Tumor-associated sialylated glycans (TASGs)

Tumor-associated sialylated glycans (TASGs) are a diverse group of carbohydrate structures that are aberrantly overexpressed on the surface of malignant cells, a hallmark of cancer known as hypersialylation (Büll et al., 2014). These glycans, including Sialyl-Lewis X (sLeX), Sialyl-Tn (sTn), and gangliosides like GD2 and GD3, are integral to the tumor's ability to invade tissues and metastasize by facilitating interactions with selectins on endothelial cells (Heimburg-Molinaro et al., 2011). Beyond structural roles, TASGs function as potent immune modulators by serving as ligands for Sialic acid-binding immunoglobulin-type lectins (Siglecs) found on various immune cells, effectively creating a glyco-immune checkpoint that shields the tumor from immune destruction (Zhou et al., 2020). Therapeutic interventions targeting TASGs are a rapidly evolving field, encompassing monoclonal antibodies like Dinutuximab that trigger antibody-dependent cellular cytotoxicity (ADCC), CAR-T cells directed at specific gangliosides, and innovative sialidase-based therapies like E-602 that enzymatically strip sialic acids to re-sensitize the tumor to the immune system (Palleon Pharmaceuticals, 2023; FDA, 2015). By disrupting the Sialic acid-Siglec axis, these therapies aim to restore the activity of natural killer (NK) cells and macrophages within the tumor microenvironment. Furthermore, TASGs like CA19-9 serve as critical clinical biomarkers for monitoring disease progression and treatment efficacy in various solid tumors.

Other names

Sialylated tumor-associated carbohydrate antigensTACAsSialyl-glycansHypersialylated cancer cell surface glycansSialic acid-containing glycansSialyl-Lewis antigensTumor-associated gangliosides

Sialic acid-Siglec axis inhibition; Antibody-dependent cellular cytotoxicity (ADCC); Complement-dependent cytotoxicity (CDC); Enzymatic desialylation of the tumor cell surface; Inhibition of selectin-mediated metastasis