Targeting siglecs--a novel pharmacological strategy for immuno- and glycotherapy

Biochem Pharmacol. 2011 Aug 15;82(4):323-32. doi: 10.1016/j.bcp.2011.05.018. Epub 2011 May 31.

Abstract

The immune system must be tightly held in check to avoid bystander tissue damage as well as autoreactivity caused by overwhelming immune reactions. A novel family of immunoregulatory, carbohydrate-binding receptors, the Siglecs (sialic acid binding immunoglobulin-like lectins), has received particular attention in light of their capacity to mediate cell death, anti-proliferative effects and to regulate a variety of cellular activities. Siglec receptors are mainly expressed on leukocytes in a cell type-specific and differentiation-dependent manner. Siglecs might potentially be exploited as targets of novel immune- and glycotherapeutics for cell-directed therapies in autoimmune and allergic diseases, as well as in haematologic malignancies. Here we present novel insights on structural and functional characteristics, expression patterns and evolutionary aspects of Siglecs and their ligands. Pharmacological strategies using Siglec agonistic cross-linking therapeutics, such as monoclonal or engineered antibodies, intravenous immunoglobulin (IVIG), or glycomimetics are discussed. Modulation of immune responses by targeting Siglecs using agonistic or antagonistic therapeutics may have important clinical implications and may pave the way for novel pharmacological avenues for the treatment of autoimmune and allergic diseases or for tumor immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Autoimmune Diseases / therapy*
  • Clinical Trials as Topic / methods
  • Drug Delivery Systems / methods*
  • Hematologic Diseases / immunology
  • Hematologic Diseases / metabolism
  • Hematologic Diseases / therapy
  • Humans
  • Immunotherapy / methods*
  • Immunotherapy / trends
  • Inflammation Mediators / agonists
  • Inflammation Mediators / pharmacology*
  • Inflammation Mediators / physiology
  • Lectins / agonists
  • Lectins / chemistry
  • Lectins / physiology*
  • Sialic Acid Binding Ig-like Lectin 2 / immunology
  • Sialic Acid Binding Ig-like Lectin 2 / metabolism
  • Sialic Acid Binding Ig-like Lectin 3
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Sialic Acids / agonists
  • Sialic Acids / chemistry
  • Sialic Acids / metabolism*

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD22 protein, human
  • CD33 protein, human
  • Inflammation Mediators
  • Lectins
  • Sialic Acid Binding Ig-like Lectin 2
  • Sialic Acid Binding Ig-like Lectin 3
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Sialic Acids