Globo H hexasaccharide (Globo H)

Globo H (Fucα1→2Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glc) is a hexasaccharide glycosphingolipid that serves as a prominent tumor-associated carbohydrate antigen (TACA) [PMID: 29151134]. It is significantly overexpressed on the surface of various epithelial tumors, such as breast, prostate, and pancreatic cancers, while its expression in normal tissues is restricted to the apical surface of secretory cells, which are relatively sequestered from the immune system [PMID: 24105577]. This specific expression pattern makes Globo H an ideal target for various immunotherapeutic approaches, including vaccines, monoclonal antibodies, and antibody-drug conjugates (ADCs) [PMID: 32661316]. For instance, the vaccine Adagloxad simolenin (OBI-822) is designed to induce high titers of anti-Globo H IgG antibodies to trigger complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated cytotoxicity (ADCC) against tumor cells [PMID: 27363551]. Other developments include OBI-888, a humanized monoclonal antibody, and OBI-999, an ADC that delivers a cytotoxic payload specifically to Globo H-positive cells [ClinicalTrials.gov: NCT03573245]. Despite its promise, challenges include the low immunogenicity of carbohydrate antigens, which often requires conjugation to carrier proteins like Keyhole Limpet Hemocyanin (KLH) and the use of potent adjuvants [PMID: 23838315]. Its role in promoting tumor cell survival and angiogenesis further underscores its importance as a therapeutic target in oncology [PMID: 26109502].

Other names

Globo H ceramideGHeFucα1→2Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4GlcTumor-associated carbohydrate antigen Globo H

Induction of humoral immune response via active immunization with carbohydrate-protein conjugates; passive immunotherapy using monoclonal antibodies to trigger ADCC and CDC; and targeted delivery of cytotoxic agents via antibody-drug conjugates.