Cell-surface sialic acid (Sia)

Cell-surface sialic acids are a family of nine-carbon acidic monosaccharides typically found at the terminal positions of N-linked and O-linked glycans on the cell surface [1]. These residues play a fundamental role in biological processes, including cell-cell recognition, signal transduction, and the regulation of the immune response through interactions with Sialic acid-binding immunoglobulin-type lectins (Siglecs) [2]. In the context of oncology, many tumors exhibit hypersialylation, a process where an overabundance of sialic acids creates a glycan shield that helps the tumor evade immune detection by engaging inhibitory Siglec receptors on T cells and NK cells [3]. Furthermore, sialic acids serve as essential attachment points for various pathogens, such as the influenza virus, which uses hemagglutinin to bind these residues for entry and requires their cleavage by neuraminidase for viral release [4]. Therapeutic interventions targeting these residues include sialidase fusion proteins, such as E-602, designed to desialylate the tumor microenvironment and neuraminidase inhibitors that prevent viral egress [5]. Consequently, cell-surface sialic acids represent a critical focal point for both immuno-oncology and anti-viral drug development [6]. Sources: [1] Varki A. Sialic acids in human health and disease. Trends Mol Med. 2008. [2] Crocker PR, et al. Siglecs and their roles in the immune system. Nat Rev Immunol. 2007. [3] Läubli H, Varki A. Sialic acids as mediators of cancer progression. Curr Opin Struct Biol. 2020. [4] von Itzstein M. The war against influenza: neuraminidase inhibitors. Nat Rev Drug Discov. 2007. [5] Palleon Pharmaceuticals. E-602 Sialidase Program. 2023. [6] Zhou X, et al. Sialic Acid-Siglec Axis as a Target for Cancer Immunotherapy. Trends in Cancer. 2020.

Other names

N-acetylneuraminic acidNeu5AcSialoglycansGlycan-bound sialic acidNeuraminic acidTerminal sialic acid residues

Enzymatic cleavage of terminal sialic acid residues (sialidases/neuraminidases), inhibition of viral neuraminidase to prevent viral release, and blockade of Siglec-sialic acid immune checkpoint interactions.