant cells.