title: Immuno-regulatory antibodies for the treatment of cancer.
abstract: BACKGROUND
  After years of limited success, progress of anti-cancer immuno-therapeutics has been considerable over the past decade. Key to this progress has been the application of new biological insights around the importance and nature of immune checkpoints that are able to reverse down-regulation of anti-tumor immunity.
  
  
  METHODS
  An overview of the preclinical and recent clinical trial data on key immuno-regulatory agents currently in development, including antibody targeting of cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed death receptor 1 (PD-1) on T-lymphocytes and its principal ligand (PD-L1) on tumor cells as well as immune agonists (e.g., anti-CD40).
  
  
  CONCLUSIONS
  Durable long-term responses in some patients with advanced melanoma, initially with ipilimumab (anti-CTLA-4) and more recently antibodies targeting either PD-1 or PD-L1 in patients with melanoma and renal cancer, non-small-cell lung, bladder and head and neck cancers with less toxicity, have provided real optimism that immunotherapeutic approaches can improve outcomes in a wide range of cancer. The manageable tolerability of PD-1-pathway blockers and their unique mechanism of action are encouraging combination approaches. Current efforts focus on registration trials of single agents plus combinations in many different tumor types and treatment settings and identifying and developing predictive biomarkers of immunological response.
authors.affiliation: Targeted Therapy Group, Institute of Cancer Sciences, University of Manchester, The Christie Hospital, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre , Manchester M20 4BX , UK +44 0 161 446 8110 ; +44 0 161 446 8001 ; tmi@Manchester.ac.uk.
authors.forename: Jamie
authors.initials: J
authors.lastname: Honeychurch
authors.forename: Eleanor J
authors.initials: EJ
authors.lastname: Cheadle
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Dovedi
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Illidge
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D060908:CTLA-4 Antigen / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000639:trends*; D000074324:Ipilimumab; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D060908:CTLA-4 Antigen; D000074324:Ipilimumab; D061026:Programmed Cell Death 1 Receptor
keywords: CD40; cytotoxic T-lymphocyte antigen 4; immune checkpoint inhibitors; immunotherapy; mAb; programmed death receptor 1; programmed death receptor 1 ligand