Cell-surface carbohydrate motif

Cell-surface carbohydrate motifs, or glycans, are complex oligosaccharides covalently attached to proteins and lipids on the exterior of the cell membrane. These motifs form the glycocalyx and are essential for mediating cell-cell recognition, adhesion, and communication by interacting with carbohydrate-binding proteins such as lectins and selectins [1, 2]. In pathological states like cancer, aberrant glycosylation leads to the presentation of tumor-associated carbohydrate antigens (TACAs), which facilitate tumor progression, metastasis, and evasion of the host immune system [2, 3]. Because these motifs are often differentially expressed on diseased versus healthy cells, they serve as valuable targets for immunotherapy, including monoclonal antibodies and glycan-based vaccines [4]. For instance, targeting the ganglioside GD2 has proven effective in treating neuroblastoma by inducing immune-mediated cell death [4, 5]. Beyond oncology, these motifs are critical for pathogen entry, as many viruses and bacteria utilize specific host glycans to attach to and infect cells [1, 6]. Therapeutic strategies targeting these motifs include the use of antibodies to trigger antibody-dependent cellular cytotoxicity (ADCC) and the development of conjugate vaccines to overcome the low immunogenicity of pure carbohydrates [5, 6]. However, therapeutic development is complicated by the inherent structural diversity of glycans and the risk of off-target effects if the targeted motif is also present on vital normal tissues [5]. References: [1] Varki A, et al. Essentials of Glycobiology (2015). [2] Pinho SS, Reis CA. Nat Rev Cancer (2015). [3] Munkley J, Elliott DJ. Oncotarget (2016). [4] Yu AL, et al. N Engl J Med (2010). [5] Zhou Z, et al. Angew Chem Int Ed Engl (2021). [6] Heimburg-Molinaro J, et al. Vaccine (2011).

Other names

GlycanCell-surface glycanTumor-associated carbohydrate antigenTACAGlyco-epitopeCell-surface oligosaccharide

Induction of antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), inhibition of ligand-receptor interactions, and stimulation of glycan-specific immune responses.