Globo H ceramide (Globo H) (Globo H)

Globo H ceramide (Globo H) is a hexasaccharide (Fucα1→2Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glc) belonging to the globo-series of glycosphingolipids, primarily found on the outer leaflet of the plasma membrane (Huang et al., 2013, PNAS). It is a well-characterized tumor-associated carbohydrate antigen (TACA) that is highly overexpressed in a variety of epithelial cancers, including breast, prostate, lung, and ovarian malignancies (Zhang et al., 1997, Int J Cancer). In contrast, its expression in normal adult tissues is limited to the apical surfaces of epithelial cells in secretory organs, which are generally inaccessible to the immune system, providing a favorable therapeutic window (Danishefsky et al., 2000, Angewandte Chemie). Therapeutic strategies targeting Globo H include active immunotherapy via synthetic vaccines like Adagloxad simolenin, as well as passive immunotherapy using monoclonal antibodies (e.g., OBI-888) and antibody-drug conjugates (e.g., OBI-999) (OBI Pharma, 2024). These treatments aim to leverage the immune system to recognize and eliminate Globo H-positive tumor cells or deliver potent cytotoxins directly to the tumor site. The presence of Globo H on the cell surface also plays a role in cell-cell recognition and adhesion, potentially contributing to the metastatic potential of cancer cells.

Other names

Globo H hexasaccharideGHLFucα1→2Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4GlcFuc-Gal-GalNAc-Gal-Gal-Glc-Cer

Active immunization to induce endogenous anti-Globo H antibodies, monoclonal antibody-mediated antibody-dependent cellular cytotoxicity (ADCC), and antibody-drug conjugate (ADC) mediated delivery of cytotoxic payloads (Huang et al., 2013; OBI Pharma, 2024).