Globo H glycolipid antigen (Globo H)

Globo H is a hexasaccharide glycosphingolipid (Fucα1→2Galβ1→3GalNAcβ1→3Galα1→4Galβ1→4Glcβ1→Cer) that serves as a prominent tumor-associated carbohydrate antigen (TACA) (Huang et al., 2013, PNAS) [1]. It is overexpressed on the outer cell membrane of various epithelial cancers, including breast, prostate, lung, and ovarian cancers (Zhang et al., 1997, Cancer Res) [2]. In contrast, its expression on normal tissues is highly restricted, primarily found on the apical surface of epithelial cells in secretory organs such as the pancreas and salivary glands (OBI Pharma) [3]. This differential expression pattern makes it an attractive target for selective cancer therapies. In the context of malignancy, Globo H is thought to play roles in promoting tumor cell survival, migration, and angiogenesis (Chang et al., 2015) [4]. Therapeutic strategies targeting Globo H include active immunotherapy via carbohydrate-based vaccines, such as Adagloxad simolenin (OBI-822), which are designed to stimulate the patient's immune system to produce anti-Globo H antibodies (ClinicalTrials.gov) [5]. Additionally, passive immunotherapy approaches using humanized monoclonal antibodies (e.g., OBI-888) and antibody-drug conjugates (e.g., OBI-999) are being developed to directly target and kill Globo H-expressing cells (OBI Pharma) [3]. These interventions leverage mechanisms like antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) to eliminate tumor cells. Clinical development of these agents focuses on patients whose tumors show high Globo H expression as determined by immunohistochemistry.

Other names

Globo H ceramideMBr1 antigenFucα1-2Galβ1-3GalNAcβ1-3Galα1-4Galβ1-4Glc-CerTumor-associated carbohydrate antigen Globo H

Induction of a humoral immune response through active vaccination, or direct tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), and targeted delivery of cytotoxic payloads using antibody-drug conjugates.