Therapeutic Targeting of Siglecs using Antibody- and Glycan-Based Approaches

The sialic acid-binding immunoglobulin-like lectins (Siglecs) are a family of immunomodulatory receptors whose functions are regulated by their glycan ligands. Siglecs are attractive therapeutic targets because of their cell type-specific expression pattern, endocytic properties, high expression on certain lymphomas/leukemias, and ability to modulate receptor signaling. Siglec-targeting approaches with therapeutic potential encompass antibody- and glycan-based strategies. Several antibody-based therapies are in clinical trials and continue to be developed for the treatment of lymphoma/leukemia and autoimmune disease, while the therapeutic potential of glycan-based strategies for cargo delivery and immunomodulation is a promising new approach. Here we review these strategies with special emphasis on emerging approaches and disease areas that may benefit from targeting the Siglec family.

TrendsSiglecs are attractive therapeutic targets due to their restricted expression pattern.The endocytic and immunomodulatory properties of Siglecs can be exploited.Numerous antibody-based therapies targeting Siglecs are in clinical development.Glycan ligands of Siglecs are effective for cargo delivery and functional modulation.