Sialylated N-linked glycans

Sialylated N-linked glycans are complex carbohydrate structures attached to cell surface proteins, characterized by terminal N-acetylneuraminic acid (Neu5Ac) residues. In the context of oncology, many tumors exhibit hypersialylation, which creates a glyco-immune checkpoint that suppresses the immune response by binding to inhibitory Siglec receptors on immune cells such as natural killer (NK) cells and macrophages (Varki, 2008; Zhou et al., 2020). This interaction effectively signals self-recognition and prevents the immune system from attacking the tumor. Therapeutic strategies targeting these glycans, such as the sialidase fusion protein E-602, work by enzymatically removing the terminal sialic acids to create desialylated N-glycans (Gray et al., 2020; Palleon Pharmaceuticals). This process disrupts the inhibitory signaling pathway and exposes underlying glycan structures, thereby restoring the ability of the immune system to recognize and eliminate cancer cells (Läubli & Varki, 2020).

Other names

Cell surface N-linked glycans with terminal N-acetylneuraminic acidSialic acid-terminated N-glycansNeu5Ac-N-glycansSiglec ligandsGlyco-immune checkpoint ligandsDesialylated N-glycans (as therapeutic product)

Enzymatic removal of terminal N-acetylneuraminic acid (sialic acid) residues from N-linked glycans to disrupt the sialic acid-Siglec immune checkpoint axis and enhance anti-tumor immunity.