title: Lentiviral vector followed by protein immunisation breaks tolerance against the self-antigen Her1 and results in lung cancer immunotherapy.
abstract: BACKGROUND
  Lung cancer remains a leading cause of cancer mortality, and so the aim of the present study was to develop a therapeutic vaccine protocol.
  
  
  METHODS
  We constructed a lentiviral vector (LV) expressing the extracellular domain (ECD) of murine Her1, an antigen associated with poor prognosis in lung cancer.
  
  
  RESULTS
  A single LV injection, followed by two Her1 protein boosts, was effective in reducing the metastatic burden of Lewis lung carcinoma in mice. The Her1 LV immunisation generated CD8+ T cells that recognised Her1 ECD presented by dendritic cells, and that also homed to Her1-expressing tumours. Protein boosting further increased the CD8+ T cell response and generated anti-Her1 antibodies; in the antibody response, Her1 LV priming increased Th1-dependent immunoglobulin G2c production.
  
  
  CONCLUSIONS
  The ability of this vaccine protocol to break both T cell and B cell tolerance to a self-antigen likely explains its effectiveness.
authors.affiliation: Centre of Molecular Immunology (CIM), Havana, Cuba.
authors.forename: Yeranddy Aguiar
authors.initials: YA
authors.lastname: Alpizar
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Karwacz
authors.forename: Frederick
authors.initials: F
authors.lastname: Arce
authors.forename: Arianna
authors.initials: A
authors.lastname: Yglesias Rivera
authors.forename: Luis Enrique
authors.initials: LE
authors.lastname: Fernández
authors.forename: Mary K
authors.initials: MK
authors.lastname: Collins
authors.forename: Belinda
authors.initials: B
authors.lastname: Sánchez Ramírez
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D018827:Carcinoma, Lewis Lung / Q000276:immunology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005822:Genetic Vectors / Q000235:genetics; D007108:Immune Tolerance / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D016086:Lentivirus; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control*
chemical_list: D000906:Antibodies; D019496:Cancer Vaccines; D066246:ErbB Receptors