Immune response to Thomsen–Friedenreich disaccharide and glycan engineering

Abstract

Summary Cancer-associated mucins show frequent alterations of their oligosaccharide chain profile, with a switch to unmask normally cryptic O-glycan backbone and core regions. Epithelial tumour cells typically show overexpression of the uncovered Gal β 1-3GalNAc α -O-Ser/Thr (Core 1) structure, known as the T antigen or the Thomsen-Friedenreich antigen, the oligosaccharide chain of which is called the Thomsen-Friedenreich disaccharide (TFD). T antigen expression has been associated with immunosuppression, metastasis dissemination, and the proliferation of cancer cells. Several different strategies have been used to trigger a specific immune response to TFD. Natural T antigen and synthetic TFD residues have low immunodominance. In the T antigen, flexibility of the glycosidic bond reduces the immunogenicity of the sugar residue. Enhanced rigidity should favour certain glycan conformations and thereby improve TFD immunotargeting. We propose the term 'glycan engineering' for this approach. Such engineering of TFD should reduce the flexibility of its glycan moiety and thereby enhance its stability, rigidity and immunogenicity.

Maturation of Recombinant Hepatitis B Virus Surface Antigen Particles

“…Recently, this was demonstrated in the literature with a peptide tumor antigen MUC1 28 and a disaccharide antigen. 29 Increased flexibility of the antigen was shown to be clearly associated with reduced immunogenicity in these studies. Maturation of the capsid on a slow time-scale (e.g., overnight or over days), involving disulfide bond formation, is common for the disulfidebonded capsid or nucleocapsid of different viruses.…”

Computational Screening of the Human TF-Glycome Provides a Structural Definition for the Specificity of Anti-Tumor Antibody JAA-F11

“…An established carbohydrate-based cancer marker is the Thomsen-Friedenreich (TF) antigen (Galβ1-3GalNAcα), which is typically found O -linked to serine or threonine residues. The TF antigen (also known as T antigen) has been associated with several human carcinomas, including those found in the pancreas, colon, and breast, and on this basis has been referred to as a pan-carcinoma marker[3], [4], [5], [6]. TF antigen is concealed from the immune system in normal adult tissues as a result of extension with larger glycan chains[5], [7].…”

Enzymatic and Chemoenzymatic Syntheses of Disialyl Glycans and Their Necrotizing Enterocolitis Preventing Effects

“…O-GalNAc glycan core-2 structure) and glycolipids, and also an important carbohydrate epitope involved in cell adhesion, signaling, fertilization, differentiation, development, and cancer metastasis. 25 The disialyl Ta tetrasaccharide (DSTa, 6 ) has two α2–6-linked Neu5Ac residues on neighboring monosaccharide units in the disaccharide core, mimicking the situation of the terminal tetrasaccharide component in human milk DSLNT ( 1 ). It will be interesting to test whether it has NEC-preventing effects.…”