Globo H tumor-associated carbohydrate antigen (Globo H)

Globo H is a hexasaccharide (Fucα1→2Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glc) that belongs to the globo-series of glycosphingolipids and serves as a prominent tumor-associated carbohydrate antigen (TACA) [1, 4]. It is overexpressed on the outer membrane of various epithelial cancers, including breast, prostate, lung, pancreatic, and gastric tumors, while its expression in normal tissues is restricted to the apical surface of epithelial cells in secretory organs [1, 2, 7]. Biologically, Globo H facilitates tumor progression by promoting cell adhesion, migration, and angiogenesis, and it contributes to immune evasion by inhibiting Notch 1 signaling in immune cells [5, 6, 8]. Because of its high tumor specificity and role in malignancy, Globo H is a major target for cancer immunotherapies, including vaccines like Adagloxad simolenin (OBI-822) that induce humoral immunity, and antibody-drug conjugates (ADCs) like OBI-999 that deliver cytotoxic payloads [1, 3, 9]. Clinical trials utilize Globo H expression levels as a biomarker for patient selection, aiming to improve outcomes in patients with high-expressing refractory solid tumors [5, 9, 10].

Other names

GlobohexaosylceramideGHCerBG-HFuc-Gal-GalNAc-Gal-Gal-GlcGlobo H hexasaccharide

Active immunization inducing anti-Globo H IgG and IgM antibodies; Antibody-dependent cellular cytotoxicity (ADCC); Complement-dependent cytotoxicity (CDC); Targeted delivery of cytotoxic payloads (e.g., MMAE) via antibody-drug conjugates; Inhibition of Notch 1 signaling to reverse immunosuppression; Inhibition of tumor cell adhesion and angiogenesis.