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Use of a lentiviral flap vector for induction of CTL immunity against melanoma. Perspectives for immunotherapy
Author(s) -
Firat Hüseyin,
Zennou Véronique,
GarciaPons Francisco,
Ginhoux Florent,
Cochet Madeleine,
Danos Olivier,
Lemonnier François A.,
LangladeDemoyen Pierre,
Charneau Pierre
Publication year - 2002
Publication title -
the journal of gene medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.689
H-Index - 91
eISSN - 1521-2254
pISSN - 1099-498X
DOI - 10.1002/jgm.243
Subject(s) - ctl* , ex vivo , transduction (biophysics) , biology , viral vector , cytotoxic t cell , priming (agriculture) , recombinant dna , virology , genetic enhancement , immunotherapy , vector (molecular biology) , immunology , in vivo , cancer research , immune system , cd8 , gene , in vitro , genetics , biochemistry , germination , botany
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. Conclusion 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. Copyright © 2002 John Wiley & Sons, Ltd.