title: The CD4-like molecule LAG-3, biology and therapeutic applications.
abstract: BACKGROUND
  Promising immunotherapeutic agents targeting co-stimulatory pathways are currently being tested in clinical trials. One player in this array of regulatory pathways is the LAG-3/MHC class II axis. The lymphocyte activation gene-3 (LAG-3) is a negative co-stimulatory receptor that modulates T cell homeostasis, proliferation and activation. A recombinant soluble dimeric form of LAG-3 (sLAG-3-Ig, IMP321) shows adjuvant properties and enhances immunogenicity of tumor vaccines. Recent clinical trials produced encouraging results, especially when the human dimeric soluble form of LAG-3 (hLAG-3-Ig) was used in combination with chemotherapy.
  
  
  METHODS
  The biological relevance of LAG-3 in vivo. Pre-clinical data demonstrating adjuvant properties, as well as the improvement of tumor immunity by sLAG-3-Ig. Recent advances in the clinical development of the therapeutic reagent IMP321, hLAG-3-Ig, for cancer treatment.
  
  
  RESULTS
  This review summarizes preclinical and clinical data on the biological functions of LAG-3.
  
  
  CONCLUSIONS
  The LAG-3 inhibitory pathway is attracting attention, in the light of recent studies demonstrating its role in T cell unresponsiveness, and Treg function after chronic antigen stimulation. As a soluble recombinant dimer, the sLAG-3-Ig protein acts as an adjuvant for therapeutic induction of T cell responses, and may be beneficial to cancer patients when used in combination therapies.
authors.affiliation: Ludwig Institute for Cancer Research Ltd, Epalinges, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Sierro
authors.forename: Pedro
authors.initials: P
authors.lastname: Romero
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Speiser
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D009369:Neoplasms / Q000276:immunology; D012995:Solubility; D013601:T-Lymphocytes / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D019496:Cancer Vaccines; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human; C000720328:soluble LAG-3 protein, human