Cancer prevention with semi-allogeneic ES cell-derived dendritic cells

Biochem Biophys Res Commun. 2005 Sep 16;335(1):5-13. doi: 10.1016/j.bbrc.2005.06.096.

Abstract

Dendritic cells (DC) genetically modified to present tumor-associated antigen are a promising means for anti-cancer immunotherapy. By introducing expression vectors into ES cells and subsequently inducing differentiation to DC (ES-DC), we can generate transfectant DC expressing the transgenes. In the future clinical application of this technology, the unavailability of human ES cells genetically identical to the patients will be a problem. However, in most cases, semi-allogeneic ES cells sharing some of HLA alleles with recipients are expected to be available. In the present study, we observed that model tumor antigen (OVA)-expressing mouse ES-DC transferred into semi-allogeneic mice potently primed OVA-reactive CTL and elicited a significant protection against challenge with OVA-expressing tumor. Genetic modification of ES-DC to overexpress SPI-6, the specific inhibitor of granzyme B, further enhanced their capacity to prime antigen-specific CTL in semi-allogeneic recipient mice. These results suggest the potential of ES-DC as a novel means for anti-cancer immunotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens / genetics
  • Antigens / immunology
  • Cell Differentiation*
  • Cell Line
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / transplantation
  • Immunotherapy
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Neoplasms / genetics
  • Neoplasms / immunology
  • Neoplasms / metabolism
  • Neoplasms / prevention & control*
  • Ovalbumin / genetics
  • Ovalbumin / immunology
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism
  • Serpins / genetics
  • Serpins / metabolism
  • Stem Cell Transplantation
  • Stem Cells / cytology*
  • Survival Rate
  • T-Lymphocytes, Cytotoxic / immunology
  • Xenograft Model Antitumor Assays

Substances

  • Antigens
  • Membrane Proteins
  • Serpins
  • Ovalbumin
  • Serine Endopeptidases
  • Serpinb9 protein, mouse