The immune response to Thomsen-Friedenreich disaccharide, and glycan engineering.

FERNANDO JOSE IRAZOQUI; SENDRA VG,; LARDONE RD,; NORES GA.,

IMMUNOLOGY AND CELL BIOLOGY

Año: 2005 vol. 83 p. 405 - 412

0818-9641

© 2005 Australasian Society for Immunology Inc. Immune response to Thomsen–Friedenreich disaccharide and glycan engineering FERNANDO J IRAZOQUI, VICTOR G SENDRA, RICARDO D LARDONE and GUSTAVO A NORES CIQUIBIC-CONICET/Department of Biological Chemistry, Faculty of Chemical Sciences, National University of Cordoba, Ciudad Universitaria, Cordoba, Argentina 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ﾀ1-3GalNAcｿ-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. 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. overexpression of the uncovered Galﾀ1-3GalNAcｿ-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. 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. O-glycan backbone and core regions. Epithelial tumour cells typically show overexpression of the uncovered Galﾀ1-3GalNAcｿ-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. 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. ﾀ1-3GalNAcｿ-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.