Lentivirally transduced dendritic cells as a tool for cancer immunotherapy

J Gene Med. 2003 Aug;5(8):654-67. doi: 10.1002/jgm.400.


Background: Dendritic cells (DC) are the professional antigen-presenting cells of the immune system, fully equipped to prime naive T cells and thus essential components for cancer immunotherapy.

Methods: We tested the influence of several elements (cPPT, trip, WPRE, SIN) on the transduction efficiency of human DC. Human and murine DC were transduced with tNGFR-encoding lentiviruses to assess the effect of transduction on phenotype and function. Human DC were transduced with lentiviruses encoding huIi80MAGE-A3 and murine DC with huIi80tOVA to test antigen presentation.

Results: A self-inactivating (SIN) lentiviral vector containing the trip element was most efficient in transducing human DC. The transduction of DC with trip/SIN tNGFR encoding lentiviral vectors at MOI 15 resulted in stable gene expression in up to 94.6% (murine) and 88.2% (human) of the mature DC, without perturbing viability, phenotype and function. Human huIi80MAGE-A3-transduced DC were able to stimulate MAGE-A3-specific CD4(+) and CD8(+) T cell clones and could prime both MAGE-A3-specific CD4(+) and CD8(+) T cells in vitro. Murine huIi80tOVA-transduced DC were able to present OVA peptides in the context of MHC class I and class II in vitro and induced a strong OVA-specific cytotoxic T lymphocyte response in vivo, that was protective against subsequent challenge with OVA-expressing tumor cells.

Conclusions: We show that, using lentiviral vectors, efficient gene transfer in human and murine DC can be obtained and that these DC can elicit antigen-specific immune responses in vitro and in vivo. The composition of the transfer vector has a major impact on the transduction efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation
  • Antigens, Neoplasm / immunology
  • Antigens, Neoplasm / metabolism
  • Cell Line
  • Dendritic Cells / physiology*
  • Dendritic Cells / virology
  • Female
  • Gene Transfer Techniques*
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Interleukin-12 / metabolism
  • Lentivirus / genetics*
  • Lentivirus / metabolism
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Neoplasm Proteins*
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Survival Rate
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transduction, Genetic*


  • Antigens, Neoplasm
  • MAGEA3 protein, human
  • Mageb3 protein, mouse
  • Neoplasm Proteins
  • Interleukin-12