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A DNA-based cancer vaccine enhances lymphocyte cross talk by engaging the nkg2d receptor

Academic Article
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Overview

authors

  • Zhou, H.
  • Luo, Y. P.
  • Kaplan, C. D.
  • Kruger, J. A.
  • Lee, S. H.
  • Xiang, R.
  • Reisfeld, Ralph

publication date

  • April 2006

journal

  • Blood  Journal

abstract

  • The NKG2D receptor is a stimulatory receptor expressed on NK cells and activated CD8 T cells. We previously demonstrated that engaging the NKG2D receptor markedly improved the efficacy of a survivin-based DNA vaccine. The combination vaccine, encoding both the NKG2D ligand H60 and survivin, activates innate and adaptive antitumor immunity and results in better protection against tumors of different origin and NKG2D expression levels. Here we demonstrate that the enhanced vaccine efficacy is in part attributable to increased cross talk between lymphocytes. Depletion of CD8 T cells during priming reduces the vaccine-induced activation of dendritic cells (DCs) and NK cell activity. Depletion of NK cells during priming leads to reduced DC activation and CTL activity. However, depletion of CD4 T cells results in the activation of DCs, NK cells, and CD8 T cells and enhances NK cell activity. The pH60/Survivin vaccine also increases DCs and NK cells but decreases CD4 T cell homing to Peyer patches, presumably as a result of changes in the homing receptor profile. Thus, by preferentially activating and attracting positive regulators and reducing negative regulators in Peyer patches, this dual-function DNA vaccine induces a microenvironment more suitable for NK cell activation and T cell priming.

subject areas

  • Animals
  • Antigen Presentation
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines
  • Dendritic Cells
  • Gene Expression Regulation
  • Inhibitor of Apoptosis Proteins
  • Killer Cells, Natural
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred BALB C
  • Microtubule-Associated Proteins
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily K
  • Neoplasms
  • Peyer's Patches
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Repressor Proteins
  • Vaccines, DNA
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Identity

PubMed Central ID

  • PMC1895756

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2005-10-4231

PubMed ID

  • 16368879
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Additional Document Info

start page

  • 3251

end page

  • 3257

volume

  • 107

issue

  • 8

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