Induction of effective therapeutic antitumor immunity by direct in vivo administration of lentiviral vectors

M Dullaers, S Van Meirvenne, C Heirman, L Straetman, A Bonehill, J L Aerts, K Thielemans, K Breckpot

Research output: Contribution to journalArticle

Abstract

Ex vivo lentivirally transduced dendritic cells (DC) have been described to induce CD8+ and CD4+ T-cell responses against various tumor-associated antigens (TAAs) in vitro and in vivo. We report here that direct administration of ovalbumin (OVA) encoding lentiviral vectors caused in vivo transduction of cells that were found in draining lymph nodes (LNs) and induced potent anti-OVA cytotoxic T cells similar to those elicited by ex vivo transduced DC. The cytotoxic T-lymphocyte (CTL) response following direct injection of lentiviral vectors was highly effective in eliminating target cells in vivo up to 30 days after immunization and was efficiently recalled after a boost immunization. Injection of lentiviral vectors furthermore activated OVA-specific CD4+ T cells and this CD4 help was shown to be necessary for an adequate primary and memory CTL response. When tested in therapeutic tumor experiments with OVA+ melanoma cells, direct administration of lentiviral vectors slowed down tumor growth to a comparable extent with the highest dose of ex vivo transduced DC. Taken together, these data indicate that direct in vivo administration of lentiviral vectors encoding TAAs has strong potential for anticancer vaccination.

Original languageEnglish
Pages (from-to)630-640
Number of pages11
JournalGene Therapy
Volume13
Issue number7
DOIs
Publication statusPublished - Apr 2006

Keywords

  • Animals
  • Antigens, Tumor-Associated, Carbohydrate/immunology
  • CD4-Positive T-Lymphocytes/immunology
  • Cell Line, Tumor
  • Dendritic Cells/immunology
  • Female
  • Genetic Therapy/methods
  • Genetic Vectors/administration & dosage
  • Immunologic Memory
  • Immunotherapy/methods
  • Interferon-gamma/immunology
  • Lentivirus/genetics
  • Lymph Nodes/immunology
  • Lymphocyte Activation
  • Melanoma, Experimental
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Transplantation
  • Neoplasms/therapy
  • Ovalbumin/genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Cytotoxic/immunology
  • Transduction, Genetic/methods

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