Dendritic cells strongly boost the antitumor activity of adoptively transferred T cells in vivo

Cancer Res. 2004 Sep 15;64(18):6783-90. doi: 10.1158/0008-5472.CAN-04-1621.

Abstract

Dendritic cells (DCs) have been well characterized for their ability to initiate cell-mediated immune responses by stimulating naive T cells. However, the use of DCs to stimulate antigen-activated T cells in vivo has not been investigated. In this study, we determined whether DC vaccination could improve the efficacy of activated, adoptively transferred T cells to induce an enhanced antitumor immune response. Mice bearing B16 melanoma tumors expressing the gp100 tumor antigen were treated with cultured, activated T cells transgenic for a T-cell receptor specifically recognizing gp100, with or without concurrent peptide-pulsed DC vaccination. In this model, antigen-specific DC vaccination induced cytokine production, enhanced proliferation, and increased tumor infiltration of adoptively transferred T cells. Furthermore, the combination of DC vaccination and adoptive T-cell transfer led to a more robust antitumor response than the use of each treatment individually. Collectively, these findings illuminate a new potential application for DCs in the in vivo stimulation of adoptively transferred T cells and may be a useful approach for the immunotherapy of cancer.

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Dendritic Cells / immunology*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Lymphocyte Activation / immunology
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasm Proteins / immunology
  • Peptide Fragments / immunology
  • T-Lymphocytes / immunology*
  • gp100 Melanoma Antigen

Substances

  • Cancer Vaccines
  • Membrane Glycoproteins
  • Neoplasm Proteins
  • PMEL protein, human
  • Peptide Fragments
  • Pmel protein, mouse
  • gp100 Melanoma Antigen