title: Vaccines as early therapeutic interventions for cancer therapy: neutralising the immunosuppressive tumour environment and increasing T cell avidity may lead to improved responses.
abstract: BACKGROUND
  Considerable progress has been made in identifying the antigens recognised by the immune system. This has led to the success of monoclonal antibody therapy and the recent approval of prophylactic vaccines that give excellent protection against cervical cancer. Provenge will shortly be the first therapeutic vaccine to be approved.
  
  
  METHODS
  Our aim is to discuss the recent success with prophylactic cancer vaccines for prevention of cancer and the progress with therapeutic vaccines design to eradicate established tumours. Therapeutic vaccines need to stimulate high-avidity T cell responses that can recognise and kill tumours. How this can be achieved in cancer patients is discussed. The immunosuppressive tumour environment also needs to be modified to allow extravasation and efficacy of the vaccine induced T cells.
  
  
  RESULTS
  An insight into the limitations of present cancer vaccine approaches and how they can be manipulated to give more effective anti-tumour responses.
  
  
  CONCLUSIONS
  A combination of more effective vaccines that stimulate high-avidity T cells, in combination with drugs or monoclonal antibodies that neutralize immunosuppressive factors within the tumour environment are needed to improve the efficacy of immunotherapy of cancer.
authors.affiliation: Academic Department of Clinical Oncology, City Hospital, University of Nottingham, Hucknall Road, Nottingham NG5 1PB, UK. lindy.durrant@nottingham.ac.uk
authors.forename: Lindy G
authors.initials: LG
authors.lastname: Durrant
authors.forename: Victoria
authors.initials: V
authors.lastname: Pudney
authors.forename: Ian
authors.initials: I
authors.lastname: Spendlove
authors.forename: Rachael Louise
authors.initials: RL
authors.lastname: Metheringham
mesh_terms: D000818:Animals; D019496:Cancer Vaccines / Q000627:therapeutic use*; D006801:Humans; D007108:Immune Tolerance; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology*; D016896:Treatment Outcome; D019139:Tumor Escape
chemical_list: D019496:Cancer Vaccines