The paired receptors TIGIT and DNAM-1 as targets for therapeutic antibodies

Hum Antibodies. 2017;25(3-4):111-119. doi: 10.3233/HAB-160307.

Abstract

One of the most exciting fields in modern medicine is immunotherapy, treatment which looks to harness the power of the immune system to fight disease. A particularly effective strategy uses antibodies designed to influence the activity levels of the immune system. Here we look at two receptors - TIGIT and DNAM-1 - which bind the same ligands but have opposite effects on immune cells, earning them the label `paired receptors'. Importantly, natural killer cells and cytotoxic T cells express both of these receptors, and in certain cases their effector functions are dictated by TIGIT or DNAM-1 signaling. Agonist and antagonist antibodies targeting either TIGIT or DNAM-1 present many therapeutic options for diseases spanning from cancer to auto-immunity. In this review we present cases in which the modulation of these receptors holds potential for the development of novel therapies.

Keywords: DNAM-1; NK cells; TIGIT; autoimmune disease; cancer; immunotherapy.

Publication types

  • Review

MeSH terms

  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Gene Expression Regulation
  • Humans
  • Immunotherapy / methods*
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / pathology
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / pathology
  • Protein Binding
  • Receptor Cross-Talk / immunology
  • Receptors, Immunologic / agonists
  • Receptors, Immunologic / antagonists & inhibitors
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology*
  • Signal Transduction
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology

Substances

  • Antigens, Differentiation, T-Lymphocyte
  • Antineoplastic Agents, Immunological
  • CD226 antigen
  • Receptors, Immunologic
  • TIGIT protein, human