title: Use of a lentiviral flap vector for induction of CTL immunity against melanoma. Perspectives for immunotherapy.
abstract: BACKGROUND
  A central triple-stranded DNA structure created during HIV-1 reverse transcription, the central flap, acts as a cis-active nuclear import determinant of the HIV-1 DNA genome. Insertion of the sequences responsible for formation of the central DNA flap into an HIV-1-derived vector strongly enhances its transduction efficiency.
  
  
  METHODS
  HIV-1 vectors with or without inclusion of the DNA flap and encoding the same melanoma polyepitope were constructed to transduce dendritic cells (DCs) and to evaluate their capacity for induction of melanoma-specific cytotoxic T-lymphocyte (CTL) responses ex vivo and in vivo.
  
  
  RESULTS
  HIV-1 vectors including the DNA flap transduced up to 100% of immature mouse and human DCs. Inoculation of HLA-A2.1 transgenic mice with this flap vector elicited vigorous and multi-specific long-term anti-melanoma CTL responses, whereas the parental vector lacking the flap sequence was less efficient. Furthermore, human DCs transduced ex vivo with the recombinant DNA flap vector displayed efficient multi-specific primary human CTL responses against melanoma.
  
  
  CONCLUSIONS
  Lentiviral vectors including the DNA flap should be powerful tools both for active immunization and for the ex vivo priming of CTL for tumor immunotherapy.
authors.affiliation: Unité d'Immunité Cellulaire Antivirale, CNRS, URA 1923, lbis rue de l'Internationale, BP60-91002 Evry Cédex, France. firat@genethon.fr
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Firat
authors.forename: Véronique
authors.initials: V
authors.lastname: Zennou
authors.forename: Francisco
authors.initials: F
authors.lastname: Garcia-Pons
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Madeleine
authors.initials: M
authors.lastname: Cochet
authors.forename: Olivier
authors.initials: O
authors.lastname: Danos
authors.forename: François A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Pierre
authors.initials: P
authors.lastname: Langlade-Demoyen
authors.forename: Pierre
authors.initials: P
authors.lastname: Charneau
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D006678:HIV; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014161:Transduction, Genetic / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm