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DNA-based vaccines activate innate and adaptive antitumor immunity by engaging the nkg2d receptor

Academic Article
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Overview

authors

  • Zhou, H.
  • Luo, Y. P.
  • Lo, J. F.
  • Kaplan, C. D.
  • Mizutani, M.
  • Mizutani, N.
  • Lee, Jiing-Dwan
  • Primus, F. J.
  • Becker, J. C.
  • Xiang, R.
  • Reisfeld, Ralph

publication date

  • 2005

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • The interaction of NKG2D, a stimulatory receptor expressed on natural killer (NK) cells and activated CD8(+) T cells, and its ligands mediates stimulatory and costimulatory signals to these cells. Here, we demonstrate that DNA-based vaccines, encoding syngeneic or allogeneic NKG2D ligands together with tumor antigens such as survivin or carcinoembryonic antigen, markedly activate both innate and adaptive antitumor immunity. Such vaccines result in highly effective, NK- and CD8(+) T cell-mediated protection against either breast or colon carcinoma cells in prophylactic and therapeutic settings. Notably, this protection was irrespective of the NKG2D ligand expression level of the tumor cells. Hence, this strategy has the potential to lead to widely applicable and possibly clinically useful DNA-based cancer vaccines.

subject areas

  • Adaptation, Physiological
  • Animals
  • CD8-Positive T-Lymphocytes
  • Cancer Vaccines
  • Carcinoembryonic Antigen
  • Cell Line, Tumor
  • Female
  • HLA-A2 Antigen
  • Humans
  • Immunity, Innate
  • Inhibitor of Apoptosis Proteins
  • Killer Cells, Natural
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microtubule-Associated Proteins
  • Minor Histocompatibility Antigens
  • NK Cell Lectin-Like Receptor Subfamily K
  • Neoplasms, Experimental
  • Receptors, Immunologic
  • Receptors, Natural Killer Cell
  • Repressor Proteins
  • T-Lymphocytes, Cytotoxic
  • Vaccines, DNA
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Research

keywords

  • NK cells
  • NKG2D ligands
  • Peyer's patches
  • T cells
  • survivin
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Identity

PubMed Central ID

  • PMC1182421

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0502208102

PubMed ID

  • 16040807
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Additional Document Info

start page

  • 10846

end page

  • 10851

volume

  • 102

issue

  • 31

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