Siglec Related Therapies

Siglecs

Biological cells have glycan chains with sialic acid (also called N-acetylneuraminic acid) at the end covering their surface. In the human body, N-acetylneuraminic acid (Neu5Ac) is the most prevalent. Increased sialylation of cancer cells may improve interactions with immunomodulatory lectins and aid in cancer cells' immunological evasion. Customers could find a Microarray Platform at CD BioGlyco including Sialic Acid Microarray and Lectin Microarray Assay which will help their research in Siglec related therapies.

Fig.1 The structure schematic diagram of Siglec family members. (Jiang, et al., 2022)

Siglec Agonist

Most Siglecs are classified as inhibitory because they contain intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIM) and ITIM-like motifs in the cytoplasmic tail. While a few are activated and signal through adaptor proteins. After binding to Sia glycan, ITIM may be phosphorylated by Src family tyrosine kinases to create docking sites for SH2 domain-containing protein tyrosine phosphatases, SHP1, and SHP2. These phosphatases can inhibit signaling pathways triggering nearby, regulating different physiological responses depending on the cell type and the Siglec expressed. Siglec-4, Siglec-14, Siglec-15, and Siglec-16 do not have ITIM or ITIM-like motifs but can signal through DNAX activating protein (DAP)12 binding, so they are called activating Siglecs.

Fig.2 Siglec expression by different mononuclear phagocytes in steady state. (Lübbers, et al., 2018)

Strategies of Siglec Targeting

Siglecs have become significant therapeutic targets because they are crucial in the regulation of immune cells. Recent data suggests that by binding to cancer-related glycans on tumor cells, Siglec receptors aid in the evasion of anticancer immune responses. Now Siglec-Targeted Therapies are a hot direction for scientific research.

• Recent evidence suggests that Siglec receptors help evade antitumor immune responses by binding to cancer-related glycans on tumor cells.
• Heat-stable antigen or small cell lung cancer cluster 4 antigen (CD24) is a ligand for Siglec-10 on tumor-related macrophages (Tams) and induces inhibition of phagocytosis.
• Many melanocytes express high levels of ganglioside GD3, it interacts with Siglec-7 on NK cells to inhibit NK cells' killing activity ability.
• The limited expression of Siglec-8 on eosinophils and mast cells can be used as a therapeutic target for asthma and allergy.
• Siglec-15 is mainly expressed in osteoclasts, and it is a potential therapeutic target for osteoporosis.

Why Choose Us?

CD BioGlyco is interested in the research of siglec-related therapies. We have a top team of scientists and a service team to respond to inquiries from all over the world and meet their scientific needs on time. If you are interested in our services, please contact us for further information.

References:

1. Jiang, K.-Y.; et al. The intriguing roles of SIGLEC family members in the tumor microenvironment. Biomarker Research. 2022, 10(1).
2. Lübbers, J.; et al. Modulation of immune tolerance via SIGLEC-sialic acid interactions. Frontiers in Immunology. 2018, 9.