The role of Globo H and SSEA-4 in the Development and Progression of Cancer, and their Potential as Therapeutic Targets

Abstract

Glycans, chains of sugar molecules found conjugated to cell proteins and lipids, contribute to their growth, movement and differentiation. Aberrant glycosylation is a hallmark of several medical conditions including tumorigenesis. Glycosphingolipids (GSLs), consisting of glycans conjugated to a lipid (ceramide) core, are found in the lipid bilayer of eukaryotic cell membranes. GSLs, play an active role in cell processes. Several GSLs are expressed by human embryonic stem cells and have been found to be overexpressed in several types of cancer. In this review, we discuss the data, hypotheses and perspectives related to the GSLs Globo H and SSEA-4.

Efficacy and safety of glycosphingolipid SSEA-4 targeting CAR-T cells in an ovarian carcinoma model

“…Confirming previous results (Sigal et al ., 2022), SSEA-4 expression was detected in most of the cases of ovarian, pancreatic, and gastric cancer tissues. Based on the positive SSEA-4 expression in several cancer types, anti-SSEA-4 CAR-T cells were generated and functionally characterized for specific and effective anti-tumor response and safety.…”

“…SSEA-4 expression has been demonstrated in various types of cancer (Sigal et al , 2022). To corroborate and extend previous findings, we stained formalin-fixed paraffin-embedded (FFPE) clinical gastric cancer samples.…”

Carrier diversity and chemical ligations in the toolbox for designing tumor-associated carbohydrate antigens (TACAs) as synthetic vaccine candidates

“…The Globo-H antigen was initially called the MBr1 antigen and has been clearly identified in several tumors and triple-negative breast cancer in particular. 124 Again, Danishefsky et al successfully prepared several variants of the Globo-H conjugates that resulted in clinical trials. In their first synthesis, the authors used an allyl glycoside-ending Globo-H derivative (78) as a precursor for the attachment to KLH (Scheme 11).…”

“…The immunogenicity of the TLR2 ligand glycopeptide TACAvaccines (122)(123)(124) was evaluated in Balb/c-J mice using complete Freund's adjuvant (CFA). Booster immunizations with incomplete Freund's adjuvant (IFA) were performed after every 20 days.…”

“…Detailed biosynthesis also showed how the Lacto-, Ganglio-, and Globo-series are inter-related. 124 Of particular interest in this regard is the close structural similarity between the hexasaccharide Globo-H antigen (see Scheme 11) and its close analogy to the stage-specific embryonic antigen-4 SSEA-4 which only differs by the replacement of the fucose residue by sialic acid. The Globo-H antigen was initially called the MBr1 antigen and has been clearly identified in several tumors and triple-negative breast cancer in particular.…”