Prophylactic Dendritic Cell-Based Vaccines Efficiently Inhibit Metastases in Murine Metastatic Melanoma

PLoS One. 2015 Sep 1;10(9):e0136911. doi: 10.1371/journal.pone.0136911. eCollection 2015.

Abstract

Recent data on the application of dendritic cells (DCs) as anti-tumor vaccines has shown their great potential in therapy and prophylaxis of cancer. Here we report on a comparison of two treatment schemes with DCs that display the models of prophylactic and therapeutic vaccination using three different experimental tumor models: namely, Krebs-2 adenocarcinoma (primary tumor), melanoma (B16, metastatic tumor without a primary node) and Lewis lung carcinoma (LLC, metastatic tumor with a primary node). Dendritic cells generated from bone marrow-derived DC precursors and loaded with lysate of tumor cells or transfected with the complexes of total tumor RNA with cationic liposomes were used for vaccination. Lipofectamine 2000 and liposomes consisting of helper lipid DOPE (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine) and cationic lipid 2D3 (1,26-Bis(1,2-de-O-tetradecyl-rac-glycerol)-7,11,16,20-tetraazahexacosan tetrahydrocloride) were used for RNA transfection. It was shown that DCs loaded with tumor lysate were ineffective in contrast to tumor-derived RNA. Therapeutic vaccination with DCs loaded by lipoplexes RNA/Lipofectamine 2000 was the most efficient for treatment of non-metastatic Krebs-2, where a 1.9-fold tumor growth retardation was observed. Single prophylactic vaccination with DCs loaded by lipoplexes RNA/2D3 was the most efficient to treat highly aggressive metastatic tumors LLC and B16, where 4.7- and 10-fold suppression of the number of lung metastases was observed, respectively. Antimetastatic effect of single prophylactic DC vaccination in metastatic melanoma model was accompanied by the reductions in the levels of Th2-specific cytokines however the change of the levels of Th1/Th2/Th17 master regulators was not found. Failure of double prophylactic vaccination is explained by Th17-response polarization associated with autoimmune and pro-inflammatory reactions. In the case of therapeutic DC vaccine the polarization of Th1-response was found nevertheless the antimetastatic effect was less effective in comparison with prophylactic DC vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cancer Vaccines / immunology*
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / metabolism
  • Carcinoma, Lewis Lung / pathology
  • Cell Line, Tumor
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / pathology
  • Liposomes / chemistry
  • Lung Neoplasms / immunology
  • Lung Neoplasms / pathology
  • Male
  • Melanoma, Experimental / immunology*
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Metastasis / immunology*
  • Neoplasm Metastasis / pathology
  • Phosphatidylethanolamines / chemistry
  • Transfection / methods
  • Vaccination / methods

Substances

  • Cancer Vaccines
  • Cytokines
  • Liposomes
  • Phosphatidylethanolamines
  • 1,2-dielaidoylphosphatidylethanolamine

Grants and funding

This research was supported by the Russian Academy of Science under the programs “Molecular and Cellular Biology”; Interdisciplinary grant of SB RAS no. 86, by the grant Scientific schools SS-01350.2014.4, and Special Purpose Program “Research and Development in a Priority Direction of Development of a Scientific and Technological Complex of Russia for 2014–2020” (Agreement No. 14.607.21.0043, project RFMEFI60714X0043). MOV was a recipient of Presidential fellowship 1619.2013.4.